Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
Clinical Variants
N/A
Squamous Cell
Carcinoma (SCC)
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
sun exposure
immunosuppression
genetic conditions
Risk factors
Lab/Imaging
Treatment
Clinical
Complications
young adults
FH of MM or DN
UV light
rptd childhood sunburns
# (>50) & size (>5mm) of nevi
CN
PMH of MM
high SES
Skin types 1&2
latitude
DNA repair defects
immunosuppression
NM in middle-aged men;
LMM in older pts w/ chronic UVB
exposure & age spots;
ALM more common in dark/Asian
pts
Benign Nevi
Dysplastic Nevi
Congenital Nevi
Xeroderma
pigmentosum (XP)
N/A
b-raf mutations
N-ras mutations
Sunburn
N/A
Inflammation, erythema
Failed or incomplete
repair of thymine dimers
--> mutations in p53
(higher risk for nonmelanoma skin cancers)
N/A
New melanin (delayed tanning) formed when keratinocytes
release MSH in response to UVR; MSH binds MC1R on
melanocytes --> increased melanin production and proliferation
Ichthyosis
Psoriasis
N/A
mutations in filaggrin
(which binds to keratin)
causes
bundling/collapsing of
keratin fibers
Histology?
Endothelial swelling, decreased langerhans, neutrophil
recruitment, apoptotic keratinocytes (bright pink)
areas of hyperplasia (thickened stratum corneum,
epidermis, dermis)
Disease
Epidermolysis bullosa
(EB)
Clinical Variants
(General)
Defining Characteristics
blisters on hands and feet
Pathogenesis
Junctional
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Treatment
Complications
sometimes defects w/
collagen 17 or B4/a6
integrins
Severe scarring
Autoantibodies against
Collagen VII
Significant scarring
Autoantibodies against
BPAG1 and/or BPAG2
Autoantibodies against
BPAG2, laminins,
integrins
Pemphigus
Pemphigus vulgaris
Chronic dermatitis
Subacute dermatitis
Pemphigus foliaceus
Ectodermal Dysplasia
N/A
Albinism
N/A
Vitiligo
N/A
Keloid
Panniculitis
N/A
N/A
onychomycosis
N/A
Dermatitis
General
Acute dermatitis (eczema)
Immunosuppressants,
corticosteroids; new therapies
(tyrosine kinase inhibitors to
increase resistance to pemphigus
IgG)
Immunosuppressants,
corticosteroids
20% of children, 1% of
adults
"childhood eczema"; 2More common if parent has AD
3x more common now;
more developed
countries
Acne
Tinea versicolor
Contact Dermatitis
1. Irritant
2. Allergic (ACD)
Seborrheic Dermatitis
N/A
N/A
Venous insufficiency
Histology? Acanthotic
1. irritant - not allergic,
but burned/inflamed by
substance (occur in
anyone exposed)
2. Allergic - allergy
response (poison ivy,
does not occur in
everybody)
Patch testing
Possible scarring
Disease
Clinical Variants
Pityrosporum folliculitis
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
Diffuse folliculitis
Lab/Imaging
Treatment
Complications
Responds to anti-fungal tx
S. aureus, occlusion of
non-dermatologic areas
Topical Abs
Oral Abs (if extensive, recurrent)
Abscess formation
Bacterial folliculitis
Bacterial folliculitis
Risk factors
Hot/humid environment
AB use
Immunosuppressant
Hi sebum prod
Pseudomonas
aeruginosa
Clinical
Furuncle (smaller)
Furuncles/ Carbuncles
Carbuncle (larger!)
S. aureus, GAS
Increased incidence in
SE, day care settings
S. aureus
Childhood
Crowded areas
Heat/humidity
Clinical
Gram stain/Cx
Rare
Looks like spider bite, furuncle, abscesses, pyomyositis, cellulitis Bacterial infection caused by methicillin resistant S. aureus
CA-MRSA
Dermatophytosis
Verruca vulgaris
Filamentous fungi
(Microsporum,
Trichophyton,
Epidermophyton)
Often none
Humid/occluded skin
Common infection even
Atopy (eczema)
in healthy hosts
Immunodeficiency
TOPICAL STEROIDS
HPV 2, 4
VERY common
20% of kids have at
some time
HPV 1
Common in adults
Verruca (warts)
Condylomata acuminata
Filiform warts
Verruca plana
Verruca plantaris
Increased prevalence
as SSTI, furunculosis;
can cause infections in
Pts lack typical risk factors
pts typically lacking
RFs for MRSA
(hospital/prison/ sports)
HPV
Children
HIV
Sexually active young adults
(Shingles)
Clinical
Crush prep
Bx (rare)
Histology? Henderson-Patterson bodies (eosinophilic
inclusion bodies)
Clinical
Tzanck prep (cannot distinguish HSV from VZV)
Direct fluorescent antibody (CAN distinguish HSV from
VZV)
Viral culture
Bx (rare)
advancing age
immunosuppression
Stress!
Clinical
Tzanck prep
DFA (distinguish HSV from VZV)
Viral Cx
Bx (rare)
Clinical
Bx (rare)
DNA testing to determine type of HPV present
Often none
HIV
Organ transplantation
Paring
Cryosurgery
Podophyllin (topical chem agent)
Spontaneous resolution (can take up
to 2y)
Imiquimod
Canthardin (good for kids)
Liquid nitrogen
Curettage
Self-limited in immuno-competent
host
Oral antivirals for
immunocompromised/ recurrent or
severe episodes
dissemination
transmission of varicella (chicken
pox)
Scabies
N/A
Eryisipelas
N/A
Group A Strep
Other beta-hemolytic
strep
S. aureus (CA-MRSA)
Group A Strep
Polymicrobial
Gas gangrene
(myonecrosis)
N/A
Less common in
children
Aerobic + Anaerobic
bowel flora
Clostridium
perfringens
C. novyi
C. histolyticum
Early? Think GAS or
Clostridium
GI or female GU
surgery? Bowel flora
Clean procedure? Skin
flora
(S. aureus, Strep sp)
clindamycin
Unasyn (ampicillin + SulbactamIV)
GAS, S. aureus, or
anaerobic
streptococci
Superficial incisional
(subq space)
Surgical Site Infections
(SSI)
Mineral oil prep? Mites with oval gray eggs and fecal
pellets
Chronic
More common in
infants/ children/ elderly
Acute
Monomicrobial
NSAIDs
Diabetes
Venous insufficiency
Completely normal hosts
Abdominal Surgeries
Decubitus ulcers
Perianal ulcers
Bartholin abscess
IVDU
h/o severe penetrating trauma
or crush injuries
Usually bacteremic
30-60% mortality
Polymicrobial - Ampicillin,
clindamycin, and ciprofloxacin
Aggressive surgical debridement
XR shows edema and gas in soft tissue
PCN + clindamycin
Prophylactic superficial
antisepsis
Perioperative ABs
Incision & Drainage
Spontaneous (hematogenous)
gangrene from Clostridium
septicum in pts with GI
malignancies or neutropenia
Disease
Osteoporosis
Clinical Variants
N/A
Defining Characteristics
BMD T-score < -2.5, increased incidence of fractures
Pathogenesis
Etiologies
Loss of bone
trabeculae
(microarchitectural
deterioration)
Genetic predisposition
Estrogen deficiency
activates immune
response
Epidemiology
Risk factors
Lab/Imaging
Age
Postmenopause
FH of osteoporosis
Treatment
Low dose Ca/VitD
Estrogen
calcitonin
raloxifene (estrogen Ag in bone,
Antag in breast)
Bisphosphonates -Alendronate,
Zoledronic acid (Reclast)
Adjustable RF?
Excessive alcohol
sedentary lifestyle
Complications
Long term bisphosphonate use
causes increased BMD but
increased fractures, increased
osteonecrosis of jaw (rare)
High dose calcium linked to CV
events and vascular calcification
Anti-RANKL Ab - Denosumab
Increased RANKL
Polyostotic
Paget's disease
Monostotic
Genetic predisposition
(chrom 18, overlap w/
familial expansile
3 stage of localized, chaotic(mosaic) bone remodeling:
misshaped legs/head, gait problems, progression over
1. osteoclastic activity
osteolysis, p62
time,warm to touch; moth-eaten deteriorated bone, pitting of 2. mixed osteoclastic-osteoblastic activity, where osteoblasts try mutation- nl degrades
pagetic bone; usually involves spine/ skull, most painful in
to compensate with deposition of disorganized,
RANKL signaling;
pelvis/long bones
hypervascularized lamellar bone
Juvenile Paget's 3. exhaustive (burnout) stage (dense pagetic bone as
mutated OPG)
hearing loss, platybasia (softening at skull base--> headache
hypercellularity of bone diminishes)
w/ valsalva), Pagetic steal syndrome (shunt blood to ext
Problem with osteclasts
carotid, stroke-like sx), osteoporosis circumscripta (bone loss All results in deformity, fracture, metabolic derangement
(inc #, size, nuclei, fx,
around skull), leontiasis ossea (rare, enlarged facial/jaw bones),
sensitivity to vitD); nl
DIsorganized
communication
btwn
osteoclasts
and
osteoblasts
osteoblasts
high output heart failure
(coupled chaotic activity)
possible involvement of
slow viral inf
Dense, brittle bone that fractures, bleeding/infections,
hypersplenism, hemolytic anemia
Count osteoclasts - RANKL mutation (low OC #) v. TC1RG1/
ClCN7 (nl OC #)
Osteopetrosis
Autosomal dominant (Albers-Schonberg)
(ARO)
Pycnodysostosis
N/A
Facial dysmorphism? Missing jaw look, large forehead,
underdeveloped nose, asymmetry
renal tubular acidosis, cerebral calcifications, hypotonia,
weakness, mental subnl
Phenotype less severe w/ age
Carbonic Anhydrase II
deficiency
Progressive Diaphyseal
disease
Camurati-Engelmann
Endosteal hyperostosis
Sclerosteosis
Van Buchem
Worth type
Fibrodysplasia ossificans
N/A
progressive (FOP)
Osteomyelitis
Acute
Chronic
Hematogenous
Age
200,000 cases in U.S.
(~3% prev)
5-20% w/ symptoms
M>F
Unregulated TGF-B
causes overstimulation
Variable age, severity,
of osteoblasts and
course
excessive bone
formation
hypercalcemia (immobilization)
Deactivating mutation in
SOST (Wnt inhibitor)
Nl OC
Possible inc alk phosphatase
Possible optic atrophy, facial
nerve palsy, deafness
Deactivating mutation in
SOST (Wnt inhibitor)
Mutation in LRP5,
prevents binding of
DKK1 (Wnt inhibitor)
Excessive BMP
stimulation -->
increased osteoblast
formation
NO BIOPSY!!!!
Require wheelchair by 3rd
decade
More common in kids
Ortho surgeries
Nl OC
Possible inc alk phosphatase
MOST common in kids IVDU - novel organisms in unique Adults - elevated ESR/CRP
sites
XR? Takes a while to show signs, but periosteal
elevation, areas of demineralization, loss of sharp
bony margins, moth eaten appearance, possible soft
tissue swelling
CT? sensitive
Bone scan? Early dz (lots FPs)
MRI? GOLD Standard! detects early changes & abnl
soft tissu; adjacent vertebrae involvement
IVDU- S. aureus, P.
aeruginosa, Serratia
Contiguous
Fractures
Immunocomp - fungi
IV DRUG USERS? Sternoclavicular joint, SI joint, pubic
bones
Autosomal recessive
Possible polymicrobial
(see diabetic foot ulcer
bacteria)
Mixed gram+/-,
anaerobes
MOST common in
adults
Revascularization
Disease
Septic arthritis
Clinical Variants
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
Acute bacterial
swollen, hot, monoarticular arthritis w/ passive motion; less Generally hematogeous spread of bacteria or possible
uncommon - fever/chills
iatrogenic spread (joint injections for RA/OA)
Chronic septic arthritis
Bactermic form:
Dermatitis that coincides w/ pustules/papules that are
sometimes hemorrhagic; centrifugic distribution, fever,
tenosynovitis, polyarthalgia/arthritis
S. aureus
Streptococci
GN rods
Mycobacteria (Tb)
Lyme disease
Fungi
Rubella, mumps,
parvovirus
Neisseria gonorrhoeae
F>M
declining incidence
Localized form:
purulent arthritis (1,2 joints)
Acute onset joint pain, effusion, erythema, warmth, fever
Lab/Imaging
Treatment
IV ceftriaxone
Joint replacement
Complications
Late (>2y)
S. aureus,
Streptococci, Gram rods, enterococci,
anaerobes, fungi (rare)
Rising incidence w/
increased joint
replacement surgeries
Risk factors
Recent trauma (animal/ human
bites)
Immunocompromised
RA/gout/sickle cell
IVDU
1/5000 individuals;
classical form is most
common
Beighton score
Autosomal dominant
baseline echocardiogram for kids <10 y.o.
Tx manifesting sx
Low-resistance exercise to increase
muscle tone
Vit. C & D, Ca supplem
Avoid high impact force
Vascular
Dermatosparaxis
Severe skin fragility, sagging/redundant skin, large hernias Deficiency in type I procollagen N-peptidase
Autosomal recessive
inheritance
Kyphoscoliosis
Decreased lysyl
hydroxylase
Autosomal recessive
inheritance
N/A
Celiprolol (cardioprotective)
Marfan Syndrome
Stickler Syndrome
3 collagen genes:
COL2A1, COL11A1,
COL11A2
Type I
Osteogenesis Imperfecta Type II
(OI)
Type III
Type IV
Type II - perinatal lethal form, multiple fx in utero, dark blue Group of heritable conditions characterized by bone fragility
and low bone mass; usually caused by mutations that silence
sclerae
one allele, resulting in decreased amount of normal type I
Type III- may have in utero fx or fx @ birth, thin ribs, popcorn collagen synthesized
epiphyses, short stature, hearing loss common,
dentinogenesis imperfecta (gray/brown teeth that break easily Mutations in COL1A1 and COL1A2; especially, substitution of
and look translucent)
any amino acid for glycine disrupts collagen helical molecule
Type IV- mild-mod, maybe DI, sclerae nl or grey, some hearing
loss
Disease
Clinical Variants
Achondroplasia
N/A
Osteoid Osteoma
Benign
Defining Characteristics
Short stature w/ disproportionately short arms/legs,
macrocephaly, frontal bossing, mid-face hypoplasia, hypotonia
in infancy, delayed developmental milestones
Pathogenesis
Etiologies
Epidemiology
Risk factors
BENIGN
Osteochondroma
Osteosarcoma
Benign
Osteoblastic
Fibroblastic
Chrondroblastic
Telangiectatic
Parosteal
Periosteal
Central low-grade
Secondary
Complications
Compression of spinal cord/
upper airway obstruction
increased risk of death in infancy
>2cm? Osteoblastoma
Benign
Treatment
Chondroma /
Endochondroma
Lab/Imaging
None - benign
If cartilage cap >1cm, start to
worry about development into
chondrosarcoma (RARE)
Chondrosarcoma
Surgery only
Duchenne MD
Becker's MD
Maternal anticipation
Autosomal dominant inheritance associated with trinucleotide
(increases number of
CTG repeats in myotonin-protein kinase gene on C19
CTG rpts)
Clinical exam
McArdle's disease
Ewing sarcoma
Muscular dystrophy
Congenital Myopathy
M=F
35-60 y.o.
Metabolic myopathy
Autosomal dominant
defect in ryanodine
none
M>F
Inflammatory myopathy
Dermatomyositis
Heliotrope rash (periocular edema + violet color) on sunexposed areas; Gottron's papules (red, thickened plaque-like
rashes on extensor surfaces), nailbed hemorrhages,
violaceous erythema (shawl sign), dilated capillary loops of
proximal nail folds, cutaneous calcinosis (ROCK hard)
1/100,000
F>M
Kids (more calcinosis)
& adults
Polymyositis
Toxic Myopathy
Myopathies from
systemic dz
Polymyalgia Rheumatica
N/A
(PR)
Dx critieria:
Persistent proximal pain (>1m) involving (neck, shoulders,
pelvic girdle- 2), >1h morning stiffness, abrupt onset of illness
(<2wks), age>50, Rapid response to low dose prednisone,
elevated ESR, absence of other disorders (flu, hypothyroidism)
Genetic component
(HLA-DR)
Pain perception
thresholds decreased
(abnl neurochem)
Fibromyalgia (FM)
F>M
Extremely unlikely in
pts <50y.o.
Peak onset
30-55y.o.
Clinical dx
Prev? 4% of population
F>>M (10:1)
Elevated ESR/CRP
Thrombocytosis (hi platelets)
Nl CPK
Anemia of chronic dz
Negative ANA, RF
Corticosteroids
No anemia
Nl CPK, aldolase
Nl ESR/CRP
Nl thyroid studies
Negative ANA, RF
Pt education
Anti-inflammatory/ analgesic meds
(not better than placebo)
AVOID NARCOTICS
tricyclics (muscle relaxant, antidep)
Serotonin reuptake inh
Lyrica (decrease perception of pain)
FITNESS TRAINING! (low impact
aerobics and muscle strength)
Disease
Clinical Variants
Defining Characteristics
Rheumatoid Arthritis
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Clinical exam? Prodrome malaise/fatigue, stiffness that
improves w/ activity, non-reducable deformities (swanneck, boutonniere, trigger finger, MCP subluxation,
ulnar dev, hammer toes)
Prev? 1% of pop
F>M (2.5:1)
Peak onset?
35-50y.o.
RA in men <45
unusual!
Elevated ESR/CRP
Anemia
Thrombocytosis
+RF (80-85%, worse dz)
Anti-CCP (90-95%SP)
>2000 WBCs in joint fluid
XR? periarticular osteopenia, uniform narrowing
around joint, marginal erosions, C1-C2 subluxation,
ulnar dev
Treatment
NSAIDS
DMARDS:
-Immunosuppressants (MTX,
leflunomide, azathioprine)
- secondary agents
(hydroxychloroquine,
glucocorticoids)
-TNFa antagonists (Etanercept,
Infliximab, Adalimumab,
Golimumab)
-IL-1R Antagonists (Anakinra)
-T cell costimulatory blockers
(Abatacept)
-Combo tx
Osteoarthritis
Older individuals
Trauma
Infection
Crystsal dz
Neuropathy
Nl ESR/CRP/platelets
Nl hematocrit
<2000 WBC in joint fluid
XR? Osteophytes (bone spurs), asymmetric joint
space narrowing, NO PERIARTICULAR
OSTEOPENIA!
Acetaminophen
NSAIDs
Eventual joint replacement surgery
Complications
Extra-articular manifestations?
Heart - pericarditis,
atherosclerosis
Lung - pleural effusion, interstitial
lung dz
Skin - nodules, vasculitis
Neuro- carpal tunnel (Bilateral),
cervical myelopathy, entrapment
neuropathy
Heme- anemic, thrombocytosis,
FELTY'S TRIAD (RA,
leukopenia, splenomegaly)
Bone- osteopenia
Eye- inflammation
Kidney - rare
Risk for neuro damage w/ C1-C2
subluxation
Disease
Clinical Variants
Episodic monoarticular
Gout
Polyarticular
Tophaceous gout
Defining Characteristics
Systemic Lupus
Erythematosus (SLE)
Pathogenesis
Etiologies
Epidemiology
Prev? Males
5-28/1000; females 16/1000
Hyperuricemia, tophi
Risk factors
>6.7mg/dL solubility of
monosodium urate crystals
Paget's, Psoriasis
certain cancers
excessive alcohol intake
Co-infection of joint
Lab/Imaging
Complications
Treatment
Others?
Antimalarials (hydroxychloroquine)
Accelerated atherosclerosis
Prev? 1/2000
Chronic fatigue!
Raynaud's
periungal erythema
Cutaneous vasculitis (palpable purpura)
Seen w/I first few months of life
Neonatal lupus
Mom w/ lupus
Drug-induced lupus
Thrombocytopenia
Anti-rho antibodies
Positive ANA
Scleroderma (SS)
(General)
F>M
Cell mediated and
humoral immunity
Widemouth diverticuli
Watermelon stomach
(telangiectases in stomach)
pericarditis, arrythmias
Diffuse
Crackles w/ inhalation
Onset of skin changes w/I 1 year of Raynauds
Truncal & acral skin involvement
Anti-Scl-70 Ab
Anti-centromere Abs
Calcinosis, Raynaud's (long duration), Esophageal
dysmotility, Sclerodactyly, Telangiectases
Localized cutaneous SS
GERD? PPIs
MSK? NSAIDs, PT, low dose
steroids (but watch renal!)
Raynaud's? Smoking cessation
PAH? Oxygen, calcium channel
blockers, prostacyclin derivatives
Anti-RNP Abs
Mixed connective tissue disease (MCTD) - SLE, SS,
polymyositis, & positive anti-RNP
NSAIDs & glucocortocoids for pain
& inflammation
Chronic inflammation causes bone formation and erosion -->
fusion of joints (ossification of annulus fibrosus in vertebrae)
Axial arthritis (bilateral sacroilitis, spondylitis), arthritis of
girdle joints, acute anterior uveitis (inflamed iris), extraskeltal
manifestations (aortic insufficiency, conduction abnl, decreased
chest wall expansion, spinal cord compression, cauda equina
syndrome)
Ankylosing Spondylitis
Molecular mimicry impt- genetically susceptible person w/ HLAB27 is exposed to unkwn antigen that causes an immune
response that exhibits cross-reactivity w/ self tissues, causing
clinical expression of spondyloarthropathy (joint dz of
vertebral column)
M>F
Age onset? 20s
HLA-B27
HLA-B27
Psoriatic Arthritis
Disease
Clinical Variants
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Treatment
Reiter's / Reactive
arthritis
Inflammatory bowel
associated arthritis
M=F
young adults
HLA-B27
(See AS path)
Complications
Screening / Education
Protective clothing, daily use of
sunscreen, no sunbathing/ tanning
bed, vit D supplementation for
immunocomp; screening for field
disease changes - CAPABLE OF
DEVELOPING INTO SCC
Screening / Education
Screening / Education
Screening / Education
Adjustment of risk factors (excessive
alcohol, sedentary lifestyle)
Prophylactic bisphosphonate
treatment prior to surgery!!!
Screening / Education
Stay active!!
Screening / Education
Screening / Education
Screening / Education
Screening / Education
Disease
Clinical Variants
Defining
Characteristics
tachypnea, hypoxia
hydrostatic pulm
edema: fluid
accumulates in low P, hi
comp areas (perihilar
interstitium, alv
interstitium, alveolus);
bronchospasm seen
more commonly, sx of
congestive heart failure,
cardiac dysfxn, fluid
overload, NO PREEXISTING ACUTE
TRAUMA
Pathogenesis
Etiologies
Thickened
membranes =
diffusion; LV heart
failure (MI, chronic
CHF), renal failure,
Hydrostatic edema (most
common): Increased hydrostatic IV fluids
pressure (due to LV heart failure)
injury to capillaries
= Pulm edema --> backup of
(free radicals,
fluid into pulm vasculature -->
chemicals)
blood vessel distention by Jreceptors --> tachypnea
Starlings law
reasons for edema:
Permeability edema (more
gradient btwn
severe): direct injury to
capillary &
capillaries (ALI, ARDS) capillary leakage into interstitial interstitial hydrost
permeability pulm
pressure;
edema: diffuse leakage of space overflows the alveolus
gradient btwn
with proteinaceous fluid (can
fluid (patchy, bilateral
interstitial fluid &
be caused by pneumonia,
accumulation),
aspiration, inhalation, sepsis,
oncotic press,
gravitational gradient
(more edema at base); trauma, pancreatitis, transfusion) leakiness of
capillaries;
protein leakage; acute
lymphatic flow
inf, no CHF
Pulmonary Edema
Obstructive lung
disease
Emphysema, chronic
bronchitis, asthma
Restrictive lung
disease
Parenchymal lung
reduced lung volumes
disease (interstitial lung
dz); nonparenchymal
(chest wall disorder;
muscular weakness; less
shifted towards RV)
Risk factors
Lab/Imaging
PFTs: FEV1/FVC<70,
FVC, FEV,
concavity on exp limb
of flow-vol, volumes
(due to air trapping),
spirogram shows slow
initial upstroke & late
vol changes; DLCO
PFTs: nl or >70
FEV1/FVC; FVC,
FEV, spirogram
shows no late vol
changes/ rapid
upstroke, flow-volume
has VC, volumes
shift towards RV
neuromuscular dz:
somewhat higher RV,
low IC
PFTs: FVC nl/, FEV1
nl, FEV1/FVC nl, TLC
nl/, RV nl, DLCO
pulmonary vascular
disorder
Central Airway
Obstruction
Epidemiology
Treatment
Resolution?
Hydrostatic: intact
alv epithelium pumps
fluid out w/ Na/K
ATPase;
tx underlying cause;
Permeability: alv
epithelium injured so
takes longer to
resolve; tx primary
injury cause, manage
fluid balance,
supportive care
Complications
increased hospital
stay (leading to other
comorbidities) and
high mortality for
permeability edema
Disease
Clinical Variants
Intra-thoracic obstruction
Defining
Characteristics
Plateau on expiration
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Treatment
Complications
Disease
Clinical Variants
Fixed lesion
COPD
Emphysema
(blow a balloon up and
release it? No air flows
out bc loss of elastic
recoil)
Defining
Characteristics
Plateau on inspiration &
expiration
Pathogenesis
A1AT deficiency
panacinar emphysema
Chronic bronchitis
typically presented as
overweight, cyanotic,
edematous, productive
cough, dyspnea at rest
Etiologies
Epidemiology
Risk factors
large tumor
Subglottic
stenosis, goiter,
tracheal stricture
hyper capillary surface #4 mortality in
responsiveness,
area = diffusion; world & USA
lung growth,
cell mediators?
F>M
exposure to
Epithelial cells,
tobacco smoke/
macrophages,
middle aged
occupational
CD8+ (TH1),
(~50y.o.)
dusts & chems/
neutrophils
infections/ SES SMOKING (USA) develops in about nutrition
15% of smokers
Air pollution
(global)
decreased elastic
recoil
Lab/Imaging
Complications
alpha1antitrypsin
deficiency, FH
of A1AT def,
smoke, dust,
kerosine, PiSZ
smokers
Treatment
management?
Prevent dz
progression, relieve
sx, improve ex
tolerance, improve
health status,
prevent/ treat
exacerbations,
reduce mortality
drugs generally
less effective
Short acting
bronchodilators (Bagonists - albuterol,
levalbuterol,
metaproterenol,
pirbuterol;
anticholinergics like
ipatropium)
long acting
bronchodilators (Bagonists - salmeterol,
CXR: radiolucency in formoterol)
base of lung
(vs. diffuse
sometimes
emphysema in other
phosphodiesterase
variants)
inhibitors
(theophyline,
roflumilast)
PFT: see obstructive
dz
responds poorly to
meds
anti-inflammatory
inhaled steroids
(fluticasone,
budesonide,
mometasone)
home O2 if
hypoxemic
(prevents cor
pulmonale)
hoarseness =
common side effect of
steroids
Could require oxygen,
pulmonary
rehabilitation, lung
volume reduction
surgery, and/or lung
transplantation
cor pulmonale
Disease
Asthma
Clinical Variants
Defining
Characteristics
Pathogenesis
hygiene hypothesis: early
exposure to infectious agents=
TH1 response= suppression of
TH2 activation= allergy
/asthma frequency; people less
likely to be exposed to these
infections today= TH2 cells
mediate onset of asthma
Airway remodeling occurs in
pts w/ uncontrolled chronic
asthma (older pts)
morphological changes in
asthma (hyperplastic mucus
gland/goblet cells, infiltration of
inflammatory cells, thick BM,
edema, fibrosis, epithelial
damage) = Smooth muscle
hypertrophy = reversible
bronchoconstriction, hyperresponsive airflow limitation
Etiologies
inflammatory cell
mediators? Epith
cells, mast cells,
CD4+ (TH2),
eosin, IL4, IgE,
Factors
contributing to
severity?
Environmental
(animal/insect/
mold/outdoor
allergens),
occupational exp,
indoor/ outdoor
pollutants, foods/
preservatives,
certain meds,
infections,
immunotherapy
cold= vagal reflex
= ACh = bronchoconstriction
Epidemiology
Risk factors
Lab/Imaging
Treatment
Complications
Disease
Hypoxia
Clinical Variants
Defining
Characteristics
Pathogenesis
Risk factors
Lab/Imaging
Treatment
Complications
Autosomal
recessive mutation
in gene hydin
failed dynein
motors or central
pair assembly =
cilia paralysis
Flail chest
Lung bullae
Pneumomediastinum
Pneumopericardium
Emphysema
Tracheo-bronchial
tree/ esophagus
rupture from
trauma/ prolonged
vomiting
Fistula btwn 2
structures;
Ventilators
Pneumoperitoneum
Pulmonary nodules
(<3cm); pulmonary
masses (>3cm);
consolidation (think
pneumonia)
CXR: increased
lucency, tension
pnemothorax can push
heart over to opposite
side; acquires soft
tissue (gray-white)
density, thin white
line (Spont)
Lung cavities
Epidemiology
PIO2:FIO2
2,3-DPG
Acute
Chronic
Primary cilia
dyskinesia (PCD),
immotile ciliary
syndrome,
Kartagener
syndrome (KS)
Pneumothorax
(atelectasis - partial
collapse of lung,
collapse of alveoli)
Etiologies
Infection; vasculitis;
tumors
Requires immediate
identification and
treatment, or else
death!
CXR: Air collection
btwn right diaphragm
& liver or peritoneal
cavity
CXR: Abnormal lucencies w/I lung parenchyma
Disease
Clinical Variants
Atelectasis
Defining
Characteristics
Mediastinum pulled
towards affected side
on CXR
Alveolitis
Pathogenesis
Etiologies
Epidemiology
Obstructive Atx of
whole lung?
Cancer, mucus
plug, foreign body
CXR: Complete
Opacification
Hemithorax;
consolidation
Viral, mycoplasma
pneumoniae,
hypersensitivity
rxns
Histology: thickened
septa due to
infiltration of
inflammatory cells;
empty alveolus
space
CXR: Complete
Opacification
Hemithorax; blunted
costophrenic angle,
meniscus sign (upside
down U), loss of nl
structures at lung base
pathological accumulation of
Mediastinum pushed
away from affected side fluid in pleural space, which
becomes a vulnerable place due
to large size & surface area,
Common sx? Dyspnea
(increased inefficiency of negative pressure pulls fluid in,
and relatively leaky borders from
resp muscles, NOT
gap jx btwn mesothelial cells
hypoxemia), cough,
Exudative (occur when
pleuritic chest pain
Starling's forces: Pcap (CHF,
local dz stimulates pleural
fluid formation; inc cap
Decreased breath sounds vol overload), cap oncotic
over area of pleural
perm -pneumonia;
pressure (cirrhosis, nephrotic
effusion (Base of lung),
obstruct of lymph
synd), Lymphatic clearance
dullness to percussion
drainage - cancer);
(lung cancer, lymphoma)
capillary barrier disrupted
so high protein content
Increased permeability pleural dz, malignancy, infxn
Transudative (occur
when systemic imbalance
of Starling's forces - inc
hydrostatic press, dec
serum onc press) - low
protein content
malignancy, PNA/
Infxn, PE, post
surgical
transudative pleural
effusion
Treatment
Complications
TB (global cause)
thoracentesis!! (dx &
tx effects)
Light's criteria >1
exudative
Cell types:
Neutrophils? inf/symp
causes; Lymphocytes?
cancer, TB; RBCs:
hemorrhagic
(malignancy, TB, PE,
trauma), hemothorax
Hepatic hydrothorax
Lab/Imaging
Risk factors
diuretics
do not attempt
pleurodesis!!
Beta blocker to
decrease portal
pressure
ascites
RUQ
transplant
Parapneumonic
Effusions (PPE)
Exudative pleural
effusion
no bacteria or pus in
pleural fluid
40% of bacterial
pneumonia
develop PPE
Thickened visceral
membrane (makes
lung expansion
difficult)
Antiobiotics for
exudative stage;
chest tube drainage
for fibrinopurulent
stage; decortication
for organized stage
complicated bloody
surgical procedure
Disease
Clinical Variants
Empyema
Malignant Pleural
effusion
Defining
Characteristics
Pathogenesis
Etiologies
Epidemiology
Exudative pleural
effusion
Risk factors
Lab/Imaging
Treatment
Complications
hematogenous metastases to
parietal pleura
Thoracentesis: gross
pus or positive gram
stain, pleural fluid
cultures
(always
low
pleural fluid
cytology
pleurodesis
positive in 60-80%
possible pleural bx
Chylothorax
Exudative pleural
effusion
trauma or
CANCER!
mPAP >= 25
PWP <= 15
No significant obstructive/
restrictive lung dz, left
heart dz, or
thromboembolic dz
Proliferation, vasoconstriction,
thrombosis, remodeling
idiopathic (see
below), heritable
(BMPR2, Alk1,
d/os like CTD (Scleroderma),
endoglin), drug/
HIV(s vascular mediators to
toxin induced
favor vasoconstriction),
(amphetamines,
cocaine, St. John's
portopulmonary dz ( portal
vein press, backflows to heart), wort), other
disorders,
congenital heart dz (atrialpersistent
septal defect shunts systemic
pulmonary HTN of
blood into pulm circ),
newborns
schistosomiasis (eggs from
(foramen ovale
organism occlude pulm artery,
remodeling), chronic hemolytic doesn't close)
anemia ( NO =
vasoconstriction)
Endothelin pathway: in PAH=
vasoconstriction & smooth
muscle hypertrophy
Nitric oxide pathway: in PAH,
nl causes vasodilation, broken
down by phosphodiesterase
Disease
Clinical Variants
Idiopathic Pulmonary
Arterial Hypertension
Defining
Characteristics
slowly progressive
DOE, syncope w/
exertion, chest pain,
palpitations
loud pulmonic valve
closure (P2), tricuspid
regurgitation murmur
on LSB, right sided fourth
heart sound (increased
press through tricuspid
valve), right ventricular
heave, peripheral
edema, ascites, JVD
Valvular diseases,
systemic dysfunction,
diastolic dysfunction
Etiologies
Significant overgrowth in
Unknown?
endothelial layer of pulmonary
arterioles (vascular
remodeling) = obstruction of
blood flow (plexiform lesions) =
pulmonary vascular resistance
(PVR is too high!!), problems
w/ perfusion
Epidemiology
Risk factors
20-30 y.o.
Lab/Imaging
histology? Intimal/
smooth muscle/
adventitia
hypertrophy &
formation of
plexiform lesions
F>M (2:1)
Treatment
see PAH
see PAH
mPAP >= 25
PWP > 15
no meds approved
for this population
severely decreased
DLCO
see PAH
uncommon, subacute
manifestation of pulmonary
embolic disease that evolves via
proximal pulmonary artery
obstruction from failed clot
resolution --> remodeling to
increase pressure backflow to
RV
Pulmonary arterial
hypertension from
Left heart disease
Pathogenesis
(WHO Group 2)
Pulmonary arterial
hypertension from
lung disease/
hypoxia
(WHO Group 3)
Chronic
Thromboembolic
Pulmonary HTN
(CTEPH)
(WHO Group 4)
incidence of
CTEPH happens
w/I 2y of acute
VTE
younger age,
larger PE,
idiopathic VTE,
hx of previous
PE
Complications
High mortality without
treatment (median
survival 2.8 yrs) - cor
pulmonale
Disease
Clinical Variants
Defining
Characteristics
Pulmonary arterial
hypertension w/
unclear or
multifactoral causes
Pathogenesis
Risk factors
Lab/Imaging
Treatment
Complications
Chronic
myeloproliferative
dz, splenectomy,
sarcoidosis, LAM,
pulmonary
langerhans cell
histiocytosis,
glycogen storage
diseases, hyper/
hypothyroidism,
end stage renal dz
see PAH
Diffusion-perfusion impairment =
overdistention of capillary =
RBCs escape w.o oxygen
traveling to other side (bc
capillary is too wide) = R-L shunt
hypoxemia (PVR is too low!!)
Liver disease
(causes
vasodilation &
capillary overdistention)
Hepatopulmonary
syndrome
Secondary to liver
disease
Hyperventilation /
Hypocapnia
decreased effective
minute ventilation =
PaCO2 > 45
(hypercapnia)
Epidemiology
(WHO Group 5)
Hypoventilation /
Hypercapnia
Etiologies
Physiologic
causes? Hypoxia,
acidosis, irritants
(P.E., inhalants),
CHF (J-receptors)
Non-physiologic
causes? Pain,
anxiety,
psychogenic
NOT related to RR
treat underlying
disease, brown
Diagnostics?
paper bag
Pregnancy test, ABG (increases blood
(pH, pO2, HCO3-,
CO2 because closed
pCO2), kussmaul
system),
breathing (slow deep reassurance,
breathing classic in
sedation?
acidosis)
sepsis, PE,
pregnancy
Brain: congenital
central
hypoventilation
(hirchsprung's dz),
chronic hypercapnia? pH w/
hypothyroid,
time, kidney compensates w/
central alveolar
HCO3; RBCs (polycythemia), sedatives/narcotics
hypoventilation? No
baroreceptor sensitivity (high / benzos,
anesthesia,
dypsnea, hypoxemia
PCO2 causes less minute
secondary to hypercapnia ventilation than expected); rely Ondine's curse;
on secondary drive to breath muscle & PNS:
ALS, MG, MD,
neuromuscular
(hypoxia)
kyphoscoliosis,
hypoventilation?
obesity
Orthopnea (loss of
2 consequences? -HCO3,
hypoventilation
diaphragm fx), cor
cerebral vasodilation
syndrome; lung:
pulmonale (terminal
(headaches), sleep arousal
COPD, Asthma,
event)
(sleep disturbance,
bronchiectasis,
somnolence), Hb desaturation/
pulm fibrosis
erythropoiesis (cyanosis,
polycythemia), pulm
common cause for
vasoconstriction (pulm HTN, cor
resp acidosis?
pulmonale)
DRUGS, stroke
Central cause? Nl
PFT, nl muscle fx,
impaired hypoxic drive
(problems with
unconscious breathing
only)
Neuromuscular
cause? FEV1,
FVC, TLC, RV
(restrictive pattern),
weak muscle fx (low
pressure, forces,
MVV), rapid shallow
Lung dz cause?
obst/rest pattern on
PFT, nl muscle
strength but low
MVV/endurance;
hypoxic drive alone w/
chronic hypercapnia
Respiratory
acidosis? Correct w/
drug antagonist,
intubate
Central alveolar
hypoventilation?
Respiratory
stimulants,
diaphragmatic
pacing, nocturnal
ventilation
neuromuscular?
NO stimulants, tx
underlying condition,
nocturnal ventilation
pulm? Treat
underlying dz,
careful O2
supplementation,
nocturnal ventilation
do not give
supplemental
oxygen to patients
with chronic
hypercapnia (only
drive to breathe is
hypoxia!!)
Disease
Hypoxemia
Clinical Variants
Defining
Characteristics
Pathogenesis
FIO2;
hypoventilation;
diffusion
impairment; VQ
mismatch; shunt (RL), altitude induced
hypoxemia
General
hypoventilation induced
hypoxemia
Etiologies
hi ventilation, low
perfusion (PE)
anatomic shunt
(intracardiac
shunts, pulmonary
AV malformations,
hepatopulmonary
syndrome)
low ventilation, hi
perfusion
(pneumonia, PECHF, ALI/ARDS,
atelectasis,
pulmonary fibrosis,
COPD)
physiologic shunt
(atelectasis,
pneumonia,
ALI/ARDS)
Diffusion limitation
hypoxemia
interstitial lung
disease,
pulmonary
fibrosis
Epidemiology
Risk factors
Lab/Imaging
Treatment
patients respond to
increased FiO2
Complications
Disease
Acute respiratory
failure (ARF)
Clinical Variants
Defining
Characteristics
Pulmonary
hypertension
Pulmonary
embolism
Pathogenesis
Etiologies
nl CXR? Possible
causes = CNS
event (stroke, drug
OD, head injury),
neuromusc dz,
airway obst
(asthma, COPD),
PE
abnl CXR?
Possible causes =
ALI/ARDS,
aspiration,
pneumonia,
hydrostatic pulm
edema, obst lung
dz (nl/abnl CXR),
PE (nl/abnl CXR),
pneumothorax
Epidemiology
Risk factors
Lab/Imaging
at-risk dx?
Direct lung
injury (aspiration
of GI contents,
pulmonary
contusion,
pneumonia/
sepsis); indirect
lung injury (nonpulm sepsis,
abdominal
trauma, multiple
fx, hypertransfusion)
300<PaO2/FiO2<200
CXR: bilateral
infiltrates
ABG: worsening CO2
and O2 levels despite
increased oxygenation
ILD
DLCO
gross: thickened
pulmonary arteries
(white macaroni)
DLCO
600,000 PE, 1
same as those
million silent PE; for DVT
3rd most common
CV disease in US
Treatment
manage underlying
cause
Complications
mortality ~30-40%,
long recovery time
provide supportive
care
restore oxygenation
to better levels
(PaO2 of 55-60, O2
sat 88-90%)
intubation & low tidal
volume mech
ventilation if
necessary
anti-coagulation!!
(short term - LMWH
Well's criteria: >6pts = heparin, unfract
high risk (78%), 2-6
heparin; long-term pts= mod risk (28%), coumadin)
<2pts = low risk
(3.4%); modified (>4 Thrombolytics if
pts = PE likely!!)
low BP (shock
state)
Christopher study:
low modified Wells =
D-dimer (nl - done;
abnl - CT scan), CT
scan (nl - done,
positive -tx); hi
modified Wells = CT
scan (nl - done;
positive- tx)
Alternatives? VQ
scan, abnl pulm
angiography
increased mortality if
PE+shock
65% of people die w/I
1st hr of dx
Thrombolytics
contraind in pts >80,
major surg w/I 7d,
major trauma w/I 10d,
TIA/ neurosurgery in
last 6m, GI bleed in
last 3m, uncontrolled
HTN, known bleeding
disorder
Thrombolytics have
increased risk of
intercranial
hemorrhage
Disease
Clinical Variants
Deep Vein
Thrombosis
Defining
Characteristics
swollen leg, tenderness in
leg near deep veins,
unilateral swelling >3cm,
unilateral pitting edema
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
2 million cases,
1/1000 per yr;
M>F, blacks more
affected
Trauma, spinal
cord injury, ortho
surgery, Gyn
surgery, critical
care
Complications
AVOID giving anticoagulation
prophylaxis to spinal
surgery patients
Pulmonary fibrosis
Treatment
DLCO
histology: blue-pink
color as collagen
deposits develop
fibrosis; thick, stiff
looking alveolar
spaces; temporal
heterogeneity
(normal septum next
to disease septum)
gross: honeycombing
(bumpy cobblestone
pleura; tethering of
fibrin); traction
bronchiectasis (dilated
bronchi)
Obesity
hypoventilation
syndrome
"Pickwinian's syndrome"
Acute
Laryngotracheitis
"Croup"
DLCO
morbid obesity,
sleepiness &
hypoventilation during
day, hypercapnia,
cyanosis,
hypersomnolence
viral
extrathoracic
obstruction
weight loss
cor pulmonale
difficult to reverse
uncommon in kids
< 6m (maternal
Abs)
most common
cause of upper
airway
obstruction in
kids
Spontaneous
resolution w/
hydration, antipyretics, humidified
air
severe cases? Oral
corticosteroids,
nebulized
epinephrine for
immediate
symptomatic relief
(does nothing for tx
though!!)
inflammation can
extend into lower
airways/bronchi =
laryngeal tracheal
bronchitis
Disease
Clinical Variants
Epiglottitis
Defining
Characteristics
Pathogenesis
Foreign Body
Aspiration
Bronchiolitis
persistent cough or
wheeze,
current/persistent
pneumonia, decreased
breath sounds, delayed
air entry
intrathoracic obstruction
tachypnea (RR>50,60),
chest retractions, cough,
wheezing, prolonged
expiratory phase,
crackles, signficant resp
distress, apnea in young
infants, irritable,
dehydration
inflammation of bronchioles,
intrathoracic obstruction
Etiologies
reduced
vaccination rates
Epidemiology
Risk factors
Treatment
peanuts,
popcorn,
hotwheels, any
small toy
secure airway!!
CXR: hyperinflation
of affected airway
(air trapping) OR
completely nl CXR!!
remove foreign
object
Atelectasis w/
aspiration
RSV, followed by
parainfluenza
CXR: hyperinflation
(air trapping), flat
diaphragm,
peribronchial
thickening,
collapsed lung
(RUL), dense
infiltrates behind
heart (frank
consolidation,
pneumonia)
hospitalize young
child if it looks like
RSV bc high
incidence of sleep
apnea --> SIDS
possible O2
supplementation
fluids (hypertonic
saline), hold feeds,
humidified O2,
infection control
no routine
bronchodilators,
antivirals,
corticosteroids, or
antibiotics
Non-atopic wheeze
Complications
MEDICAL
EMERGENCY!! High
Do NOT inspect
risk of death (if
edema progresses
airway or place IV
thumb sign on lateral
enough to position
XR (but really would
intubation by most epiglottis over the
never get bc could
experienced person airway)
worsen obstruction) Hib manifestations
swollen, enlarged
IV fluids, labs,
elsewhere (meningitis,
epiglottis
antibiotics (3rd gen
otitis, pnuemonia,
cephalosporin),
cellulitis)
airway/blood
cultures, rifampin
prophylaxis for
close contacts, NO
nebulized
epinephrine
foreign objects
Lab/Imaging
NOT FH of
asthma
reduced lung fx
before
respiratory
event
(prematurity, day
care, prenatal
maternal
smoking, post
natal smoking
exposure)
preschool age
kids
Many develop
recurrent wheezing
that may be
associated with
persistent
abnormalities in
lung function
Disease
Clinical Variants
Ig-associated wheeze
(asthma)
Defining
Characteristics
Wheezing before age 6
Pathogenesis
Etiologies
Epidemiology
Bronchiectasis
Interstitial Lung
Disease (ILD) general overview
Lab/Imaging
FH of asthma,
allergy, elevated
IgE @ age1,
early
sensitization to
mold, obese
females,
maternal
prenatal smoking
Cystic fibrosis
Risk factors
connective tissue
diseases,
exposures
contributing to
hypersensitivity
pneumonitis,
drug/smoking
induced, radiation,
toxic inhalation
unk causes? IPF,
other idiopathic
interstitial
pneumonias (COP,
NSIP, LIP, AIP),
sarcoidosis,
eosinophilic
pneumonia, rare
(LAM, PLCH, PAP)
Treatment
Complications
inhaled
corticosteroids
Sweat test
(pilocarpine
iontophoresis) - nl
~40; CF ~90-100
Spirometry
CFTR modulators
(Ivacaftor, VX-809,
PTC124)
aw clearance
Gentoyping (specific, (dornase alfa,
not sensitive)
hypertonic saline,
bronchodilators, PT)
Newborn screening Aerosilized abs for
(measures IRT
exacerbations
combined w/
Anti-inflammatories
genotyping; confirmed (prednisone,
by sweat test)
macrolidesPsuedomonas)
Late stage PE findings Nutrition: caloric
(respiratory failure,
foods, appetite
FTT, malnutrition,
stimul, tx constipat,
steathorrhea)
pancreatic enzymes
& PPIs to minimize
CT: air trapping,
malabsorp
bronchiectasis
yearly CT scans @
age 1
lung transplant
CT: cysts
Gross pathology:
irreversible damage
PFTs: restrictive
pattern (low TLC0,
decreased DLCO
(thickened alv
membrane)
CXR: bilateral reticular
infitrates, basilar distn,
small lung vol
CT: diffuse ground
glass infiltrate, mixed
pattern (consolidation
+ GG), reticular
peripheral infiltrates;
honeycombing
(advanced fibrosis),
traction bronchiectasis
ABG: hypoxemia
Life expectancy
~40y.o. but improving
w. earlier dx and
better tx
Increased tendency
for infections (never
really eradicated, just
controlled) - Staph,
H.flu, Pseudomonas
Pulmonary
exacerbations
usually require
hospitalization
(better adherence w/
aw clearance
therapies)
prednisone leads to
decreased loss of lung
fx but toxic w/ chronic
use
Disease
Clinical Variants
Defining
Characteristics
Chronic, progressive,
fibrosing, interstitial
Pathogenesis
"repeated cycles" of epithelial
activation or injury by some
unknown agent
Etiologies
Unknown?
limited to lungs!
Dyspnea (insidious but
progressively worsening);
non productive cough
(difficult to control),
clubbing, decreased
breath sounds, bilateral
crackles
Epidemiology
Risk factors
high mortality!!
Age (>50)
familial pulm
Older adults, M>F fibrosis
128,000 pts (US) smoking
40,000 new
GERD
cases/yr
exp to metal
25-30/100,000
dust, wood dust,
solvents
Desquamative interstitial
pneumonia (DIP)
Acute interstitial
pneumonia (AIP)
Respiratory bronchiolitis
interstitial lung disease
Cryptogenic organizing
pneumonia (COP)
"Bronchiolitis obliterans
organizing pneumonia"
BOOP
localized or diffuse
consequence of infection or
inhalational injury
No FDA approved
med tx
Complications
About 50% survival
after 2 years dx; 1520% 5 yr survival
steroids
HARMFUL!!
treat GERD
Enroll in clinical
trials
Evaluate for lung
transplant
O2
supplementation,
pulm rehab,
vaccination for
flu/pneumonia, tx
comorbidities,
maintain BMI
CTDs
DX = exclusion of
other causes, +UIP
pattern on HRCT/bx
CXR: restrictive
findings (smaller lung
volumes), fibrotic
changes
CT: honeycombing,
reticulation, traction
bronchiectasis,
subpleural & basilar
changes
histology: dense
fibrosis + honeycombing, subpleural
involv, temporal
heterogeneity,
fibroblastic foci
Treatment
>90% of cases
involve
smokers!
responsive to
steroids!! (~6m)
Histology? Fibrous
plugging of airway
sometimes present w/
fever (after which Abs
don't help)
Lymphocytic interstitial
pneumonia (LIP)
Non-specific interstitial
pneumonia (NSIP)
Lab/Imaging
better prognosis
than UIP!!
Good results with
steroids
Disease
Clinical Variants
Defining
Characteristics
Drug-induced ILD
Hypersensitivity
Pneumonitis
(extrinsic allergic
alveolitis)
Sarcoidosis
Farmer's lung
Pigeon breeder's lung
Humidifier lung
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
immunologic-mediated,
inflammatory reaction around
small airways in response to
inhaled antigen (organic dust)
NO WHEEZING!
NOT multisystemic (like
early stage: type III mediated
sarcoidosis)
Acute HP (sx w/i 48h, selflate stage: type IV delayedresolving, recurring
type hypersensitivity reaction
episodes more severe,
against antigen
nonspecific sx;
tachypnea, tachycardia,
fine crackles),
does not involve IgE
subacute/ intermittent
HP (gradual sx, low dose
rptd exp, sx resolve w/i
24h of removal from
agent, tachypnea,
crackles) chronic HP
(chronic exp, prod cough,
DOE, weight loss,
tachypnea, crackles,
irreversible after removal
of agent)
asymptomatic
Non-infectious, nonnecrotizing granuloma
Systemic disease, nonspecific & variable
presentation (lungs, skin)
Heerfordt's syndrome:
parotid swelling, uveitis,
Bell's Palsy, fever
Lofgren's triad: arthritis,
erythema nodosum,
hilar adenopathy - good
prognosis
The sicker a person
appears on presentation,
the better the prognosis!
Treatment
Complications
remove responsible
drug!
Non-smokers
Microbial agents
(bacteria, fungi,
amoeba, atypical
mycobacteria),
Animal proteins
(bird antigens), low
& high MW
chemicals
Histology:
bronchiocentric
lymphoplastic
infiltration, poorly
formed nonnecrotizing
granulomas,
mutlinucleated giant
cells around
bronchioles,
must stop
exposure!! Only
then will steroids be
effective
may progress to
chronic HP w/ end
stage fibrosis &
honeycombing
spontaneous
resolution but
management differs
based on location of
involvement
Unknown?
3x higher
incidence/ severity
in African
Americans
Some genetic
component (HLA
II on
chromosome 6
short arm)
histology: nodular
aggregate of mo w/o
necrotizing center;
periphery of
lymphocytes (wreath
Scandavian
arrangement of
countries
decreased risk nuclei),
in HIV pts!
multinucleated giant
young person's
cells
disease (age<50) Worse
CXR:
prognosis? Pts lymphadenopathy in
F>M
>40y.o, A.A.,
young person;
hypercalcemia, interstitial fibrosis;
nephrosclerosis, determines staging (0extrapulm dz
no pulm inv, 4irreversible fibrosis),
nodular sarcoids
PFT: any pattern but
classic (nl ratio, low
DLCO, restriction or
mixed pattern)
BAL: increased
lymphocytes, >3:1
ratio of CD4:CD8
glucocorticoids if
worsening pulm sx,
worse lung fx,
changes in CXR; 612m
lung transplant if
stage 4
Disease
Pneumoconsioses
(occupational lung
dz)
Clinical Variants
Asbestosis
Coal workers
pneumoconiosis
Silicosis
Berylliosis
Anthracosis
Community acquired
pneumonia (CAP) Typical pneumonia
(Pneumococcal
pneumonia)
Defining
Characteristics
Pathogenesis
Etiologies
general
Risk factors
industries that
mine, fabricate,
or install
asbestos
(roofing,
insulation,
brakes,
shipyards)
Lab/Imaging
Treatment
Complications
amphibole body a/w
mesothelioma
asbestos exposure
also increases risk for
bronchogenic
carcinoma, benign
pleural plaques
(marker of asbestos
exp), and
mesothelioma
mining and
processing of
ores; stone
cutting/
polishing,
sandblasting,
working w/
abrasives
(pottery)
histology: nodular
type pattern of
fibrosis, silica
particles (needle like
structures) visible
under polarized lens
high incidence of TB
(silicosis =
macrophage wasting
dz so can't fight off
TB)
slight risk for
carcinoma
cor pulmonale
CAP - Atypical
pneumonia
Epidemiology
CXR: lobar
consolidation, pleural
effusions sometimes
Strep pneumo is #1
cause of meningitis in
all age groups
blood cx positive in
20% of patients
Macrolides
(arithromycin),
doxycycline, 3rd
gen
Sputum gram stain:
cephalosporins,
many neutrophils,
sometimes
gram+ cocci in pairs fluoroquinolone
& chains
Mycoplasma
pneumoniae,
Legionella,
Chlamydia
pneumoniae, viral
Disease
Clinical Variants
Legionella
Defining
Characteristics
Pathogenesis
Legionnaires' dz - mild
respiratory dz to severe,
life-threatening
pneumonia; HI fever,
malaise, myalgias,
anorexia, headache,
diarrhea, dry cough,
hyponatremia, pleural
effusion
Etiologies
Epidemiology
Risk factors
Smokers or
people with
damaged
mucociliary
defenses
(COPD)
Lab/Imaging
Gram stain: Gram rod that does not stain
well; requires fuchsin,
silver stains for
visualization
Treatment
Fluoroquinolones
(Levofloxacin,
moxifloxacin,
ciprofloxacin)
Macrolide
(Azithromycin)
Legionella urinary
immuno-deficient antigen - + in 80-90%
Alternatives?
of dz
age> 50
Doxycycline
culture on selective
NO B-LACTAMS!!
media - slow but GS
serology- slow...
Empiric dx due to
difficult cx
Chlamydia pneumoniae
>1/4 of
no seasonal
pneumonias in
variation
school-aged kids
re-infection possible,
asymptomatic carriage,
21 day incubation period;
mild URI sx followed by
prolonged cough,
malaise, no fever really,
nl WBC count
No tx for localized
URIs (without
pneumonia)
cold agglutinins:
antibodies to RBC I Ag B-LACTAMS do not
work (no cell wall!!)
= agglutination of
RBCs at 4 degs C
Pneumonia
Antigen & NA
present? Use
detection kits (future) macrolides
(erthromycin,
azithromycin),
doxycycline (adults),
fluoroquinolones
(adults)
CBC: nl WBC
cell cx not really tried
PCR/NA techniques
(Future)
Complications
histology? interstitial
& alveolar infiltrates
of macrophages
doxycycline,
macrolides,
fluoroquinolones
NO B-lactams!!
immune mediated
systemic
manifestations
(Derm- SJS, CNSencephalitis, Heme hemolytic anemia,
MSK- myalgias,
arthalgias, etc)
Disease
Clinical Variants
Viral pneumonias
Defining
Characteristics
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Treatment
Complications
CMV?
Adenovirus?
Immunocompro Exudates w/ necrosis
mised individuals & hemorr; intranuclr
inclusions w/ blurred
nuclr membrane smudge cell;
CMV? Intra-alveolar
hemorr, edema,
cytomegalic cells
(large cells with
intranuclr &
cytoplasm
inclusions)
HSV? Eosins w/ halo
Measles? multinucl
giant cells w/ intranuclr
inclusions w/ indistinct
halo & cytoplasm
inclusions
Pneumocystis jirovecii
pneumonia (PCP)
Necrotizing
Pneumonia (Lung
Abscess)
focal infiltrates
S. aureus, S.
pyogenes,
Pseudomonas,
POLY-MICROBIAL
immunocompro
mised pts (AIDS,
transplant,
cancer, steroids)
Histology? Looks
bubbly with widened
alveolar septa due to
inflammatory cells;
characteristic cysts
seen w/ silver
staining
Immunocompro
mise; transplant
antimicrobial
Gross: cavitation
(gangrene of lung) w/
surrounding fibrosis,
pus filled
CXR: abscess
formation
Histology: alveolar
space filled w/ PMNs
Aspiration
pneumonia
(severe necrotizing
bronchopneumonia)
debilitated pts
unconscious
pts
repeated
vomiting
Histology:
hemoptysis &
necrosis
High mortality
lung abscess in
those who do
survive
Disease
Tuberculosis
Clinical Variants
Defining
Characteristics
Active TB
Atypical
Mycobacteria
M. avium intracelluaire
complex (MAC)
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Treatment
Complications
1.5 million
deaths/yr; 2nd
leading cause of
death after HIV;
#1 cause of death
in HIV pts
HIV
poor, crowded,
poorly ventilated
settings
malnutrition
RIPE = Rifampin,
isoniazid,
pyrazinamide,
ethambutol for 6-9mdrug susc TB
Lots of undetected TB
cases globally so
need single point of
care test (GeneXpert RT-PCR $$)
start on 4 drugs if
suspicious of TB,
once have
susceptibilities, can
cut back to 2 drugs (4
drugs - 2m, 2 drugs 2m)
MDR-TB (resistance
to at least INH + RIF)
most cases in
Asia & Africa
HIV epidemic is
driving TB
coinfection
immunosuppress
ed (TNF-a
inhibitors,
prednisone)
recent inf w/
latent TB (<2y)
substance abuse
DM, renal failure,
cancer, chemo,
silicosis, fibrotic
changes on CXR
HIV, COPD/other
lung dz
Granulomatous
fungal diseases
(very similar to TB
clinically,
pathologically)
Cryptococcus
granulomatous
inflammatory response
caused by Cryptococcus
neoformans, which is an
encapsulated yeast and
transmited to humans via
inhalation of soil & bird
droppings
dimorphic: mold in
the cold, yeast in the
heat!
GEOGRAPHIC
localization
Histoplasmosis
Inhalation of histoplasma
capsulatum causes isolation of
spores into the lung, after which
only
the fungi intracellularly reside
immunocompromised
individuals progress w/ in macrophages
production of
Histoplasmoma - localized lung
granulomas
lesion that becomes walled off
and calcified
NOT really capsulated! chronic fibrosing
histoplasmosis - aw centered
fibrosing lung dz
Histoplasma pneumonia granulomatous pneumonia
Disseminated histoplasmosisresembles miliary TB
opportunistic
infection!
immune reconstitution
inflammatory
LTBI - tx with INH for syndrome (IRIS) 9 months (or INH/RIF response in TB-HIV
pts started on ARVs
for 1x q 12wks)
Multi-drug therapy
Gross: caseous
necrosis of lung just
like TB
Histology: yeast
(spheres)
surrounded by clear
space (capsule),
which can be stained
with mucicarmin capsules turn pink
XDR-TB (resistance
to INH, RIF, +
fluoroquinolones/
injectable Abs)
DIFFICULT TO
ERADICATE
Disease
Clinical Variants
Coccoidoidomycosis
Defining
Characteristics
multiple budding
various dz presentation,
mostly asymptomatic
(80% of people in
endemic areas infected)
but some people can
have lung lesions, fever,
cough, pleuritic pains,
erythema multiforme
Blastomycosis
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Southwest &
Western US
Histology? Large
organism containg
secondary
component
(spherule w/
endospores) multiple budding
Southeastern &
south central US
Histology? Broad
based budding
CXR: UL involvement
Treatment
Complications
Spontaneous
resolution, or can
persist as a chronic
lesion
pulm sx (productive
cough, chest pain,
abdominal pain, night
sweats, chills, anorexia,
weight loss)
Wegener's
Granulomatosis
Foreign Body
Granulomas
Localized parenchymal
mass
IVDU
Histology?
Multinucleated giant
cells, birefringent
(polarized light will
show talc)
Histology? Lipids in
alveoli cause
formation of
granulomas
if untreated, mortality
corticosteroids +
cyclo-phosphamide w/I 1 year
poor prognosis related
to # sites involved,
renal involvement,
age, delay in dx,
Can give
azathioprine & MTX medication
to maintain remission intolerance
CXR/CT to monitor
response to tx
Disease
Influenza virus
(Orthomyxoviridae)
Clinical Variants
Defining
Characteristics
Incubation period (2d_,
abrupt onset, shedding
of virus 1d before & 5d
after sx begin
HI fever, severe
myalgias, headache,
chills, cough, DOE, GI
sx
Pathogenesis
person-to-person, airborne
transmission of influenza virus
from symptomatic or
asymptomatic hosts
Etiologies
Epidemiology
5-20% of US
population gets flu
each yr; 36,000
deaths/yr (>90%
in people >65 yo)
Risk factors
Elderly
(seasonal flu)
Middle aged
adults (H1N1)
Lab/Imaging
Rapid Antigen
Detection - poor
sensitivity
Viral cx - takes a few
days
PCR (future)
Treatment
Complications
Oseltamivir/Tamiflu
(tx, prophylaxis)
Tamiflu allergy?
Zanamivir/Relenza
EXCEPTION: deaths
from H1N1 were
middle aged adults
primary viral
pneumonia,
secondary bacterial
pneumonia, otitis
media, Reye's
Syndrome (aspirin
+flu), myopericarditis,
?encephalitis
Disease
Clinical Variants
Parainfluenzae virus
(Paramyxoviridae)
Defining
Characteristics
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Laryngotracheobronchitis
(Croup)
Treatment
Complications
No specific antiviral
no vaccine
supportive care
bronchiolitis,
bronchopneumonia,
bronchitis in older
children/adults
community
outbreaks in late
fall to early
spring
Adenovirus
elderly,
immunocomp,
young children
Molecular detection w/
PCR
Cx less valuable
Infection control
because virus may not
be shed for years after Antiviral therapy
inf
cidofovir for
disseminated sx
direct antigen assay
for conjunctivitis
PCR
Immunocomp:
pneumonia,
gastroenteritis,
hemorrhagic cystitis,
hepatitis, interstitial
nephritis
Common cold
Ribavirin
hi secondary
(aerosolized form for infection rates
infants, oral form for
transplant pop)
inhaled form of
ribavirin can cause
supportive care
bronchospasms in
transplant pts
significant resp
pathogen in
transplant pop
Human
metapneumovirus
(paramyxoviridae)
Rhinovirus
(Picornaviridae)
circulate in spring,
summer, early fall
PCR
Coronavirus
circulate in fall,
winter
PCR
Disease
Sleep apnea
Clinical Variants
Central Sleep Apnea
Defining
Characteristics
Pathogenesis
Chronic hypoventilation =
impaired CO2 drive since have
hi PaCO2 levels = cyclical sleep CHF (CheyneStokes,inc
onset central apnea ( apnea
feedback delay)
time, arousal)
Cheyne-Stokes
respiration
Etiologies
hi altitude (longer
periods of sleep
apnea)
Increased
hypersensitivity/
loop gain (from
oversensitive
medulla,
exaggerated output
to resp muscles, or
overefficiency of
lungs in gas
exchange)
Obesity (narrow
airways), large
neck, thick tongue,
URIs, nasal trauma
negative
oropharyngeal
press (small
pharyngeal cavity,
hi pharyngeal
compliance,
decreased upper
aw muscle activity)
Risk factors
Lab/Imaging
Treatment
Complications
hypercapnia,
chronic
hypoventilation
Epidemiology
treat underlying
conditions (CHF CPAP mask)
20 million
Americans, many
undiagnosed; 95%
of all sleep apnea
MRI: narrowed
CPAP (changes
30% noncomplicance
pharynx behind tongue negative airway
to CPAP
pressure to positive,
STOP BANG
so distends the
questionnaire
pharynx during
(Snoring, Tired,
inspiration)
Observed apneas,
Pressure - HTN,
pharyngeoplasty
BMI>35, Age>50,
(effective in 50% of
neck circumference,
pts but very painful,
gender -male) last resort option)
increased risk for OSA
if 3/8 factors
mandibular
advancement
devices (makes
snoring difficult by
holding tongue down)
weight loss
Screening / Education
Screening / Education
Screening / Education
SMOKING
CESSATION!!!
Reduction of risk
factors, flu vaccine
Screening / Education
asthma control
parameters? No daytime
sx (<2x/wk), no limitation
of DALYs/exercise, no
nocturnal sx, no need for
reliever tx (<2x/wk),
nl/near nl lung fx, no
exacerbations
mandatory patient
education and
environmental control;
comorbidity treatment
high level therapy then
step down
Screening / Education
Screening / Education
Screening / Education
Screening / Education
Prognosis? Class I (no
limitation w/ exertion),
Class II (mild limitation
but no probs at rest),
Class III (marked
limitation of activity),
Class IV (no physical
activity possible)
Screening / Education
Screening / Education
Screening / Education
Screening / Education
DVT prophylaxis
(intermittent sequential
compression device adherence issues; anticoagulation - LDUH,
LMWH heparin, factor Xa
inhibitors)
Screening / Education
Prophylactic treatment for
close contacts
RSV prophylaxis
(Synagis) - monthly IM
injections during RSV
season, $$, given to
children who meet certain
criteria (infants born <28
wks gestation, those
born 29-32 wks
gestation during RSV
season, those born 3236 wks gestation & risk
factors - daycare,
school age siblings; full
term kids < 2y.o. w/
CLD, CF, CHD)
Screening / Education
Screening / Education
Screening / Education
Screening / Education
23 valent
Polysaccharide vaccine
- T cell independent (no
memory produced, not
fully functional in infants) used in older children/
adults with risk factors; all
adults > 65
Protein conjugate
vaccine - T cell
dependent (effective
memory cell response;
better at protecting
against localized dz;
reduces carriage in kids);
13 valent conjugate for
routine infant use and
adults > 50 years old
Screening / Education
Screening / Education
Screening / Education
HIV testing to ALL pts
with TB
Start ARVs ASAP (w/I 2
weeks) for HIV+ pts
SCREEN ALL CLOSE
CONTACTS w/ TST
(requires 2 tests, cross
reacts with BCG vaccine)
or IGRA (does not crossreact with BCG vaccine;
single step so better for
homeless)
TST cutoff: 5mm= HIV,
immunodef, contacts w/
TB inf indi; 10mm =
immigrants, HCWs, IDU;
15mm = nl
IGRA = IFN-y release
assay (T cells, if exposed
to TB Ags, will release
IFNy if inf)
Screening / Education
Screening / Education
Inactivated split vaccine
(trivalent) - one A H3N2,
one A H1N1, one B strain
- contraind w/ allergy to
chicken eggs or
Guillian Barre
Live attent Nasal spray
mist (better mucosal
immunity) - contraind in
people w/ reactive aw
dz or pregnancy
vaccination for
everyone >6m
Fluzone Hi dose - new
vaccine for pts > 65 y.o.
(4x dose & greater
efficacy)
Vaccinate HCWs!!
Screening / Education
RSV prophylaxis
(Synagis, mAB) - high
risk infants/premies
Screening / Education
Disease
Left to right
Atrial septal
shunts
defect
(oxygenated
blood flows thru
a defect)acyanotic!
parasternal impulse
(severe); fixed splitting of
S2 (inspiration &
expiration); diastolic
murmur at tricuspid
(severe)
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
diastolic
murmur across
tricuspid;
systolic
murmur across
pulmonic =
more severe
Treatment
Complications
septal occluder
usually closes
spontaneously by
age 10-12; if not,
clamshell occluder
if small,
asymptomatic; if
large, pt will have
dyspnea, slow
growth, shunt
reversal (cyanotic;
Eisenmengers); HF,
IE
Patent ductus
arteriosus
Right to left
shunts
(de-oxy blood
flows into
systemic circ)cyanotic!
Patent foramen
ovale
4 parts:
1. LARGE VSD
2. PS (RVOT obst)
3. RVH
4. AO override
Eisenmenger
Vascular/
Valvular
congenital
disease
Bicuspid aortic
valve
pulmonic stenosis late peaking systolic
murmur
parasternal lift
big "a" wave
Down
syndrome;
maternal alcohol
intake;
trauma/MI
(muscular
defect)
rubella,
premature birth,
high altitude
HF, Eisenmengers
(deoxy blood in left
heart from PA -->
aorta movement
causes PA
hypertrophy = inc
PA press = unoxy
blood in left heart =
cyanosis)
Angiogram: blood
moves from PA
into aorta
increased right
heart pressure
(valsalva,
exercise)
pushes more
blood across
PFO & into LA!
septal occluder
CXR: hyperlucent
lungs (lack of blood
getting to the
lungs)
L-->R shunt that eventually reverses to R->L (acyanotic --> cyanotic shunt w/
increased pressure)
central cyanosis,
clubbing,
hypoxemia, growth
retardation,
polycythemia
(thrombosis, CVA),
PH, paradoxical
embolus
Disease
Tachycardia
Sinus, atrial,
ventricular
HR > 100bpm
no atrial activity so
immediate loss of 20-25%
of cardiac output, grossly
irregular, rapid rate (110180)
asymptomatic
systolic BP
Pathogenesis
Age (vessels
stiffen, need
more pressure
PE: normal position apex,
for blood flow)
different contour to apex
Idiopathic
(95%)
pre-hypertension (120Coarct (5-7%),
139/80-89)
white coat
high pressure in aorta = obstruction after
Stage 1 (140-159/ 90-99)
effect,
Stage 2 (>160/>100)
aortic valve = LVPO = LVH = increased
medications,
incidence of MI & atherosclerosis
alcohol, salt,
PE: BP in BOTH arms,
decreased K or
decreased aorta complicance (stiffer aorta) Ca intake,
check weight/ waist
circumference, fundoscopy, [inc systolic BP = inc pulse wave velocity insulin
from loss of elasticity; dec diastolic BP =
bruits, heart/lung/neuro
resistance,
loss of elasticity = stiffened LV = less
exams;
sedentary
S4 (LVH causes decreased ventricular relaxation]
lifestyle
LV cavity size so atrial kick
needs to push more blood
in), sustained apical
impulse
Hypertensive
Emergency
Epidemiology
Secondary (about
5% of HTN)
Malignant
Hypertension
Etiologies
Renal disease,
accelerated mild
HTN
Cocaine!
60 million
Americans
Risk factors
Lab/Imaging
Treatment
Complications
Thrombi/ emboli
formation
pre-hypertension?
Lifestyle mods
(less salt, exercise,
diet); modify risk
factors (smoking,
obesity, lipidemia,
diabetes)
hard to treat bc
systolic BP is less
likely to decrease,
while diastolic BP
quickly goes down
w/ meds (causes
syncope)
damage to target
organs
MI, atherosclerosis,
aortic dissection,
stroke,
retina/kidney
changes
Disease
Pathogenesis
Etiologies
Epidemiology
uncontrolled
HTN (95%),
bicuspid aortic
valve, Marfan's,
AMA pregnancy,
Turner
syndrome,
coarct
Risk factors
cocaine,
pregnancy
Lab/Imaging
EKG
CT w/ contrast
TEE (intimal flap)
CXR (wide
mediastinum bc
now have 2 aortic
lumens --> aortic
dilation)
Treatment
Complications
nitroprusside
(lowers BP) & beta
blockers (lowers
shear stress) until
EMERGENCY
surgery
50% of patients w/
proximal AD will die
w/I 48h
bleeding into
pericardium, infarct,
shock
distal dissection
Aortic
transection
Abdominal
Aortic
Aneurysms
(AAA)
Peripheral
Vascular
Disease
AR, pericardial
effusion w/
tamponade
trauma
Marfan's,
syphilis,
idiopathic,
atherosclerosis
(cholesterol +
angiotensin II)
Atherosclerosis 10 million
Americans; 5%
of people > 55
claudication - blood supply is limited due to
have
ischemia so pts have calf pain w/ exercise claudication
-> rest pain --> ulceration --> gangrene -->
limb loss
Endovascular
repair (catheter
based, stent
material), open
surgical (graft
material)
progressive
aneurysm
expansion despite
tx
Duplex US:
increased stenosis
& velocity; used to
check intervention
success
risk factor
modification,
aspirin, control of
DM/BP/ chol,
exercise
life expectancy
reduced 10 years
in patients w/ PVD
CT angiography:
anatomic vessel
narrowing
ACEI, antiplatelet
(aspirin,
clopidogrel)
aneurysm >5cm =
increased risk of
future treatments: mortality
external polymer + (PERFORM
doxycycline to
SURGERY!!)
provide
mechanical
risk of surgical
support and inhibit repair? Damage to
MMPs
spinal arteries -->
spinal ischemia/
paralysis
amputees
(asymmetric
reversal of
blood flow)
tobacco use, hi
chol, HTN,
DM, obesity,
sedentary,
male gender,
age
surgery:
endarterectomy,
bypass,
thrombectomy,
ligation; catheterdirected
Disease
Carotid Artery
Disease
Pathogenesis
Etiologies
Epidemiology
Risk factors
recent MI
unstable
angina
uncompensate
d CHF
severe valvular
dz (aortic
stenosis)
Lab/Imaging
duplex US:carotid
artery bifurcation
CT angiograph stenosis of carotid
Treatment
symptomatic:
treat/ surgery if
stroke involves
<1/2 or 1/3 of
hemisphere;
asymptomatic:
operate once
stroke risk >
surgery risk
Complications
Meds: statins,
plavix, BBs
shunt use if
incomplete circle of
surgery: carotid
Willis? only if
revascularization + seizure or loss of
patching
neuro capabilities
perioperative
Endarterectomy higher MI rate
Stenting - higher
stroke rate
Coarctation
Aortic
regurgitation
(AR)
Acute AR:
sudden large
regurgitant
volume on nl LV
= no
compensation
time for
noncompliant LV
= hi LVEDP (LV
dilation) = early
closure of MV =
low SV = hi HR
Turner
syndrome
problem w/
aortic root that
Abnl regurgitation of blood from aorta to LV pulls leaflets
apart (acuteoccurring during diastole (retrograde
AD, aortic
diastolic flow =loss of isovolumic
transection;
relaxation = LVVO >> LVPO) --> higher
preload, somewhat higher afterload (hence chronic Marfan's, Aortic
the mildly hypertrophied LV too per
aneurysm,
LaPlace's Law) = higher LV contractility
syphilis)
(SV), compliance, & wall stress
DIASTOLIC PROBLEM
problem w/ AV
leaflets (acuteendocarditis,
trauma; chronic bicuspid valve,
rheumatic HD,
AV prolapse)
CXR: enlarged LV
silhouette,
enlarged aortic
bump (chronic AR
only); no cardiac
silhouette & pulm
edema (acute AR)
EKG: enlarged LV
(LVVO)
ECHO: degree of
AR (backwards
diastolic flow) +
cause usually
Cath: rapid
decrease in aortic
pressure
HTN
ACUTE AR =
surgical
emergency!! Use
vasodilators
(nitroprusside;
decrease
afterload) while
waiting
CHRONIC AR =
reduce afterload;
surgery if
symptomatic
Disease
Aortic stenosis
(AS)
Mitral
regurgitation
(MR)
subvalvular
(HCM,
membranous AS,
narrow LVOT);
supravalvular;
VALVULAR
Pathogenesis
Etiologies
increased age,
bicuspid valve,
rheumatic heart
dz
SYSTOLIC PROBLEM
Retrograde systolic flow from LV to LA = hi
LAP + hi LA volume = hi LV volume when
blood pumped backwards returns to LV
during diastole = pure LVVO (hi LVEDV,
NO afterload) = loss of isovolumic
contraction
CHRONIC MR: Compensatory
mechanisms = eccentric hypertrophy (LV
dilation + some LVH) = higher
compliance (LVEDV w/o LVEDP) = early
effect of higher SV and EF; eventually LA
dilates = prevention of hi PAP but
decreases CO --> Afib +/- thrombi
ACUTE MR: non-compensated LV so
regurgitated blood goes all the way back
towards lungs --> pulm edema
Epidemiology
Risk factors
mild AS:
>1.5cm
mod AS:
1.0-1.5cm
severe AS:
<1.0cm, mid to
late systolic
murmur
a/w coarct in
Turner's
syndrome,
mitral annular
calcification,
heart block
(conduction
probs), aortic
diss (w/
bicuspid AV)
MV apparatus
parts:
1. annulus
(aging, HTN)
2. LV dilation
(large distance
from pap
muscles)
3. leaflets (MVP,
RHD,
endocarditis,
SAM in HCM)
4. chordae
tendonae
(trauma,
endocarditis)
5. papillary
muscles (MI,
rupture, dilated
CM)
Lab/Imaging
Treatment
CXR: acute MR
(pulm edema),
chronic MR (LV +
LA enlargement)
EKG: LA
enlargement + LVH
ECHO: MR cause
+ severity grade
Cath: acute MR:
large v wave =
increased PCWP =
increased LA
pressure
decrease
afterload, surgical
repair/replacement
for chronic MR
acute MR:
nitroprusside,
EMERGENCY
surgery
Complications
Disease
Mitral stenosis
(MS)
mild MS area
>1.5cm; severe
MS area <1.0cm
Pathogenesis
Etiologies
Epidemiology
Rheumatic
Heart Disease
obstruction to flow from LA to LV, impeding (remember
LA emptying (hi LAP) and causing impaired CANCER
mneumonic;
LV filling (hi LVEDP)
Carditis,
Arthritis,
symptoms from LA distensibility (small
Nodules,
thick-walled LA = inceased pressure =
Chorea,
dilation of LA = increased volume
Erythema
migranatum,
Rheumatic
fever)
DIASTOLIC PROBLEM
Mitral Valve
Prolapse (MVP)
Tricuspid
Regurgitation
acute - infective
endocarditis;
chronic - RHD,
carcinoid
syndrome
RHD, carcinoid
syndrome, RA
myxoma
Tricuspid
Stenosis
pulmonary
hypertension
from MS or RHF
extremely rare!
Risk factors
Lab/Imaging
Treatment
Complications
Pathology: fused
commissures
CXR: LA
enlargement,
interstitial edema,
Kerly's B lines
(pulm edema),
prominent pulm
arteries
EKG: LA
enlargement w/
possible Afib, RV
hypertrophy if PAH
developed
Echo: thickened
mitral leaflets +
abnl fusion of
commisures,
possible intra-atrial
thrombus
ECHO: posterior
displacement of
one or both mitral
leaflets during
systole
Disease
Pulmonic
Stenosis
Pulmonary
Regurgitation
Left ventricular
hypertrophy
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Treatment
Complications
congenital
(Tetralogy of
Fallot), carcinoid
syndrome
severe PAH,
congenital
increased pressure overload on LV causes HTN
increased wall thickness and decreased LV AS
cavity
HOCM
coarctation
Pregnancy,
exercise (nl)
Diastolic
dysfunction (thick
ventricle walls =
decreased
compliance = small
cavity = decreased
filling during
diastole!)
myocardial ischemia
(decreased
coronary blood flow)
systolic dysfunction
(late! Due to
narrowed pulse
pressure)
Peripartum
cardio-myopathy
(PPCM)
No pre-existing heart
disease; presentation
during last month or
postpartum
cough, dyspnea, fatigue
PE: JVD, tachycardia,
S3/S4, +/- edema
postpartum
thyroiditis
1/3000-4000
pregnancies
AMA,
ECHO
multiparity,
CXR
multiple
thyroid panel
gestations,
obesity, HTN/
pre-eclampsia,
tocolysis w/ bagonists
standard heart
highest mortality in
failure mgmt; anti- 1st 3 months
coagulation until
pregnancy ends
LV thrombi (1/8 risk)
--> stroke
Disease
Acute
Pericarditis
Pericardial
effusion
Serous (scant
cells; early acute
inflammatory
pericarditis)
Fibrinous
(plasma proteins
+ thickened/
fused visceral &
parietal
pericardium;TB/
chronic inflamm)
Purulent
(uncommon,
bacterial inf)
Hemorrhagic
(bloody
pericardial
inflamm due to
TB, aortic
dissection, tumor,
trauma, uremia)
Pain is worsened w/
position (lying down)/
expiration/ swallowing
pericardial rub + soft
heart sounds
pain relieved by leaning
forward
Symptomatic - accumulate
lots of fluid quickly under hi
press (chest trauma);
asymptomatic - accumulate
fluid slowly so that
pericardium stretches w/o
marked increase in
pressure
Pathogenesis
Etiologies
Silent or symptomatic?
1. volume of fluid
2. rate of fluid accumulation
3. compliance of pericardium
Epidemiology
Risk factors
Lab/Imaging
Treatment
ATRIUM
(A = AIDS/ Autoimmune dz, T =
tumor/ trauma/
TB; R =
Radiation/
rheumatic fever;
I = idiopathic/
inf/ infarct; U =
uremia from
renal failure; M
= meds)
EKG: diffuse ST
elevation that
disappear as
patient recovers;
diffuse T abnl that
persist for some
time
ECHO: +/pericardial effusion
post-MI pericarditis
(tx w/ hi dose
aspirin)
idiopathic,
malignancies,
radiation, viral
causes, TB
Fluid analysis to
R/O malignancy
treat underlying
disorder (dialysis
for uremia)
TTE: pericardial
collections
(quantifies volume
of fluid, determines
if ventricular filling
is impaired, &
guides pericardiocentesis)
NSAIDS,
colchicine if
chronic pericarditis
Observe
asymptomatic
effusions
pericardiocentesis
for therapeutic
drainage &
analysis
EKG: electrical
alternans (QRS
pericardial window
complex height
procedure
varies from beat to
beat)
Complications
Disease
Cardiac
tamponade
CC: breathlessness
(decreased CO & max
increased EDPs =
increased press in alveoli);
low output state (shocklike), hypotension,
tachycardia
Pathogenesis
Etiologies
any cause of
acute
pericarditis can
progress to
tamponade
(ATRIUM);
acute
hemorrhage
(acute
ascending aortic
dissection, blunt
trauma, LV
rupture)
TTE: smaller,
compressed, &
collapsed RV
during diastole
chronic changes
from
inflammation;
idiopathic
pericarditis (postviral); radiation,
TB, RA,
bacterial inf
Pathology:
pericardial
pericardium
stripping surgery
becomes
immovable shell w/
fused/ thick layers
from chronic
inflamm
BECK'S TRIAD:
Hypotension, increased
JVP (elevated venous
pressure; deep "x", flat
"y" - decreased filling of
ventricles), muffled heart
sounds
Epidemiology
Risk factors
Lab/Imaging
catheterization =
gold standard
Treatment
Complications
Pericardiocentesis;
pericardial window
procedure
(removal of
pericardium
allowing fluid to
drain freely into
mediastinum *
absorbed by
lymphatics;
simultaneous bx)
life-threatening
emergency!! (if
worsens, there is no
filling during diastole
= zero CO =
pulseless arrest)
pulsus paradoxus
(decreased systolic BP of
>10 w/ inspiration)
Constrictive
pericarditis
deep Y descent;
pressures are equalized
& elevated (LVEDP =
PCWP = PAP= RVEDP =
RAP)
cirrhotic appearance
(ankle/leg edema, ascites,
hepatomegaly);
tachycardia, hypotension,
decreased pulse pressure,
inc CVP, Kussmaul (inc
JVP w/ inspiration),
difficult to find PMI, early
to mid diastole knock
Arteriosclerosis
Medial calcific
sclerosis
CXR: calcified
pericardium
Catheterization:
elevation &
equalization of
pressures, dip &
plateau in early
diastole, y descent
in RA, discordance
in RV & LV
pressures w.
inspiration
calcification of the tunica media, the
muscular coat of the artery
intermittent
episodes of
HTN?
marker of HTN;
common in
diabetes
Disease
Atherosclerosis
Pathogenesis
Etiologies
Epidemiology
Risk factors
fatty streaks
seen in 50% of
teens and >85%
of people over
age 20
localized flow
abnl, increased
LDL, HTN,
smoking,
diabetes (all
increase ROS
and decrease
NO)
age
male gender
AS
Lab/Imaging
pathology: gross
large arteries
(yellow spots =
foam cells; fatty
streaks; friable
cracks/ fissures)
stress test: ST
depression
(ischemia) & area
of ischemia
(suggests anatomic
stenosis)
Resting EKG
CT angiography
Cardiac cath if +
stress test
Complications
myocardial
ischemia,
claudication; sites
for thrombus
development (mural
thrombus in aorta
common in HTN,
smoking men);
abdominal aortic
aneurysm
histology: clear
cells in intima (fatty
streaks - early
lesions), bubbly
foam cells;
histiocyte giant
cells surround
cholesterol
crystals; new
matrix being
deposited;
muscular arteries fibrous cap & lipid
pool (stable v.
unstable plaques)
histology:
increased
proliferative SMCs
and fibrous tissue;
does not look
vulnerable bc lipid
core is far from
lumen & thick
fibrous cap
Treatment
if top of plaque
ruptures, lipids are
released into
circulation and
activate
thrombosis -->
ischemia, MI
other complications
if embolization of
plaque material
Lifestyle
modification, PCI,
CABG, medical
therapy
PCI if intolerable
angina despite
maximal med tx &
anatomy that
doesn't require
CABG; older ptshi risk for CABG
MI @ sites of
unremarkable
lesions
single occlusion =
diffuse disease
CABG decreases
risk for rpt
interventions
Disease
Unstable angina
pectoris
Pathogenesis
Etiologies
Epidemiology
Risk factors
500,000
deaths/yr in U.S;
250,000 die
before reaching
hospital
DM, HTN,
smoking,
lipidemia, age
(although 10%
of MI in
age<40)
most common MI
6am-11am
(catecholamine
s are highest
and platelets
stickiest!)
Lab/Imaging
Treatment
Complications
variable
progressively worse sx & frequent plaque rupture with thrombus
formation; partially occlusive thrombus stenosis
pain more
frequent/intense w/ less
starts as lumen compression w/ little lipid
exertion
core but grows with lipid deposit increasing
persistent, unrelenting pain -->thin fibrous cap-->subject to rupture-->
thrombus formation--> vulnerable plaque
for several hours (due to
contributing to MI, sudden death
rupture plaque)
Rupture? thin fibrous cap, increased
inflammatory cells, fewer SMCs, large lipid
deposits, eroded endothelium
Transmural MI
atherosclerotic
CAD (90%),
coronary artery
heart perfused by coronary arteries
vasospasm
from outside --> inside
(cocaine),
coronary artery
emboli;
exacerbations myocardial
hypertrophy,
shock, anemia,
tachycardia
entire thickness of
disruption of
variabe stenosis but unstable plaque
ventricular wall affected by with disruption & consequent occlusive endothelium
the MI
thrombus forming on the plaque -->
atheromyocardial wall damage
chest pain, weak rapid
sclerosis
pulse, dyspnea,
1. disruption of plaque
diaphoresis
2. fissure/cracking of plaque exposes
non-atheroscl
thrombogenic areas (collagen, vWF, FN) causes:
3. platelets adhere, becoming activated
arrythmia,
and aggregated
coronary art
4. coagulation cascade is activated
vasospasm,
(fibronogen --> fibrin via thrombin)
coronary art
5. occlusive thrombus forms
emboli, anemia,
6. downstream ischemia --> depletion of
hypotension,
ATP --> loss of contractility --> irreversible CABG, coronary
cell injury (20-40min; not all cells affected stent thrombosis
equally - epicenter cells > peripheral cells) -> microvascular injury (>1h)
imbalance of O2 supply and demand
Subendocardial
MI
ischemic
cardiomyopathy
most susceptible to
ischemia bc farthest away
EKG: deep Q
waves; ST abnl
(STEMI, NSTEMI)
prognosis depends
on infarct size,
site, extent; quality
of LV fxn, extent of
labs: elevated CK- vascular disease,
mb & troponin I/ T ability to perfuse
viable myocardium
0-12h no changes;
24h (dark mottling; first medical
coag necrosis contact time to
loss of nuclei)
balloon!
1-3d (mottling w/
yellow center;
neutrophils)
3-10d (red border,
yellow center/
neutrophils &
macrophages)
14d (red-gray/
granulation tissue)
>3m (scar)
EKG: do not
always elicit
changes; non-Qwave MI
elderly patients
30% overall
mortality- 1st year
RV infarction
infarct extension new necrosis next
to the infarct region;
infarct expansion dilation of infarct
region; contractile
dysfxn, arrythmias,
pericarditis,
myocardial rupture
(highest risk 4-7
days post-MI; most
often at vent free
wall, also vent
septum - L-R shunt& papillary muscle acute MR), vent
aneurysm, mural
thrombus, pap
muscle dysfxn, late
CHF
Disease
Sudden death
Dyslipidemia
Pathogenesis
(General)
Epidemiology
pediatric presentation w/
chronic abdominal pain
(pancreatitis),
hepatomegaly, xanthomas
abnl high LDL
(heterozygote LDL > 200;
homozygotes LDL > 500)
cutaneous manifestations
(xanthelasma, corneal
arcus, thickened Achille's)
Risk factors
Lab/Imaging
autosomal
dominant
mutation in
LDLR
1 in 500
homozygous
FH patients
have more
severe risk &
dz (little or no
LDLR)
no specific
mutation testing
but cascade
genetic testing for
family risk
assessment impt
autoimmune dz
(SLE, RA,
dermatomyositis),
meds/toxins,
infections
Histology:
fibrinoid necrosis
&
leukocytoclastic
vasculitis
(neutrophils!)
premature vascular dz
Vasculitis
(General)
Complications
increased LDL:HDL
predicts higher risk
for CV event
DIET, genetic
errors of
metabolism,
metabolic
causes (insulin
resistance pre diabetes;
hypothyroidism
hormones),
drug side
effects,
smoking
Treatment
lethal
arrhythmia; nonatheroscl
causes
(congenital abnl,
AS, MVP,
myocarditis,
dilated CM,
hypertrophic
CM, PH,
conduction abnl,
isolated
hypertrophy)
secondary
causes?
Diabetes,
hypothyroidism,
liver dz, kidney
dz, progestins/
steroid drugs
Familial Hypercholesterolemia
Etiologies
Disease
Cutaneous
vasculitis
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Treatment
Complications
Giant cell
(temporal)
arteritis
scalp pain/tenderness
distributed along
temporal artery, visual
disturbances/blindness (if
opthalmic a involved),
polymyalgia rheumatica
in upper neck/shoulders
elderly patients
(>60 y.o.),
females 3:1
high dose
corticosteroids for
months (reduce
inflammation and
prevent
subsequent
sequelae)
Elevated ESR/CRP
more common in
Asia, patients <
40 y.o.,
Females 7:1
histology: NO
NEUTROPHILS,
mostly
histiocytes &
lymphocytes
granulomas
(cannot be
distinguished from
temporal arteritis
histologically)
Elevated ESR
polyarteritis
nodosa (PAN)
HepB
elevated BUN or
creatinine, HepB
antigen, ANCA
negative
histology:
necrotizing
vasculitis of
medium sized
vessels
unpredictable
course: rapid
progression +
quiescent stages
Disease
Pathogenesis
multisystemic sx
(polymorphous skin
eruption, erythema of
conjunctiva/oral
mucosa/tongue
"strawberry tongue",
cervical
lymphadenopathy, edema
in hands/feet,
desquamation of
fingertips/toes)
Etiologies
may be a/w
strep/ staph
infection
Epidemiology
Risk factors
pediatric
presentation
Lab/Imaging
anti-endothelial
antibodies
ANCA negative
middle aged;
males 3:2
pathology: cavitary
lesion in lung
UA: hematuria,
red cell cast in
urine
c-ANCA positive
(proteinase-3)
other multisystemic
manifestations?
Cutaneous, middle ear,
peripheral nerves, CNS,
ocular, oral cavity (midline
destructive lesions)
approximately 50%
of cases will have
CV involvement
MI in kids!!
ELK: Ear/nose/throat
(URI, saddle nose
deformity), Lung (cough,
hemoptysis, cavitary
necrotizing lesions),
Kidney involvement
(hematuria, proteinuria)
Allergic
granulomatosis
(Churg-Strauss)
IV IgG and
aspirin to reduce
inflammation and
avoid sequelae
Complications
CV INVOLVEMENT!
(myocarditis --> CHF,
coronary vasculitis -->
ischemic dz/infarct,
aneurysms)
Wegener's
granulomatosis
Treatment
histology:
vasculitis w/
necrotizing
granulomatous
inflammation
Young adults;
M>F
history of
asthma or
allergic
rhinitis
peripheral
eosinophilia,
elevated ESR
p-ANCA positive
histology: vasculitis
w/ necrotizing
granulomatous
inflammation &
abundant
eosinophils,
involves dermis &
subcutis
(cutaneous only
involves superficial
layers)
Disease
HenochSchonlein
purpura
Pathogenesis
Multisystemic disorder
(cutaneous purpura w/
leukocytoclastic vasculitis,
abdominal pain - bloody
stools, melena; arthalgias,
renal glomerulonephritis)
Etiologies
Epidemiology
possibly
children <10
infection or drug y.o., M>F
related
Risk factors
Lab/Imaging
Immunoflourescenc
e: IgA deposition
in vessel walls
ANCA negative
UA: hematuria,
proteinuria
histology:
leukocytoclastic
vasculitis of
superficial skin (not
specific)
Microscopic
polyangitis
possibly
Adults
infection related
(strep), drug
related?
Elevated ESR,
anemia, renal
failure
UA: hematuria,
proteinuria
Multisystemic vasculitis
(cutaneous purpura,
abdominal pain,
pulmonary involvement!!!
- hemoptysis,
intrapulmonary
hemorrhage, renal
glomerulonephritis,
myalgias)
pulmonary involvement
distinguishes from PAN
Cocaineassociated
vasculitis
ear vasculitis
COCAINE
contaminant
(levamisole)
elevated serologies
common in cocaine
abuse (antihistones, c-ANCA
& p-ANCA, dsDNA)
- human neutrophil
elastase cross
reacts w/ ANCA
impt to do urine
drug screen!!
Histology:
leukocytoclastic
vasculitis, focal
thrombosis
Treatment
Complications
Disease
Heart failure
(General)
3 characteristic
sx:
1. impaired CO
(weak pump)
2. venous
congestion
3. overall fluid
retention
def: inability of
heart to pump
blood forward to
meet metabolic
oxygenation
demand of
tissues while
maintaining nl
filling pressures
backwards!
Systolic heart
failure
dyspnea, orthopnea,
PND, PM dry cough;
stomach/ liver
congestion (early satiety,
anorexia, n/v), edema
(ascites, pulm edema,
periph edema); cold
extremities (inc
catecholamines=
vasoconstriction = low CO);
tachycardia/pneic
PE: JVD (inc cardiac filling
pressures & volume); rales
(basilar; acute CHF);
pleural effusions (chronic
CHF); distended abdomen/
hepatomegaly; peripheral
edema; S3, displaced
PMI, MR (if severe
dilation)
Pathogenesis
Etiologies
Epidemiology
Ischemic
cardiomyopathy
(atherosclerosis!
!)
5 million
Americans have
CHF, 1 million
hospitalizations/
yr
CAD, HTN,
dilated CMP,
valvular dysfxn
Risk factors
Lab/Imaging
CXR: cardiomegaly
if chronic HF
(cardiac
remodeling)
impaired relaxation =
elevated LVEDP; nl LV
volume, concentric
remodeling, EF > 50%
low CO
conditions
("cold, wet"):
valvular dz,
dilated CMP,
HTN, CAD
triad of meds
(carvedilol - BB;
lisinopril,
spironolactone)
thin walled,
dilated ventricle
Complications
development of
kidney failure (nl
creatinine = 1) most impt
negative
prognostic factor!
hi CO
conditions
("warm, wet"):
hyperthyroidism,
anemia, AV
fistula, Paget's,
Beri-Beri
decrease afterload
= improved SV =
less ischemia; =
reduced preload =
reduced
remodeling
Diastolic heart
failure
Treatment
hypertensive
CMP, HOCM,
amyloidosis
hypertrophied,
enlarged,
thickened
cardiac
myocytes
increased
prevalence w/
age
requires clinical
evidence of
impaired RV
relaxation or LV
passive stiffness:
no treatment, just
symptom relief
be careful w/
diuretics (pts have
small/ stiff LVs so
elevated BNP
diuretics can
CXR: pulm edema cause LV
ECHO: R/O other underfilling -->
causes for
hypotension,
impaired LV filling; syncope, falls!)
shows LA
enlargement, nl EF control BP,
ventricular rate &
heart cath = gold rhythm
std but invasive;
use ECHO
instead
presence of
symptoms = worse
prognosis
high comorbidity
burden (usually
elderly patients w/
dHF)
majority of dHF
patients die from
non-cardiac causes
Disease
Cardiomyopathies
Heart failure w/
normal EF
(HFnEF)
(General)
Hypertensive
cardiomyopathy
Familial dilated
cardiomyopathy
increased diastolic
pressure (>85 or 90)
dilated LV (nl 4-5cm)
causes poor systolic fxn
(can barely contract)
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Treatment
Complications
elderly women
w/ HTN, DM,
or both, CAD,
Afib
african
americans
Arrhythmogenic
Right Ventricle
Cardiomyopathy
(ARVC)
1 per 1000-2500
clustering of
cases in Veneto
region of Italy
genetic testing
ECHO: dilated RV
EKG: epsilon
waves in ST
segment (delayed
depolarization)
aneurysms of RV
wall on cardiac
MRI, angiogram
pathology: buildup
of scar tissue;
white and yellow
fibrosis (RV muscle
replaced w/ fibrotic
tissue)
SCD
Ventricular
tachycardia
Disease
Restrictive
cardiomyopathy
sx of CHF (dyspnea,
volume overload, edema)
very difficult to
distinguish from
pericardial constriction
Left Ventricle
Noncompaction
decreased LV function,
increased LV dilation
Pathogenesis
non-dilated, non-hypertrophied LV w/
advanced diastolic dysfxn (thin walled,
stiff ventricle that can't relax during
diastole)
Etiologies
Epidemiology
Risk factors
idiopathic
infiltrative dz
(amyloid,
sarcoid)
prior radiation
Lab/Imaging
Treatment
Complications
Non-neoplastic Thrombi
Cardiac masses
Infective
endocarditis
family history
of HCM/SCD
SAM associatd
MR (systolic
anterior motion
of MV)
1 in 500 adults
LVOT
obstruction
hypercoagulable
states; Afib (or
other rhythm
disorders)
histology:collagen,
myocyte disarray
EKG:
Brockenbrough's
sign (PVC -->
press gradient -->
aortic press drop),
tall QRS, invert T
ECHO: thick LV
wall w/ nl systolic
fxn; SAM of MV;
aortic midsystolic
notching (late
ejection from obst)
Doppler: turbulent
flow (MV
obstruction in
LVOT), possible
MR (MV pulled
open in systole)
Pathology:
calloused IVS from
MV hitting
HR,(-) inotropy
(BB, CCBs,disopyramide)
most common
cause of SCD in
athletes!
(especially if
surgical myectomy- intramural scarring -> Vtach)
remove part of
septum= widen MVseptum gap;
Increased collagen
alcohol septal
= increased
ablation- induce MI arrhythmia risk
in basal septum=
fibrosis/shrinking)
ICD: indicated if
aborted SCD or
sustained VT; 2+
risk factors (FH,
unexplained
syncope, wall
thickness >30mm,
abnl BP drop,
nonsustained VT
Disease
Primary cardiac
tumors
(General)
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
very rare
Treatment
Complications
delayed dx bc mimic
many dz that impair
cardiac fxn
clinical manifestations:
most common pediatric cardiac tumor?
impaired cardiac fxn, fever, Rhabdomyoma
inc ESR, emboli
most common malignant cardiac tumor?
Angiosarcoma
Cardiac myxomas most common primary
tumor
cytokine
associated (IL6)
Carney/LAMB/NAME
genetic syndromes w/
myxomas
10% are
inherited
(multiple
myxomas think Carney
complex/
NAME/ LAMB see below)
macroscopic:
pedunculated
(move w/ position,
pressure) or
sessile (no
movement), can be
bilateral/ multiple
(more likely to be
syndromic), +/calcifications
microscopic:
myxoid (gelatinous)
matrix, variable
cellularity, mucinsecreting cells
genetic
FH
differentiate from
other lentigenescausing
syndromes:
LEOPARD - no
cardiac myxomas
w/ this syndrome:
lentigenes, EKG
abnormalities,
ocular
hypertelorism,
pulmonary
stenosis, gonadal
hypoplasia,
retarded
growth,deafness
embolus (stroke, GI
infarct, distal
toe/finger infarct)
Disease
cardiac
rhabdomyomas
Pathogenesis
Etiologies
Epidemiology
1. angiosarcoma
2. pleomorphic
undifferentiated
sarcoma
3. rhabdomyosarcoma
malignant! vague sx
(dyspnea, chest pain,
tamponade, palpitations),
usually in atria
Angiosarcoma = most
common cardiac sarcoma;
infiltrative mass in RA ,
early mets (usually lungs);
3m survival
pleomorphic undiff
sarcoma: = cell origin is
unknown, occurs in atrium
(commonly posterior
wall), low survival
Rhabdomyosarcoma =
atrial & ventricular lesions,
mimics atrial myxoma,
mean ages affected 2030s; survival 1.5-6m
Lab/Imaging
Treatment
Complications
macroscopic:
circumscribed
ventricular mass
(not encapsulated),
white-yellow &
waxy appearing
Primary cardiac
sarcomas
Risk factors
mean age
around 40 y.o.,
M=F; rare to see
childhood
sarcomas
Macroscopic:
angiosarcoma
(violaceous/
reddish purple
color - blood
forming tumor)
microscopic:
rhabdomyosarcoma has
rhabdomyoblast
(eccentric nuclei +
eosinophilic
cytoplasm)
resection is not
curative
Disease
Pathogenesis
Etiologies
Epidemiology
often asymptomatic
unilateral calf swelling
(large clots overwhelm
lymphatics); calf
tenderness, positive
Homan's sign (inflamed
venous wall), venous
cords
LEOPARD
syndrome
Virchow's Triad: Venous stasis +
venous stasis- 2 million/yr
immobilization,
Intimal (endothelial) injury +
other (age>40,
Hypercoagulable state
varicose veins,
Wells' Clinical Prediction Rule for DVT: severe COPD,
anesthesia, MI,
active cancer (rx<6m) = 1
obesity)
leg paralysis/ immob = 1
endothel injbedridden >3d from surgery = 1
surgery, gen
local tenderness along deep veins = 1
inflamm, prior
unilateral swelling (>3cm), pitting = 1
DVT, central
collateral superficial veins = 1
line, trauma,
alternative dx more likely = -2
**High risk (>3pts), mod risk (1-2pts), low major venous
surgery,
risk (<1pt)
smoking;
hypercoag cancer, hi
estrogen, IBD,
sepsis, blood
transfus, HIT,
primary
thrombophilias
Risk factors
Lab/Imaging
Treatment
Complications
immediated LMWH
or heparin, overlap
with oral
anticoagulation
(coumadin), IVC
filter (if cannot take
anticoag)
chronic swelling,
pain, skin
ulceration, recurrent
episodes of DVT,
pulmonary emboli!
highly
metastatic
cancers?
Melanoma
intermediate
metastatic
cancers?
Breast & lung
cancers, RCC,
leukemia/
lymphoma,
sarcomas
low metastatic
cancers?
Prostate, GI,
hepatocellular,
pancreatic,
ovarian
pregnancy,
male gender,
African
Americans
Disease
Pulmonary
embolism
Pathogenesis
Pulmonary
arterial
hypertension
3. PH w/ lung dz
pulmonary arterial hypertension (primary) PAP > 25 mmHg, normal PCWP (<15;
general pulm hypertension has ANY wedge
press), always elevated transpulmonary
gradient
Etiologies
pulmonary
artery
obstruction;Chro
nic pulmonary
hypertension w/
recurrent
emboli;
paradoxical
emboli (PFO,
ASD); chronic
thromboembolic
dz
stiffened LV
causes inc LA
pressure = inc
PAP (#2)
sarcoidosis,
hyper/
hypothyroidism,
renal dz (#5)
idiopathic (#1)
Epidemiology
3rd most
common CV
illness in US;
25% mortality if
untreated
Risk factors
Virchow's
triad
Lab/Imaging
ECHO: RVPO
(large PE)
spiral CT: best!
Treatment
anticoagulants
Complications
decreased CO and
BP --> Vtach, Vfib
pulseless activity to
heart
thrombolytics
(patient in shock;
If low to int wells - contraindicated in
get D-dimer (if nl - age>80, major
pulm hemorrhage,
done; if abnl - get surgery in pats 7
acute cor pulmonale
CT)
days, major trauma
in 10 days, TIA/
If int to high Wells- CVA, GI bleed in 3
get CT scan (if nl, months, uncont
PE excluded; if
HTN, known
abnl - treat for PE) bleeding disorder)
younger
CXR: enlarged RV,
people, female prominent right
gender (#1)
heart border (RA)
ECHO: dilated
large RV and
flattened septum
compressing LV
Cath: increased
RVEDP, PAP
Pathology (#1):
SMC proliferation
(endothelin) &
vascular
remodeling
#4 is surgically
treatable (pulm
thromboendartectomy)
#2 needs BB,
ACEI, diuretics
nitrates
#1 requires heart &
lung transplant;
CCBs if
vasoresponsive
diuretics to prevent
RHF;
anticoagulants to
prevent clots;
digoxin if
arrhythmias,
exercise,
supplemental O2 if
hypoxic
Screening /
Education
Screening /
Education
5 mm Hg
increase in DBP
or SBP = 2030% increase in
CVD
increased SBP
= decreased
survival
BP monitoring at
home (night BP
nl dips 10-20%;
non-dippers
have increased
risk of CVD)
Screening /
Education
DHHS: screen
men aged 65-75
who have ever
smoked w/ 1x
abdominal US; if
positive, yearly
screening
recommended
Society of
vascular
surgery: screen
all men btwn
age 60-85, all
women age 6085 w/ CV risk
factors, and all
men/women
over age 50 w/
+FH for AAA
with abdominal
US
if you see PVD,
make sure the
patient isn't
going to have a
stroke/ MI - their
legs can wait!
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
50% maternal
mortality w/
subsequent
pregnancies if
CM persists
avoid combined
oral
contraceptives
increased risk of
recurrence!
Screening /
Education
Screening /
Education
Screening /
Education
functional class:
Class I - angina
w/ strenuous ex
Class II - angina
w/ walking or
stairs; or > 2
blocks on level
ground;
Class III: angina
w/ one flight of
stairs or
<2blocks
Class IV: angina
w/ walking
around house or
at rest
BP control;
SMOKING
CESSATION,
weigh reduction,
daily exercise,
lipid mgmt (diet)
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Stages: A = at
risk (DM, HTN,
etc); B =
asymptomatic
ventricular
dysfxn; C =
symptomatic
dysfxn; D = end
stage HF
Can't move
between stages;
but can move
between
functional
classes
Screening /
Education
competitive
sports restriction
common cause
of SCD in
athletes
Screening /
Education
competitive
sports restriction
Screening /
Education
Screening /
Education
Screening /
Education
DVT
prophylaxis mechanical,
medical (anticoagulation!unfractionated
heparin,
LMWH)
Screening /
Education
Disease
Clinical Variants
Defining Characteristics
Periodontal disease
HSV
(General)
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Treatment
Complications
65% of US adult
population
Antibodies in 90% of
U.S. population
Primary Herpetic
Gingivostomatitis
Secondary oral
herpetic lesions
HSV
Young children
Hospitalization for
dehydration
HSV
prophylaxis w/ acyclovir
immunocompromised have
more widespread lesions
?? Not known
20-60% of population
self-resolving +/corticosteroids
surgical + adjunct
radiation/chemo
High SES,
immunocomp
(more severe)
Premalignant oral
lesions
Ulcerative,
exophytic, plaque
like
Leukoplakia
Erythroplakia
Oral/ sinonasal
melanoma
Ameloblastoma
Salivary gland
neoplasm
(general)
VERY common
VERY uncommon
VERY rare compared to
cutaneous melanoma
most common
odontogenic neoplasm
Salivary gland
neoplasm
Disease
Clinical Variants
Pleomorphic
adenoma
Warthin tumor
Mucoepidermoid
carcinoma
Adenoid cystic
carcinoma
Paranasal sinus
neoplasms
Squamous cell
carcinoma
Adenocarcinoma
Gastroesophageal
reflux (GERD)
Barrett's esophagus
Eosinophilic
Esophagitis
Candida esophagitis
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
Risk factors
F>M
M>F
candida
histology: intestinal
metaplasia (columnar
epithelium + Goblet cells +
villus pattern development)
endoscope: salmon colored
mucosa above Zline
uncommon
10% of population
globally; 15-44% of
Americans affected
monthly
diet, obesity, CT
disorders,
CVD/asthma (bagonists), DM
hx of atopy
(asthma, allergic
rhinitis, eczema);
younger men
Complications
smoking!!!
Treatment
varied histopathology
commonly in parotid
most common malignant
salivary neoplasm (60-90%
occur in parotid despite parotid
glands nl having benign lesions)
Lab/Imaging
immunocomp
(HIV, chemo,
chronic steroid
use - asthmatics)
anti-fungals (Fluconazole)
Disease
Clinical Variants
Viral esophagitis
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
Herpes, CMV
Risk factors
immunocomp
(HIV, chemo,
chronic steroid
use - asthmatics)
Lab/Imaging
Treatment
Complications
esophageal
neoplasm
(General)
Squamous cell
carcinoma
Esophageal
adenocarcinoma
GI stromal tumors
(GIST)
6/100,000 in U.S.
GERD, Barrett's
metastasis (middle
esophagus --> mediastinal,
paratracheal LN; lower 1/3
esop --> perigastric, celiac
LNs; upper 1/3 --> cervical
LNs)
Caucasians
histology: no glands;
keratinized/ squamous
pearl;equipotent replicative
ability; mitotic figures, loss of nl
maturation and polarity; chronic
inflamm cells present
gross: white mucosa replaced
by red mucosa from stomach;
firm; oval/long appearance;
ulcerative
mutation in c-kit
bleeding
Small cell carcinoma
Primary esophageal
motility disorders
Melanoma
Achalasia
Endoscopic pneumatic
dilation; botox injection in LES
during endoscopy (short term)
Esophageal varices
Esophageal
lacerations (MalloryWeiss tears)
bleeding (hematemesis)
alcoholic binge
endoscopic sclerosing or
banding
most patients have coexisting hiatal hernia
(stomach slips into
esophageal hiatus)
Disease
Clinical Variants
gastric, duodenal
Defining Characteristics
Pathogenesis
Gastritis
Acute gastritis
Chronic gastritis
Gastric polyps
Adenomatous
Gastric
adenocarcinoma
(General)
Etiologies
Epidemiology
5-10% lifetime
prevalence
Risk factors
Lab/Imaging
Treatment
Complications
H. pylori, autoimmune
gastritis, chronic alcohol
abuse, radiation, post surgical
F>M
Disease
Clinical Variants
Intestinal type
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
older patients w/
known risk factors
Risk factors
Lab/Imaging
Treatment
Complications
Diffuse type
Gastric lymphomas
Gastric carcinoids
MALT lymphoma
Low grade
high grade
symptoms depend on
hormones being produced
often secrete gastrin
M=F
VERY rare
Malrotation
?? Unknown
1% of congenital
population (incidence
ranges from 1/6000 1/200)
majority diagnosed w/ 1
year of life but some go
undetected until
incidental find on GI
imaging/surgery
histology: foveolar
hyperplasia
Upper GI series: No duodenal Ladd procedure (required for
ALL malrotations regardless
C- loop (ligament of Treitz
of symptoms)
doesn't cross the midline)
Intestinal atresia
increased risk of
adenocarcinoma
surgical emergency!!
Congenital
hypertrophic pyloric
stenosis
Disease
Clinical Variants
Hirchsprung's
disease (aganglionic
bowel)
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
1/5000
Risk factors
positive FH
sometimes
Lab/Imaging
Treatment
resection of aganglionic
segments
Complications
lifelong implications
15% of HD babies have
other associated
congenital anomalies :(
anorectal manometry:
differentiates normal v. abnl
functioning bowel by recto-anal
inhibitory reflex
Crigler Najjar
Syndrome
Type 1
Type 2
Elevated indirect
(unconjugated) bilirubin;
benign - asymptomatic
jaundice
elevated indirect (unconjugated)
bilirubin
family history
none
severe/fatal
elevated indirect (unconjugated) reduced UDP glucoronyl transferase
bilirubin;
activity
less severe (Arias syndrome)
neonatal jaundice
(unconjugated
hyperbilirubinemia) -->
kernicterus (toxic
encephalopathy)
Neonatal
hyperbilirubinemia
Viral hepatitis
Hepatitis A
Hepatitis B
poor hygiene,
overcrowding,
institutions,
endemic countries
(Latin America,
Africa, Asia), food
outbreaks
cases in U.S. are usually
immigrants or vertical
transmission to infants
born in U.S. by
immigrant moms
Globally - horizontal
transmission + vertical
400 million carriers in
world (75% in Asia)
surface proteins: HBeAg, HBsAg, HBcAg, transmission
DNA polymerase
test immigrants from
endemic region, MSM,
LONG incubation period; may be
multiple sex partners, IVDU,
contagious up to 15 weeks postinmates, dialysis pts, HIV pts,
symptoms
pregnant women, close
contacts of known cases, pts
w/ abnl liver enzymes
risk of chronicity
determined by age of
infection acquisition
pregnant? Tenofovir in 3rd
(younger individuals w/ Hep
trimester; give infant HBIG + B = hi risk for chronic hep B)
HepB vaccine w/I 12h of
birth
#1 cause for cirrhosis &
HCC globally
anti-HBc = represents natural
infection (either acutely or
chronically)
Disease
Clinical Variants
Defining Characteristics
Hepatitis C
Hepatitis D
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Treatment
Complications
pegylated interferon +
ribavirin
CAN BE FATAL IN
PREGNANT WOMEN!!!
occurs w. moderate-marked
EtOH intake
asymp in most cases
clinical presentation:
hepatomegaly, elevated liver
enzymes
REVERSIBLE!
Alcohol hepatitis
Alcohol-related
hepatic cirrhosis
histology: hepatocyte
swelling/necrosis, Mallory
bodies (bright pink inclusions
representing aggregates of
cytokeratin; also seen in
Wilson's dz & cholestasis),
neutrophilic infiltrate;
possible steatosis & fibrosis
IRREVERSIBLE!!
dose-dependent
(acetaminophen -->
accumulation of
NAPQI)
Adults
obesity
malnutrition
pregnancy
other drugs
alcohol
hx of DILI
genetics
PMH of liver dz
histology: massive/zonal
necrosis, inflammation (if +
eosinophils, think
hypersensitivity), granulomas,
steatosis (microvesicular has
worse prognosis),
phospholipidosis (deposition of
phospholipids in hepatocytes),
SOS (sinusoidal obstructive
syndrome; fibrosis around
highest risk
central vein); more damage in
profile? Obese F zone 3
> 50y.o. who
drinks EtOH
dx of exclusion
monitor LFTs in patients taking
INH
Drug-induced liver
Disease
injury (DILI)
Autoimmune hepatitis
histology: massive/zonal
Lab/Imaging
necrosis,
inflammation (if +
eosinophils, think
hypersensitivity), granulomas,
steatosis (microvesicular has
worse prognosis),
phospholipidosis (deposition of
phospholipids in hepatocytes),
SOS (sinusoidal obstructive
syndrome; fibrosis around
highest risk
central vein); more damage in
profile? Obese F zone 3
> 50y.o. who
drinks EtOH
dx of exclusion
Treatment
Adults
Risk factors
obesity
malnutrition
pregnancy
other drugs
alcohol
hx of DILI
genetics
PMH of liver dz
1/30,000 people
age of onset typically 1525
lifelong chelation
liver transplant is curative
genetic predisposition,
200,000 U.S. patients;
exposure to unk environmental F>M; average age 20-40
factor
Elevated transaminases,
elevated IgG, +ANA/SMA/
liver-kidney microsomal-1
antibodies (1 of the 3 usually)
Primary Biliary
Cirrhosis (PBC)
Primary Sclerosing
Cholangitis (PSC)
autoimmune disorder
characterized by progressive
destruction of intrahepatic bile
ducts (microscopic injury)
5/100,000
F>M
median age of dx 50-55
ursodeoxycholic acid
slowly progressive disease
(synthetic bile acid - 32% risk leading to cirrhosis in 10reduction in death/ liver
20 years
transplantation)
8.5/100,000
M>F
avg age of dx 40
liver transplant!
Disease
Glycogen storage
disease
Tyrosinemia
Clinical Variants
GSD-1
type 1
Defining Characteristics
Pathogenesis
mutation in either GLUT2 or glucose-6phosphatase --> hypoglycemia (glucose-6phosphate cannot be converted to glucose
OR glucose cannot be transported out of
liver for usage)
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Hereditary
hemochromatosis
family history
compensated
Cirrhosis
nutritional management
(continuous night feeding via
ng tube; uncooked corn starch
before bed; frequent feedings)
Alpha1- antitrypsin
deficiency (A1AT)
Complications
Treatment
frequent phlebotomy to
remove RBCs (and hence
drop iron levels)
Disease
Clinical Variants
decompensated
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Cirrhotic changes +
SYMPTOMS
Treatment
Complications
cerebral vasodilation
(hepatic encephalopathy),
peripheral vasodilation
(shock), pulmonary
vasodilation (portopulmonary
hypetension,
hepatopulmonary syndrome,
hepatic hydrothorax),
metabolic/ hemodynamic
derangements
abdominal compartment
syndrome (restrictive lung
physiology)
spontaneous bacterial
peritonitis: > 250
neutrophil count in
pericentesis
hypoglycemia (BAD sign)
Portal hypertension
hepatic
encephalopathy
cirrhosis (increased
resistance in sinusoidal space)
Other causes? Portal/ splenic
vein thrombosis,
schistosomiasis, venoocclusive disease, Budd-Chiari
Infection, GI bleed,
dehydration
systemic manifestations;
splanchnic vasodilation -->
pathologic shunting of blood
away from liver --> increased
Hepatic pressure venous
cardiac output into
gradient (HVPG) = WHVP
splanchnics --> decreased
(wedge pressure) - FHVP (free
effective arterial blood
hepatic pressure); nl 3-5 mmHg
volume --> compensatory
upregulation of
neurohormonal systems
(RAAS, SNS, ADH) --> inc
intravascular volume (renal
vasoconstriction or Na/H2O
retention) --> hepatorenal
syndrome OR ascites/
hyponatremia
serum ammonia level not
eliminate ammonia production reversible with treatment!
sensitive but can use serial
sources using lactulose,
levels to measure treatment
rifaximin, or metronidazole
response
low platelet count
(thrombocytopenia)
hyperammonemic state
different dz manifestations
depending on setting of acute or
chronic liver dz; acute liver dz
(development of intracranial
HTN & cerebral edema -->
herniation); chronic liver dz
(less injury bc upregulation of
ammonia backup systems)
Cirrhotic
cardiomyopathy
Hepatopulmonary
syndrome (HPS)
Disease
Clinical Variants
Portopulmonary
Hypertension
(PPHTN)
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
ECHO (screens) + RH
catheterization (confirms)
CXR
dyspnea, hypoxemia
Variceal hemorrhage
hematemesis, hematochezia
Complications
Diuresis, prostaglandin
therapy if acute RV failure
Liver transplantation does not
immediately reverse PPHTN
(so patients must continue
prostaglandins) - difference
btwn HPS & PPHTN
Hepatic hydrothorax
Treatment
endoscopy
Thoracentesis
respiratory faulure
diuretics
spontaneous bacterial
empyema
TIPS = transjugular
intrahepatic portosystemic
shunt
splanchnic vasoconstrictors
(ocreotide), BB to decrease
HR, empiric antibiotics
Band ligation via endoscopy if
esophageal varices
TIPS if failed variceal banding
or gastric varices
Hepatorenal
Syndrome (HRS)
Annular pancreas
terlipressin (splanchnic
vasoconstrictor)
1/20,000
5-7% of population
Ectopic pancreas
endoscopic or surgical
sphincterectomy, stent
placement
1-2% of population
Congenital pancreatic
cysts
Cholelithiasis
(gallstones)
Cholesterol (80%)
very rare!
surgical resection if
symptomatic
10-15% of men > 60y.o.; age, obesity, child U/S - 98% sensitivity
20-40% of women > 60 bearing, estrogen MRI - better or equivalent to
y.o.
use, OCPs, DM,
U/S
hyperF>M
triglyceridemia,
IBD, terminal
ileum disease,
other
comorbidities
no intervention if
asymptomatic
cholecystectomy + R/O
complications
ursodeoxycholic acid
(secondary bile acid that
reduces chol secretion into
bile)
acute cholecystitis
gallstone ileus
biliary pancreatitis (distal
impaction)
Acute cholangitis
Choledocholithiasis
Mirizzi syndrome
Disease
Biliary colic
Acute Cholecystitis
Clinical Variants
Defining Characteristics
ACUTE cholelithiasis
RUQ/epigastric pain that
radiates to right
shoulder/scapula; worse with
meals, steady pain (15-60min)
that slowly resolves; NL
physical exam (+/- RUQ
tenderness); nl labs;
most common complication of
gallstones
Pathogenesis
Etiologies
Risk factors
Choledocholithiasis
Epidemiology
Lab/Imaging
cholelithiasis
Treatment
Complications
recurrent? Elective
cholecystectomy +/intraoperative cholangiogram
to clear out any stones in bile
duct if needed
gallbladder empyema
perforation (distention,
ischemia, pericholecystic
fluid collection --> abscess)
mild hyperbilirubinemia,
elevated ALP, transient
AST/ALT spike would suggest
passage of stone into
duodenum
ERCP + cholecystectomy
(unless high risk patients these will have ERCP +
URSA to dissolve the stones)
Cholangitis
Gallstone ileus
Mirizzi Syndrome
Irritable Bowel
Syndrome (IBS)
1. IV antibiotics
2. Elective ERCP to remove
stone
EUS/MRCP (regular U/S would 3. PCT if ERCP unsuccessful
miss bile duct stones)
4. cholecystectomy (after
infection cleared and stone is
CT if worried about
out)
complications
remove stone +
hi mortality/morbidity
cholecystectomy
Cholecystectomy + ERCP or
cholangiogram to open the
bile duct
1. reassurance +
lifestyle/dietary mods
2. increased severity? Agents
that treat motility (antidiarrheals, anti-constipation)
3. no response to above?
Psych referral for pain
management
Disease
Acute pancreatitis
Clinical Variants
Defining Characteristics
Chronic pancreatitis
Pathogenesis
Etiologies
alcohol
idiopathic
other (drug induced dideoxyinosine/DDI, 6mercaptopurine/
azathrioprine), iatrogenic ERCP, sphincter of Oddi, high
lipids, infection, pancreas
divisum, autoimmune, CF,
trauma, neoplasm)
Epidemiology
Risk factors
Lab/Imaging
Gallstone pancreatitis?
Elevated bilirubin, liver
enzymes, lipase/amylase,
WBC, + gallstones on
imaging
Acute mesenteric
ischemia
nonocclusive mesenteric
ischemia
Abdominal Aortic
Aneurysm (AAA)
Celiac disease
gluten allergy
a/w autoimmune disorders
(SLE, DM type I, RA, thyroid
disease)
1/100
Irish / European
descent
family history
no damage to pancreas;
majority of patients do NOT
have any complications
Functional: parenchymal
changes denoted by
secretin/CCK test
Acute diverticulitis
Complications
Autoimmune pancreatitis?
Swollen pancreas on CT,
+ANA, +IgG4
Treatment
Disease
Benign liver
neoplasms
Clinical Variants
Cavernous
hemangioma
Hepatic adenoma
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
age, OCPs
Treatment
Complications
Non-neoplastic
hepatocellular
nodules
Hepatocellular
carcinoma
women of
reproductive age
cirrhosis
hemochromatosis
Cholangiocarcinoma
Adenocarcinoma of
gallbladder
Cystic pancreatic
neoplasms
Pancreatoblastoma
serous cystic
neoplasms
mucinous cystic
neoplasms
histology: formation of
haphazard glandular
structures
CIRRHOSIS PATIENTS DO
NOT HAVE INCREASED
RISK!
usually occurs in presence of
gallstones
Female
Females
Female
YOUNG
FEMALES
KIDS!!! (rare
cases in adults,
who would have
worse prognosis)
Disease
Clinical Variants
Pancreatic ductal
adenocarcinoma
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
Pancreatic Acinar
Cell carcinoma
Risk factors
Lab/Imaging
Treatment
Clostridium dificile
Giardia lamblia
(Flagellate)
symptoms: malabsorptive
diarrhea, steatorrhea, cramps,
bloating, nausea, weight loss,
vomiting, fever
ingestion of cysts from environment leds
bloody stools (inflammatory),
to development of trophozoites in large
dysentery
colon --> invasion into epithelia (unlike
Giardia, which is local and stays in
duodenum/jejunum)
Entamoeba
histolytica
Apicomplexa
parasites
Cryptosporidium
parvum
Isospora belli
Microsporidia
Enterocytozoan
bienusi
2% of all pancreatic
tumors
Antibiotic use,
hospital setting,
elderly,
chemotherapy,
surgery,
Ulcerative colitis
metronidazole or tinidazole
[toxicity/ side effect =
disulfuram effect = nausea
and severe symptoms]
daycare centers
metronidazole for
trophozoites; paranomycin
for cysts
malignancy determined by
hormone secreted, size of
tumor, & aggressiveness
Cyclospora
cayetanesis
Complications
global
Nitazoxanide (NTZ)
extra-intestinal
manifestations (amoebic
liver/lung/ brain abscess)
Disease
Clinical Variants
Defining Characteristics
Microsporidia
Strongyloides
stercoralis
Other nematodes
Encephalitozoon
intestinalis
(Nematodes)
Ascariasis
Enterobiasis
Trichuriasis
Hookworm
Cestodes/ flatworms
Blood flukes
Taenia solium
Taenia saginata
Echinococcus
Diphyllobothrium
latum
Schistosomiasis
Liver flukes
Clonorchis sinensis
E. coli
Fasciola hepatica
ETEC (Traveler's
diarrhea)
Etiologies
tropical, subtropical
areas; southern US
whipworm
colitis (bloody stools), rectal
prolapse
major contributor to global
malnourishment
hyatid cysts
vitamin B12 deficiency,
macrocytic anemia
swimmer's itchy, Katayama
fever, chronic dz
increased risk of
Cholangiocarcinoma
RUQ pain, fever, jaundice
occur usually after travel to
resource poor country; shortlived secretory diarrhea
Lab/Imaging
Treatment
serology
IVERMECTIN (binds to
glutamate-gated chloride
channels causing parasite
paralysis & death)
Complications
immunocomp at
risk for
hyperinfection
syndrome
poor sanitation
places
daycare!!!
ALB, MBZ
PORK
BEEF
DOG, SHEEP
FRESHWATER FISH
FRESHWATER
RAW FRESHWATER FISH
WATERCRESS
contaminated food & water
hydration; antimotility
meds; fluoroquinolones
(CIPRO)
typhoid fever
Salmonella
typhimurium
poor sanitation
places
tropical areas
Risk factors
barefeet
ingestion of eggs
Salmonella typhi
Salmonella
enteritidis
Epidemiology
global
Salmonella
Pathogenesis
fungal organisms that produce pathology
when spores are inhaled or ingested
Hemolytic uremic
syndrome (HUS) =
anemia,thrombocytopenia,
renal failure [1wk post
diarrhea; more common in
children, but 12% affected
require dialysis or die from
ESRD]
ANTIBIOTIC TX NOT
decreased gastric acidity
RECOMMENDED in
lowers infectious dose uncomplicated gastroenteritis increased susceptibility
(could increase organism
carriage)
Disease
Food Poisoning
Clinical Variants
Defining Characteristics
Pathogenesis
Etiologies
Epidemiology
Risk factors
Lab/Imaging
Treatment
Rotavirus
rehydration
winter season
Vomiting, fever, watery diarrhea
--> dehydration & electrolyte abnl
Norovirus
Small bowel
obstruction
Large Bowel
Obstruction (colonic)
cruise ships
post-operative intra-abdominal
adhesions; hernias (bowel leaves
peritoneal cavity and becomes
obstructed); neoplasms;congenital
atresia/stenosis, inflammatory causes
PE: periods of increased bowel (IBD, ischemia, diverticulitis, radiation,
drugs), intussusception (bowel telescopes
sounds followed by intervals of
quiet; hi pitched or musical BS; into another part of the bowel); gallstones,
abdominal tenderness; guarding volvulus, metastasis, endometriosis,
abscess
(strangulation/ bowel
ischemia); systemic
manifestions of dehydration
(tachycardia, tachypnea, AMS,
oliguria, hypotension)
Bowel ileus
fecal-oral; aerosol-vomitus;
fomites; contaminated food
cecal volvulus - NO
COLONOSCOPY; cecostomy,
resection
NPO until symptoms resolve;
NG tube; correct electrolytes;
limit narcotics; get patient
moving out of bed!
Complications
Disease
Clinical Variants
Inflammatory bowel
disease
Defining Characteristics
Etiologies
Epidemiology
Crohn's disease
Ulcerative colitis
extraintestinal manifestations?
FTT, erythema nodosum
(extensor surfaces), pyoderma
gangrenosum, monoart/
asymm/ large joint peripheral
arthritis, uveitis, episcleritis,
PSC (more in UC; runs
independent course from IBD),
sacroileitis, ankylosing
spondylitis
bloody diarrhea, tenesmus,
LLQ pain, rectal bleeding,
arthritis/ arthalgias
extraintestinal manifestations?
FTT, erythema nodosum
(extensor surfaces), pyoderma
gangrenosum, monoart/
asymm/ large joint peripheral
arthritis, uveitis, episcleritis,
PSC (more in UC; runs
independent course from IBD),
sacroileitis, ankylosing
spondylitis
Risk factors
Caucasians
Ashkenazi Jews;
SMOKING in
Crohn's disease
NSAIDs
genetic
predisposition
Complications
western world
induction of remission?
Steroids, 5-ASA (reduce
prostaglandins)
intractable disease;
hemorrhage; perforation;
toxic megacolon; colon
extremely severe? Colectomy cancer (correlates w/
duration, extent, severity of
UC)
Maintenance of remission?
5-ASA, 6MP/AZA, biologics
M>F
Diverticulitis
Treatment
Diverticulosis
Lab/Imaging
inflammatory; obstructing;
fistulizing/microperforating
subtypes
Acute appendicitis
Pathogenesis
10-25% of patients w/
diverticulosis
Screening /
Education
Screening /
Education
Screening /
Education
Prognosis determined by
depth of invasion
Prognosis determined by
depth of invasion
aggressive behavior
determined by size and
number of mitoses
Screening /
Education
indications for surgery
(PUD bleeding): massive
hemorrhage leading to
shock; prolonged blood
loss w/ more than 6 units
transfusion; recurrent
bleeding despite
endoscopic tx; recurrent
bleeding during
hospitalization
Screening /
Education
Screening /
Education
IgG antibody
vaccination to protect
against HepA
Screening /
Education
screen all baby
boomers!!
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Ranson criteria for
severity upon
admission: initial
admission- assess
patients age > 55, WBC,
AST, LDH enzymes, &
glucose; within 48h,
assess Ht, Ca++, BUN,
pO2, fluid deficit, base
deficit; if initial and/or
48h labs meet criteria,
can figure out morbidity
& mortality
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Disease
Clinical
Variants
Fanconi's
Syndrome
Secondary
causes of
hypertension
Liddle
syndrome
Congenital
adrenal
hyperplasia
Pseudohypoaldosteronism
Type I
Gitelman
syndrome
Bartter
syndrome
Defining Characteristics
Pathogenesis
(listing)
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Cystinosis (auto
recessive; most
common cause in
childhood)
autosomal dominant
disorder
autosomal recessive
disorder
synthetic aldosterone
infusion
replace K, Mg losses;
restore intravascular
volume w/ salt
autosomal recessive
disorder
autosomal recessive
disorder
Complications
Screening /
Education
Disease
Clinical
Variants
Hyponatremia
Defining Characteristics
seizures (neuro emergency) or
can be gradual onset (intact
neuro exam)
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
electrolyte panel, calculate serum
osmolality
thyroid function tests, med hx, urine
osmolality
Treatment
Complications
Syndrome of
Inappropriate
Anti-Diuresis
(SIAD)
1. normovolemic, mildly
hypervolemic (NEVER
hypovolemic)
2. nl renal, adrenal, and thyroid
functions
3. serum hypotonicity WITHOUT
maximally dilute urine (patients
have inappropriately
concentrated urine)
Hypernatremia
Central
diabetes
insipidus
Nephrogenic
diabetes
insipidus
CNS disorders,
pulmonary disorders,
ectopic ADH
production, meds
(chlorpropamide,
cyclo-phosphamide
IV, carbamezepine)
complete,
partial
Congenital
Acquired complete,
partial
hypertonic saline IV
problem with the production (damage to
idiopathic,
hypothalamus) or secretion of ADH (damage hypothalamus
to posterior pituitary)
trauma, hypoxic
encephalopathy,
posthypophysectomy,
neoplastic
infiltration,
sarcoidosis,
Sheehan's syndrome
not responsive to
exogenous ADH
(because problem with
end-organ!)
Screening /
Education
Disease
Edematous
states
Clinical
Variants
CHF
Defining Characteristics
edema
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
Nephrotic
syndrome
Cirrhosis
ascites
(general)
Congenital
Nephrotic
Syndrome
Membranous
nephropathy
Primary glomerular
disease
95% of cases
in children
related to
systemic disease w/ primary glom
renal manifestations dz (only 60%
(DM, SLE,
of adult
Amyloidosis, drugs - cases)
gold, penicillamine,
Liver realizes that so much protein is being
heroin; infection 40% of adult
lost and ramps up production of lipoproteins; malaria, syphilis,
cases from
increased production accompanied by
hep, HIV;
systemic dz
abnormal transport and decreased
malignancy w/ renal
catabolism leads to hyperlipidemia
carcinoma,
manifestation
lymphoma,
s
melanoma; misc bee sting allergy)
genetics
UA
24h urine protein
albumin blood test, lipid panel
renal biopsy w/ immunofluorescence
most
common in
Finland
onset ages
30-50 y.o.
hepatorenal
syndrome (cirrhosis
= portal HTN =
splanchnic
vasodilation =
stimulation of vasoconstriction in
kidney =
hepatorenal
syndrome)
renal failure
infection (Staph,
pneumococci; loss
of proteins like Ig,
complement)
resistant to most
treatments; severe cases
require bilateral
nephrectomies and
subsequent lifelong
dialysis
death secondary to
sepsis
other complications hyper-coagulopathy,
infection, stroke
Screening /
Education
Disease
Clinical
Variants
Minimal
change
disease
Defining Characteristics
normal biopsy findings EXCEPT
diffuse foot process effacement
Pathogenesis
Etiologies
most
common
nephrotic
syndrome in
kids
primary /idiopathic
Acute poststreptococcal
GN (postinfectious GN)
Lab/Imaging
Creatinine: nl (nl GFR)
Treatment
similar to EASS
Complications
LM: nl glomerulus
IF: none
EM: diffuse foot process effacement
(fusion)
50% have renal
failure in 10y
20% rapidly
progress to ESRD in
2y
recurrence in 2550% of transplants
IF: none
EM: diffuse foot process effacement
+ focal/segmental sclerosis of
glomerulus
Membranoproliferative
GN Type I
(MPGN1)
Risk factors
Nephritic
presentation
Epi
few spont
remissions
slowly progressive
but unremitting (50%
develop chron renal
failure in 10 y)
Screening /
Education
Disease
Clinical
Variants
Membranoproliferative
GN Type II
(MPGN2)
Defining Characteristics
looks similar to Type I under LM
dense deposit disease linearized bands of C3
deposits
a/w partial lipodystrophy
hypocomplementemia for C3
only!!
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
Screening /
Education
atherosclerosis
(AAA, MI, PVD);
amputation; HTN;
CVA, stroke;
retinopathy,
peripheral
neuropathy,
infection,
nephropathy
year 2: kidney
enlarges,
increased GFR
Crescentic GN
(Anti-GBM,
Goodpasture's
dz)
Anti- GBM dz: limited to kidneys, in-situ antibody formation to fixed antigen in
rapidly progressive GN (RPGN) non-collagenous domain of Collagen type IV
in GBM
w/ nephritic presentation and
ARF
ruptured GBM from antibodies attacking antiNC1 domain causes destruction of collagen
Goodpasture's: involves
type IV and release of fibrin, stimulating the
kidneys & lungs (pulmonaryproliferation of parietal epithelial cells and
renal syndrome - ARDs +
formation of cellular crescents
RPGN)
Diabetes
mellitus diabetic
nephropathy
Systemic lupus
erythematous lupus
nephritis
25.8 million
children and
adults in the
U.S.
renal
involvement
30-90% of
SLE patients
leading cause of
kidney failure
papillary necrosis
(acute
pyelonephritis seen
more in DM but also
PN w/ obst and
NSAID abuse)
year 5: GFR
drops and
plateaus
year 15-25:
steady decline in
GFR (leading to
massive
proteinuria)
Disease
Clinical
Variants
Microscopic
polyangitis
Defining Characteristics
P-ANCA vasculitis
palpable purpura - skin, mucus
membranes, lungs, brain, heart,
GI, kidneys, nerves, muscle
clinical features depend on
involved organ system:
hemoptysis, arthalgia, abd pain,
hematuria/ proteinuria,
hemorrhage, muscle pain/
weakness
Pathogenesis
systemic necrotizing vasculitis of small
vessels (arterioles, venules, capillaries)
autoantibodies against myeloperoxidase
Pauci-immune mechanism: presumed
immune mech but no IF or EM evidence of
immune complex deposition in organs
Etiologies
Epi
precipitating immune
reaction (PCN,
microbes- Strep,
heterologous
proteins, tumor
antigens)
Risk factors
Lab/Imaging
Treatment
Complications
kidneys: leukocytoclastic
vasculitis and acute
necrotizing (and often
crescentic) GN
Wegener's
Classic triad (acute necrotizing
granulomatosis granulomas of ENT, lungs hemoptysis; necrotizing
vasculitis of small & med
vessels; acute
necrotizing/crescentic GN)
M>F
C-ANCA
mimics TB -necrotizing
granulomas, cavitary lesions
Henochdeposition of polymeric IgA1 within arterioles unknown
palpable cutaneous purpura
Schonlein
(usually on lower half of body); causes leukocytoclastic vasculitis and
activation of alternative complement pathway
Purpura (HSP) - arthritis, acute abd pain (+/HSP nephritis bloody diarrhea), HSP nephritis
(IgA nephropathy; hematuria +
proteinuria)
children &
young adults
Plasma cell
myeloma
(multiple
myeloma) light chain
cast
nephropathy
50-60 y.o.
generally poor
prognosis
Screening /
Education
Disease
Clinical
Variants
Glomeruloneph Experimental
ritis
acute serum
sickness
(similar to
human poststreptococcal
GN)
Heymann
nephritis
(idiopathic
membranous
nephropathy in
humans)
Hyperkalemia
Defining Characteristics
single injection of Ag (acute
antigenemia)
stereotypical course
self-limited, short duration
Pathogenesis
Etiologies
Epi
IgA
asymptomatic & persistent
Nephropathy
hematuria (gross or micro), +/(IgAN, Berger's proteinuria; mesangiopathic dz
disease)
usually manifests as slow
insidious progression towards
ESRD
Complications
Screening /
Education
Treatment
Masugi
in situ formation of immune
Nephritis (Anti- complexes
GBM disease)
Anti-GBM dz does occur in
humans, but target Ag = NC1 of
collagen type IV
Lab/Imaging
biopsy: diffuse proliferative GN
(>50% of glomeruli have lesions),
heavy mononuclear infiltrate,
endothelial cell swelling,
subepithelial humps
Risk factors
most
common GN
in developing
world
(Western
Pacific rim)
crush injuries
no effective tx
1. stabilize cardiac
membrane (esp if serious
EKG changes) - give
calcium (Ca gluconate by
periph IV)
2. redistribute K+ by
giving insulin (causes K+
to go back into cells) or
B2 agonists
3. remove K+ by giving
kayexalate/sorbitol (bind
K+, causing diarrhea) or
hemodialysis
Ca IV is
avoid potassium
contraindicated if pt in diet for 6
on digoxin!!
months
(artichokes,
Do not mix Ca IV w/ avocados, tomato
NaHCO3 solutions paste, OJ,
(causes precipitation potatoes, milk,
of CaCO3)
bananas, steak,
hamburger, etc)
Disease
Clinical
Variants
Hypokalemia
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
Chronic Kidney
Disease (CKD)
Diabetes,
HTN
CVD = leading
cause of death
decreased life
expectancy
Renal
hypoplasia
unilateral - no problems
very rare
diminutive kidney
Screening /
Education
Staging:
1. kidney damage
w/ nl or inc GFR
(>90)
2. mild dec GFR
(60-89) + kidney
damage
3. moderate dec
GFR (30-59)
4. severe dec
GFR (15-29)
5. Kidney failure
(GFR<15)
Disease
Clinical
Variants
Renal ectopia
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
increased risk of UTI
from stasis
simple - pelvic,
subdiaphragmatic, thoracic
increased risk of
injury
sporadic
1/400-600
slight risk of
infections, kidney
stones, and renal
pelvis tumors
Type I (DT)
Hereditary (auto
recessive mutation
in Cl/HCO3exchanger),
interstitial nephritis
(lead/lithium/
analgesic abuse;
autoimmune Sjogren's, RA, SLE,
PBC, thyroiditis;
nephrocalcinosis;
drugs - amphotericin
B, toluene)
Childhood
hereditary dz
(cystinosis,
tyrosinemia, GSD,
Wilson's, Lowe's,
variable urine pH (diet dep),
galactosemia),
serum bicarb 14-20, normal/low
carbonic anhydrase
K+
inhibitors
(acetozolamide,
topiramate),
interstitial nephritis
(rare), renal
transplant rejection
(very rare),
amyloidosis, multiple
myeloma
normal anion gap acidosis;
low renin, hypoaldosteronism, or aldosterone drugs (ACEI, AngII
moderate renal failure (GFR 20- resistance prevents the secretion of K+
inhibitors,
50), impaired NH4+ and
(hyperkalemia), indirectly causing charge
aldosterone
phosphate excretion
exchange during which causes H+ to enter
antagonists)
the cells [low aldosterone prevents K+
maximally acidic urine (pH <
secretion; hi K+ blocks ammonium
5.3), mild acidosis (HCO3production, so H+ in urine is not bound to
>15), hyperkalemia
ammonia --> maximally acidic urine]
Type 2 (PT)
Type 4
increased risk of
Wilms tumor
(isthmus)
Screening /
Education
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Type B LA
Diabetic KA
Alcoholic KA
Ketoacidosis
Metabolic
alkalosis
Benign renal
neoplasms
Papillary
(cortical)
adenoma
Angiomyolipoma
Oncocytoma
Complications
chloride sensitive
metabolic alkalosis
from bicarb
load/drag (calcium
alkali syndrome) or
Generation: vomiting, NG suction,
decreased EABV
increased distal Na+ delivery in volume
(vomiting, increased
depleted states (loop/ thiazide diuretics,
nonreabsorb anions), respiratory comp (post Na+ deliverychronic hypercapnia), alkali consumption/ diuretics, postadmin; mineralocorticoid excess, MC excess hypercapnic state,
hypercalcemia)
syndromes (Bartters, pseudo-hyperald)
Maintenance: low EABV (chloride deficiency activates RAAS preventing base secretion &
increasing HCO3 reabs secondary to Na+;
insuff Cl- to exchange w/ HCO3 in distal
nephron), pathologic mineralocorticoid
excess, severe hypokalemia
Treatment
chloride supplementation
reverses the alkalosis (if
chloride sensitive)
chloride resistant
metabolic alkalosis
(hi renin: renal artery
stenosis, malignant
HTN; low renin:
primary
aldosteronism,
Cushing's syndrome,
Liddle syndrome)
common;
incidence
increased w/
age
<1% of renal
tumors
usually in
adults
4-7% of adult
renal
epithelial
tumors
spont retroperitoneal
hemorrhage (pts
present w/ severe
back pain)
Screening /
Education
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
Conventional
(clear cell)
RCC
Epi
Urothelilal
arises from renal pelvis (collecting system hematuria
carcinoma
urothelium)
(transitional
40-50% of cases have cocell carcinoma) existing bladder urothelial tumors
most common tumor of renal
collecting system and ureter
partial nephrectomy
(nephron sparing
surgery)
metastases
(LUNGS, lymph
nodes, liver, bone,
adrenals,
contralateral kidney,
brain, heart, spleen,
intestine, skin)
smoking,
obesity in
women,
HTN, VHL
disease
(develop
RCC in 50%
of cases),
hereditary
RCC w/o
VHL,
tuberous
sclerosis
Hereditary
papillary renal
cell cancer
Hereditary
leiomyomatosis
RCC
radical nephrectomy
cryoablation (small
tumor, poor surgical
candidates)
males 3:1
increased risk for papillary type 2 FH gene codes for fumerase hydratase
RCC
enzyme;
10-20% of
adults RCCs
horseshoe
kidney
von Hippel
Lindau (VHL)
syndrome
Screening /
Education
65,000
cases, 13500
deaths in
U.S.
cyclophosph
amide
Inherited
disorders of
RCC
Complications
M>F
hereditary papillary
carcinoma (VERY
rare)
Treatment
hereditary? CT imaging
to monitor dz
progression; nephron
sparing surgery, radical
nephrectomy,
cryotherapy (if not
surgery candidate);
screen family members
usually > 50
y.o.
Lab/Imaging
Rising
incidence
Papillary renal
cell carcinoma
Risk factors
10-16% risk
RCC
Fuhrman nuclear
grading system
(Grade IV - bad!!)
- prognostic
combined w/
staging (see
above)
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
Familial Renal
Oncocytoma
Lynch
Syndrome
Wilms' tumor
(nephroblastom
a)
nephrectomy and/or
chemotherapy
1/8K-10K
Tuberous
sclerosis
no gender
preference
if see angiomyoplipomas on
kidneys - think tuberous
sclerosis!
Bladder
exstrophy
infection
ulceration
adeno-carcinoma
squamous cell
carcinoma
Acute cystitis
older men
younger
women of
reproductive
age
immunosupp
non-infectious:
chemo, radiation,
trauma
death - esp if no
access to HC
(developing world)
pyelonephritis!!!
Screening /
Education
Disease
Clinical
Variants
Schistosomiasi
s
Defining Characteristics
world's leading cause of
hematuria and bladder cancer
Pathogenesis
ova are deposited in veins of muscularis
propria, leading to degeneration and
inflammation
early changes - necrosis, eosinophils w/
mucosal ulceration
Etiologies
Schistosoma
hematobium common in Egypt
(water borne
parasite; lodges in
pelvic veins around
bladder)
Epi
Risk factors
Africa &
Middle East
Lab/Imaging
Treatment
squamous cell
carcinoma
irritative voiding symptoms, gross destruction of overlying vessels in bladder --> cyclohematuria (Med emergency!!)
excessive bleeding
phosphamide,
radiation
HSV, CMV,
adenovirus
benign course once injury source chronically inflamed bladder w/ grossly noted bladder
removed
polypoid lesions w/ edema or papillary
catheterization,
lesions
fistulous tracts
benign lesions occuring most
defects in phagocytic or degradative
E. coli
commonly in bladder but also
functions of histiocytes in response to GN
Proteus
ureters, urethra, renal pelvis, etc. bacteria
Polypoid
cystitis
Malakoplakia
Cystitis cystica
et glandularis
Squamous
metaplasia of
bladder
Urothelial
carcinoma in
situ (CIS)
malignant
Urothelial
papilloma
schistosoma
infection (globally)
immunocomp,
women
long standing in
dwelling catheters
(US)
Normal urothelium --> dysplasia
painless hematuria
smoking, chronic
(preneoplastic atypia - transformation to abnl cystitis (SCC),
appearing nucleus) --> carcinoma (CIS flat
chemical exposure,
urothelial carcinomas are the
most common bladder cancers lesions OR noninvasive papillary lesions) --> cyclophosphamide,
invasion
radiation
(>90%)
Screening /
Education
hydroureter,
hydronephrosis,
bladder ulcers,
bacterial infections,
renal failure
Complications
remote risk of
adenocarcinoma
histology: hyperkeratosis
most
common
urinary tract
cancer
smoking
histology: dysplasia - enlarged
arylamines urothelium
(dyes)
Schistosoma
hematobium
4th most
(70% cases
common
are SCC)
cause of
Phenacetin
cancer death use
in males
long term
cyclophosph
M>F
amide use
histology: cells at least 5x size of
stromal lymphocytes, enlarged/
hyperchromatic nuclei, discohesion
(shedding), prominence of vessels,
high N/C ratio (CIS cells have very
little cytoplasm), pagetoid cells
(malignant cells interspersed w/
benign cells)
urine cytology - can sometimes show
CIS if discohesive
visible on cytoscopy (but need histo
to tell if malignant or benign lesion)
histology: finger like projections w/
presence of umbrella cells and
abundant cytoplasm (low N/C ratio)
bleeding,
obstruction,
metastasis
staging:
pTa & pTis = noninvasive (>95%
5y survival); T1T4 based on
depth of tumor
invasion
Disease
Clinical
Variants
Low grade
papillary
urothelial
carcinoma
High grade
papillary
urothelial
carcinoma
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
malignant
Treatment
Complications
non-invasive usually
orderly arrangement w/ minimal
variation in polarity; minimal
atypia (scattered enlarged
hyperchromatic nuclei), few
mitotic figures
malignant
usually invasive
overall disorderly arrangement w/
irregular clusters of cells & fused
papillae; marked atypia (similar
to CIS), numerous mitotic figures;
discohesive single cells
Lab/Imaging
long term
catheterization
Schistosoma
hematobium
bladder exstrophy
5% of
bladder
tumors in
US; 75% of
bladder
tumors in
Egypt, Sudan
smoking,
Schisto
infection,
chronic
catheter
placement
smoking
Renal
obstruction
Adenocarcinoma
malignant
glands + mucin
Small cell
carcinoma
malignant
Unilateral
bilateral
UPJ
chronic - silent
fluid overload, weight gain,
less pain than unilateral
obstruction
occasionally, acute symptoms
hydronephrosis
renal distention increases
susceptibility to trauma
Nephrolithiasis
may spontaneously
resolve in infants
urinary stasis,
decreased renal
function (reversibility
related inversely to
amount of time
obstructed), HTN,
postobst diuresis,
electrolyte abnl
genetic
predisposition,
dehydration
urinary
stasis,
dehydration,
infection,
metabolic
states
(hypercalciuria,
hypocitraturia,
hyperoxaluria,
hyperuricosuria)
immobilized,
RTA,
sarcoidosis,
hyper-PTH,
short bowel
syndrome
removal of stone,
increased fluid intake
Screening /
Education
Disease
Kidney
infections
Clinical
Variants
Pyelonephritis
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
women w/
Microscopy: WBC casts
FH or PMH
of recurrent CT Imaging if persistent sx despite tx
UTIs; men
(R/O complications)
w/ GU abnl;
diabetics;
elderly
Treatment
Complications
infection + obstruction
(secondary to stagnant pus
building up in the collecting
system)
Emphysematou EMERGENCY - requires acute
air filled pockets within kidney parenchyma
s
drainage
due to infiltration of gas-forming bacteria
pyelonephritis
severe necrotizing infection due
to anaerobic, gas forming
uropathogens
Abscess
Perinephric - occurs secondary
to obstruction of inf kidney; E.coli
or Proteus
Others
Urinary
retention
Urinary
incontinence
(general)
diabetes
urgent nephrectomy
neurologic issues;
certain drugs;
prostate
enlargement;
urethral stricture;
trauma (urethral
disruption)
Urge
Overflow
Total
coughing, laughing,
sneezing, valsalva
bladder infection
diabetes
developing
countries
FEMALES
Vesicoureteral
reflux
Urethral
stricture
Urethral cancer
genetics
only urologic
cancer more
common in
females; very
rare!
obstruction
Screening /
Education
Disease
Clinical
Variants
Benign
prostatic
hypertrophy/
hyperplasia
(BPH)
Defining Characteristics
occurs most commonly in
transition zone
obstructive sx (prostatism)hesistancy, weak stream,
dribbling, straining to pass
urine, prolonged micturition
(urination), feeling of
incomplete bladder emptying
(interruption of primary
stream), urinary retention
irritative sx - (less specific for
BPH) urgency, frequency,
nocturia, urge incontinence
(make sure you R/O cancer!!)
Pathogenesis
Etiologies
presence of
androgens (DHT testosterone
converted to DHT by
stromal cells via 5a
reductase)
Epi
Risk factors
age
Lab/Imaging
prostate exam
cystoscopy for bladder diverticulum
BPH
highest
incidence of
all US male
cancers
(outside of
skin Ca)
age, FH,
race (African
Americans),
diet
(lycopene
maybe
protective)
2nd leading
cause of
cancer
deaths in
men
Scrotal
swellings
hydrocele
testicular torsion
(dead testis from
lack of bloodflow)
10-15% of
men; 10% of
these are
bilateral
unilateral right
varicocele
concerning bc
probably due to
pressure on the
vena cava directly
from kidney tumor or
retroperitoneal mass
Screening /
Education
uncontrolled BPH
meds (a-adrenergic
can cause infection,
blockers- open the ext
urethral sphincter &
cancer, stones
histology: hyperplasia of stroma (fibro- relaxes smooth muscle,
muscular) & glands
5a-reductase inhibitors - catheterization if
decrease DHT to shrink urinary retention
prostate; anticholinergics - relax the
bladder to prevent
uregency; combo tx)
Complications
Prostate cancer
Treatment
peak
incidence in
males aged
15-34
undescended
testes
genetics
HIV
atrophy
FH?
Trauma?
removal of
retroperitoneal LNs (both
sides since L to R
spread) - interaorto-caval
LNs, retrocaval LNs, right
paracaval LNs
chemo
removal of testis
Disease
Clinical
Variants
Male infertility
Defining Characteristics
Pathogenesis
Epididymitis
Erectile
dysfunction
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
Screening /
Education
varicoceles most
common factor
any age
Flouroquinolones (Cipro)
exercise in earlier
ages prevents
ED
Penile cancer
10% of men
by age of 5060
rare
(however,
1% of
cancers in
Africa are
penile)
women @
higer risk
(shorter
urethra,
sexual
activity,
pregnancy);
males most
common as
infants
(suggests
GU abnl)
(general)
Symptomatic
bacteriuria/
uncomplicated
UTI
loss of nl bacterial
flora (Abs),
environment of
bladder, disruptions
in urine flow
(obstruction,
vesicoureteral
reflux), foreign
bodies
mostly
Caucasians
but other
races too
elderly (inc
bactereriuria,
Estrogen,
prostatic
secretions;
comorbid
conditions)
genetics (P
group Ag on
RBCs &
uroepith
cells)
Gram stain - hi sens & spec but rarely correct underlying risk
done unless requested
factors
urine cx - atyp present, early sx of
recurrence after tx, clinical susp for
pyelonephritis, recurrent infxn prev
treated w/ Abs
pregnancy? 7d w/
amoxicillin/ oral
cephalosporin,
nitrofurantoin, or TMPSMX; avoid
flouroquinolones!!
lower threshold for
hospitalization
D/C indwelling devices
ASAP
void after
intercourse;
cranberry juice/
supp to reduce
sx; intravag
estradiol in
postmenop
women; correct
underlying
structural abnl;
Ab prophylaxis
(LAST RESORT)
Disease
Clinical
Variants
Complicated
UTIs (e.g.
catheterassociated
UTIs)
Defining Characteristics
patients who need longer course
of therapy, interventional
procedures, have pathogens w/
Ab resistance, or secondary
complications
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
remove underlying
mechanism (catheter,
obstruction)
Complications
Screening /
Education
indwelling devices
can become havens
for biofilms;
encrusted
1. insert
catheters only for
appropriate
indications
2. remove ASAP
3. properly train
those who
insert/maintain
4. aseptic
technique
5. maintain
closed drainage
system
6. maintain
unobst urine flow
7. hand hygiene
minimize unneccessary
tx (asymp bacteriuria)
Limit Ab use unless
underlying process is
resolved!
Avoid routinely changing
catheter bags,
antibmicrobial
prophylaxis, bladder
irrigation, antiseptic
solutions in drainage
bags, routine screening
for asympt bacteriuria
GU
tuberculosis
Asymptomatic
bacteriuria
15% of
homeless
extrapulm TB
disease
catheters
may respond to TB
therapy but usually
requires surgery bc very
extensive dz by time dx
otherwise, remove
catheters if source (and
no longer needed)
Cystitis
if local TMP-SMX
resistance <20%: TMPSMX DS BID x3d
frequency, urgency,
suprapubic pain, dysuria,
gross hematuria
Vaginitis,
urethritis
Prostatitis
sexual
mandatory pelvic exam for vag d/c
or lesions (Chlamydia/ gonorrhea,
history of
HSV, trichomonas, BV)
new
partners or
hi risk
sexual
practice
unclear mechanism - possibly due to urethral GN enteric
reflux or post-GU instrumentation
organisms (E.coli)
very small
proportion of
prostate
cases
initial therapy: IV Ab
(fluoroquinolones)
later therapy: oral Ab
Ureaplasma,
Chlamydia
R/O complications if
unresponsive
prostate massage: less inflammation treat based on culture
but positive culture
results
semen culture if prostate massage
uncomfortable
fluoroquinolones,
sometimes doxycycline
or macrolides
Prostate abscess
Disease
Clinical
Variants
Chronic pelvic
pain, no
detectable
inflamm
(Type III)
Asymptomatic
inflamm
(Type IV)
Autosomal
dominant
polycystic
kidney disease
(ADPKD)
Defining Characteristics
Etiologies
Epi
Treatment
Complications
ESRD
HTN, gross
hematuria, pain,
nephrolithiasis, UTI long before dec
GFR!
hemorrhage of cysts
- acute onset of pain
localized to kidney
comp of polycystic
liver dz (ascites,
portal hypertension,
varices, hepatic
venous obst, liver
cyst infection)
Lab/Imaging
M=F
(general)
Risk factors
Pathogenesis
CT for complications
Screening /
Education
Disease
Clinical
Variants
Intrinsic Renal
Failure
Defining Characteristics
Pathogenesis
Postrenal
failure
Etiologies
ATN - ischemic
causes,
nephrotoxins (Abs,
contrast dyes, heavy
metals, chemo
agents; myoglobin,
Hg, calcium
phosphate stones,
uric acid)
Epi
Risk factors
Lab/Imaging
path: muddy brown casts - ATN;
eosin infiltrate + edema between
tubules - AIN
BUN/Cr ratio 10-15:1; Uosm <350;
Una >40; FENA >2; FEurea >50
AIN - drugs
(NSAIDs, Abs,
diuretics, others);
Infxn (PN), immuno
(SLE, rejection), infilt
(sarcoid, leuk,
lymphoma)
UUT nephrolithiasis,
blood clot,
retroperitoneal
fibrosis, malignancy
LUT - stricture, BPH,
prostate Ca
Neurogenic - DM,
anticholinergics,
neurologic d/o
Treatment
Complications
Screening /
Education
Disease
Diabetes
mellitus
Clinical
Variants
(general)
Type 1 DM
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
excessive urination,
excessive thirst, fatigue,
weight loss
progressive autoimmune
destruction of B-cells --> insulin
deficiency (causing the
opposite of insulin - rather than
storing energy, the body tries to
make glucose & breaks down
glycogen, fats, & protein)
pancreas: inc
glucagon, dec
insulin
secretion
fat: dec
glucose
nutrients pass into the urine
uptake, inc
(weight loss, polyphagia);
FFA output
dehydration bc body H2O is
muscle: dec
used to eliminate extracell
glucose uptake
glucose in the urine
liver: inc
hepatic
dec intracell glucose = dec
glucose output
energy; body attempts to inc
gut: slowed
chronic hyperglycemia: 3Ps intracell glucose and dec
gastric motility,
+ severe cachexia (unable extracell glucose (osmotic
inc glucose
diuresis); as unable to use
to drive glucose intracell)
uptake
glucose, body attempts to
brain: dec
increase energy by using fats = satiety, ANS
ketones = acid = DKA
reg
Lab/Imaging
Treatment
Diabetic ketoacidosis,
hypoglycemia, see
chronic complications
below
subcutaneous insulin
DKA
therapy that mimics
physiologic insulin
(continuous insulin - pump
or basal injection w/ bolus
injection at meals)
Whites
colder climate
metabolic syndrome:
waist circum > 32"F or
38"M + any 2 factors (HTN,
low HDL <40M or <50F,
hyperlipidemia >150,
impaired FBS >100) - a/w
underlying insulin
resistance inc risk of CVD
& DM
insulin action impaired but
does not get much worse
btwn pre-diabetes to DM;
insulin secretion dec
significantly w/ impaired
glucose tolerance,
suggesting dual defects in
T2DM
DKA, inc FBS, inc
postprand gluc
polygenic muts
in TCF7-L2
(dec insulin
secretion) +
dec insulin
action (resist
via inactivity +
obesity)
24 million
diabetics in
U.S. in 2012
strong FH,
minority groups,
overweight, no
physical activity,
prevalence is pregnancy
highest in
older people Diet: more trans
(60+) but
fat, more sat fat,
highest
higher glycemic
inc IHL a/w dec incidence in load (less fruits,
insulin action; middle aged veggies, more
fat)
inc oxid stress (40-59)
a/w inc B-cell
Native
apop, dec
Americans>
insulin syn &
blacks>
secret
hispanics >>
dec insulin, inc Asians>
glucagon post whites
prandial (opp
of nl)
Complications
Disease
Clinical
Variants
Gestational
diabetes
Defining Characteristics
Chronic
complications
of DM
Etiologies
Diabetic
Ketoacidosis
(DKA)
Pathogenesis
Retinopathy microvascular
Nephromicrovascular
pathy
Neuropathy microvascular
CAD,
macrovascular
ischemic
heart dz
7% of all
pregnancies
complicated
by GD
1/3 of GDM
patients will
have DM
postpartum
increased gluconeogenesis
causes hyperglycemia
increased lipolysis = release of
FFA, inc B-oxidation of FFA =
inc acetyl CoA which is
converted to ketone bodies in
the liver
Epi
Risk factors
Lab/Imaging
FH of DM
h/o macrosomia
obesity
AMA (>35y.o.)
h/o poor
obstetric
outcome
h/o GD
ethnicity (AA,
hispanic, NA, PI)
50% of GDM
patients will
develop DM
within 10y of
affected
pregnancy
medical illness,
stress, or
omission of
insulin
T1DM
Treatment
A1: 30kcal/kg/day diet
BMI>30: 30% caloric
restriction
nutritional counseling. Ex
during pregnancy,
maintain FBS < 95 & 2h
postprandial <120
A2s: lifestyle mods +
glyburide (low doses 2.5
mg --> 10 mg); if still not
controlled, add insulin
(does not cross placenta)
OCP postpartum,
preconceptual glycemic
control imperative (diet,
ex, behavioral mods to
avoid GDM recurrence)
Complications
frequently resolves
after delivery
Maternal comps - HTN
d/o (pre-eclampsia,
eclampsia); C/S;
stillbirth; trauma
fetal comps macrosomia,
hyperbilirubinemia,
operative delivery,
shoulder dystocia,
birth trauma, neonatal
hypoglycemia, resp
distress syndrome,
childhood obesity
metabolic acidosis
hyperglycemia (usually >
300)
ketosis
pseudo-hyponatremia
(dilutional), hyperkalemia
pre-renal azotemia
Hypoglycemia
(general)
neurological
compromise or mental
retardation
Disease
Clinical
Defining Characteristics
Pathogenesis
Variants
Ketotic hypo- Ketones in urine or serum substrate limited: unavailable
glycemia
carbs/ poor storage = unable to
fast for a long time w/o
becoming ketotic (MSUD)
Hormone deficiency: panhyopopituitarism (GH, ACTH def),
glucagon def, epi def, cortisol
def (Addison's, congenital
adrenal hyperplasia)
Others: drug-induced, systemic
d/o (can't meet body's energy
demands), liver disorders (can't
make or use glucose - hepatitis,
cirrhosis)
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
Substratelimited
Hormone
deficiencies
GSDs
D/Os of gluconeogenesis
Drugs alcohol,
salicylates,
quinine,
valproic acid,
insulin
Medium Chain
Acyl
Dehydrogenas
e Deficiency
(MCADD)
HyperCongenital
insulinism
1/15,000
glucokinase
also called nesidioblastosis, GOF muts (activated by leucine) mutation (AD)
B-cell hyperplasia, B-cell
of glutamate dehydrogenase =
dysmaturation syndrome
inc oxid of glutamate = inc aketoglutarate, ATP, & insulin
glucokinase mut decreased glucose
GOF muts of glucokinase
threshold for insulin to
(glucose sensor, 1st step in
glycogen synthesis & glycolysis)
shut down
= activation of insulin until BG is
GDH mut - inc NH3 levels around 40
Disease
Clinical
Variants
Acquired
Defining Characteristics
Whipples triad suggests
insulinoma
(hypoglycemia +
symptoms - weakness,
tremors, sweating, hunger,
palpitations, weight gain,
exercise induced, CNS sx,
psychiatric probs, relief w/
glucose)
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
glucose tablets, IV
glucose, or glucagon (if
seizing or unconscious)
reactive hypoglycemia
can be a precursor to
T2DM
Levothyroxine
(Synthroid, 1.6ug/kg
body weight)- pure T4;
DOC for replacement/
suppression, keep TSH
WNL, watch free T4 w/
sec/ tert hypothyroidism
diabetes,
atherosclerosis,
reactive hypoglycemia =
ingestion of simple sugars w/o
fats or carbs = insulin spike that
easily takes up simple sugars
Hypothyroidism (general)
Congenital
Hashimotos
thyroiditis,
subacute
thyroiditis, diet
reduced metabolic state,
primary: thyroid gland is
iodine def,
dec CO, lethargy, dec
affected
appetite w/ inc weight
secondary: pituitary is affected lithium OD
gain, coarse hair, mental (TSH deficiency, pituitary tumor) (rare),congenit
al errors of TH
slowness, dry skin, slow tertiary: hypothalamus is
pulse (brachycardia),
affected (tumors, infiltrative dz) release/
synthesis
cool/dry/ puffy skin, droopy
(rare),
eyelids, large tongue, +/most common causes?
goiter, thinning of lateral 1/3 Autoimmune dz, radioiodine radiation
exposure,
of eyebrows, constipation, or thyroidectomy, pituitary
iatrogenic
cold intolerance,
insufficiency
(radioactive
iodine tx or
KIDS: same sx as adults
surgery
BUT poor linear growth,
ablation),
excess weight gain, &
postpartum
poor school performance
thyroiditis
underproduction of
T3&T4
Failure to thrive!
iodine def =
elderly
most common
cause globally
of hypothyroidism
F>M,
increased
prevalence w/
age
goiter.
Subclinical
postpartum
Painless thyroid
10% of elderly
slow titration of
Levothyroxin in elderly
to avoid complications
w/ coronary heart
disease
thyroid gland
dysgenesis or
agenesis
impaired development of
CNS & skeleton, severe
mental retardation, short
dyshormogenesis - deficiency or lingual thyroid
stature, coarse facial
absence of TPO
features, protruding tongue
& umbilical, +/- goiter if
dyshormogenesis
thyroid hormone
(Levothyroxine)
increases growth &
mental development - if
unsure, treat shortly after
birth bc brain growth 8085% complete by 3y.o.
treat moms if maternal
thyroid deficiency
2nd most
common
cause of
hypoT AFTER
iatrogenic!
CRETINISM = mental
retardation if not
treated early!!!
Signs?? Impaired
skeletal/CNS
development)
risk of bleeding if
removal of lingual
thyroid
Disease
Hyperthyroidism
Clinical
Variants
(general)
Defining Characteristics
overproduction of T3&T4
inc metabolic state,
nervousness, insomnia,
fatigue, irregular heart beat
(afib), tachycardia, inc
appetite w/ dramatic weight
loss, heat intolerance,
exopthalmos, +/- goiter,
hyperhidrosis, alopecia,
hyperdefecation, abnl LFTs,
osteopenia, hi Ca, tremors,
proximal myopathy,
periodic paralysis,
onycholysis (separation of
fingernail)
Pathogenesis
Etiologies
Epi
Risk factors
exaggerated T3 and T4
production causes suppressed
TSH (negative feedback)
85% of the
Graves dz
cases caused
(young F) by Graves
see below
toxic,
5-10% of pts will have nl T4 but multinodular
exaggerated T3 (T3 toxicosis)
goiter
(elderly) - see
pituitary tumors can sometimes below
cause inc T3, T4, AND TSH!
TH overdose
(most
common
cause!)
thyroid tumor,
subacute
thyroiditis,
postpartum
thyroiditis,
painless
thyroiditis
Lab/Imaging
Treatment
Complications
osteoporosis, bone fx
amiodarone
Graves
disease
Toxic
adenoma
Thyroid storm
(Thyrotoxicosis)
Thyroglossal
duct cyst
Lateral aberrant
thyroid
lateral to
sternocleidomastoid
F>M (7:1)
2% US
women
FH
hi T4, T3; undetectable TSH, "cool down" with antithyroid drugs; 50% of pts
positive TSI (thyroid
will be cured w/ meds
stimulated IgG), goiter
alone
possible T3 toxicosis (inc in
med tx: propanolol
T3 only)
(tachycardia, inhibits
Hot, diffuse nodule on I-123 conversion of T4 to T3),
anti-thyroid meds
scan
(methimazole, PTU for
pregnant women ONLY),
GCs (inhibit T4-->T3)
usually require
radioactive iodine
surgery also option
2% of
hyperthyroid
cases
tachycardia, fibrillation,
shock, heart failure
Propanolol +
thioureylenes + large
doses of Lugol's
histology: variable
epithelium cyst lining (nondescript cuboidal,
sometimes squamous)
histology: lymphoid tissue
+ thyroid glands
blindness and
decreased ocular
vision if exophthalmos
not treated!
Radioactive iodine -->
hypothyroidism
Disease
Goiter
Clinical
Variants
(general)
Defining Characteristics
enlargement of the
thyroid gland
Pathogenesis
in low iodine areas, TH cannot
be produced so hypothalamus
increases TSH secretion =
increased growth of thyroid
gland
Etiologies
Epi
endemic
(iodine
deficiency,
goitrogens!),
sporadic,
familial
Risk factors
Lab/Imaging
endemic areas
(Alps, Andes,
Himalayas;
iodine def = TSH
= hyperplasia)
FH of Graves
euthyroid - nontoxic
Treatment
Complications
diffuse, symmetrical
enlargement
Toxic (Graves disease)
Non-toxic (simple)
F>M
hyperthyroid - Graves
Multinodular
nodular, lumpy
enlargement
older age
carcinoma,
benign
hyperplasia
palpable
nodules in 6%
women, 2%
men
usually euthyroid
require fine needle
aspiration cytology to define
hyperplasia OR malignant
epithelium
I-123 scan: nl thyroid nod will
have diffuse filling/uptake;
"cold" nodules (no iodine
uptake - VERY concerning
for Ca)
gross: if uniform tan/ gooey
material w/o capsule - colloid
nodule; capsule w/ complete
integrity - adenoma; thick
capsules - malignancy
histology: uniform w/o
transcapsular invasion
(adenoma)
hypothyroidism if tx w/
anti-thyroid meds
prevent sx BUT DO NOT radioactive iodine
(although less
CURE DZ!!
common than Graves
patients)
Radioactive iodine +/surgery (only if trouble
swallowing, compression
of trachea) - surgery can
sometimes be better
option if VERY large
Disease
Thyroiditis
Clinical
Variants
Thyroid
carcinoma
Defining Characteristics
papillary - sporadic, PMH of
neck radiation; slow
growing, good prognosis
follicular - more aggressive
but good prognosis;
common in iodine def
countries
medullary - arise from Ccells (parafollicular cells
secrete calcitonin),
neuroendocrine neoplasm
(MEN IIa, MEN IIb, nonMEN) w/ amyloid deposition
undifferentiated - no
follicular/ papillary morph,
elderly, rapid growth, local
invasion, poor prognosis
Malignant lymphomaelderly women, a/w
Hashimotos thyroiditis
Acute
Chronic
Subacute
Fibrous
Hashimoto's thyroiditis
Pathogenesis
normal follicular cells -->
adenomas under influence of
RAS oncogenes --> subset of
adenomas progress into
follicular carcinomas
normal follicular cells -->
papillary carcinomas under
influence of RET mutations
pre-existing follicular or papillary
cancer acquires p53 mutation
to become anaplastic
carcinomas (hi grade!!)
Riedel's thyroiditis
woody/ stone hard
thyroid gland
Etiologies
Epi
Risk factors
uncommon
radiation to neck
but increased
incidence w/I genetic
past 20 years, (medullary)
F>M
pre-existing
young- mid
thyroid disease
age females (hashimotos (papillary)
malignant
lymphoma,
Papillary (75- carcinoma)
80%),
follicular (10- elderly
(malignant
20%), undifferentiated lymphoma,
undiff
(1-5%),
medullary (3- carcinoma)
5%)
very rare
immunocomp
<1%
familial
F>M
F>M
Lab/Imaging
histology: Papillary
(fibrovascular core lined by
epithelial cells; finger-like;
enlarged, optically clear cells
w/ intranuclear grooves; little
orphan Annie's eyes Psammoma bodies);
Follicular (hard to diff from
adenoma; vascular &/or
transcaps invasion; Hurthle
cells - more agg lesions);
Medullary (C- cell
hyperplasia, amyloid
deposition, neuroendocrine +
stains - calcitonin, ectopic
hormones)
gross: transcapsular invasion
(follicular!!); necrosis
(malignant lymphoma)
histology: lymphocytic
thyroiditis, reactive
follicular centers (germinal
centers); destruction of
thyroid follicles, Hurthle
cells (abundant pink
reactive cytoplasm),
fibrosis
gross: enlarged thyroid,
bosselated (bumpy) w/
creamy surface from
lymphocytes
serum autoantibodies: antimicrosomal,
antithyroglobulin, anti TSHR, blocking antibodies
hyperthyroidism followed
by hypothyroidism (if gland
stops functioning)
histology: granulomatous
giant cells w/ lymphocyte
infiltrate (no giant cells seen
in Hashimotos!)
I-123: no uptake
(inflammation of thyroid
responsible for
hyperthyroidism)
VERY rare
Treatment
Complications
thyroidectomy,
radioactive iodine
Thyroid replacement
therapy if
hypothyroidism results
Disease
Clinical
Variants
Postpartum
Defining Characteristics
Pathogenesis
Etiologies
Epi
very
common!!
painless thyroiditis
appearing 1-2m postdelivery, lasts 2-5m
Risk factors
Lab/Imaging
Treatment
Complications
severe depression
MEN1
(Werners
syndrome)
Autosomal
dominant
0.25%
population
all ages, no
sex pref
4 gland hyperplasia
(sporadic dz only has single
parathyroid adenoma)
80% manifest
tumor by 5th
decade
first
manifestation
s occur earlier
than in
sporadic dz
adrenal hyperplasia
Osteitis fibrosa
cystica
MEN2A
medullary thyroid
germline mutation in RET
carcinoma or hyperplasia oncogene (tyrosine kinase
of thyroid C cells + pheo- receptor)
chromocytoma (adrenal
medullary tumor) +
parathyroid neoplasms
(adenoma or hyperplasia)
prophylactic
thyroidectomy
MEN2B
Pheochromocytoma +
thyroid medullary
carcinoma (or C- cell
hyperplasia) + mucosal
neuromas (neural tissue
nodules in GI tract or
mouth) + marfanoid
habitus
calcitonin secretion
prophylactic
thyroidectomy
hypercalcemia,
pathological fractures,
bone pain
hyperparathyroid bone
disease
some variants of
MEN2A have
Hirschsprungs dz
(megacolon from
lower intestinal
obstruction) or
cutaneous lichen
amyloidosis (upper
back)
Disease
Hypocalcemia
Clinical
Variants
(general)
Defining Characteristics
Pathogenesis
Etiologies
tetany (neuromusc
irritability, musc cramps,
tonic-clonic seizure;
elicited musc contractions
w/ Chvostek & Trousseau
signs), ocular abnl
(cataracts, papilledema,
pseudotumor cerebri),
prolonged QT interval &
nonspecific T wave
changes, anxiety,
confusion, depression,
intracranial sx (basal
ganglia calcification,
parkinsonism), dental
manifestations (dental
hypoplasia, failure of
eruption), macrocytic
megaloblastic anemia,
diarrhea
hypoparathyroidism (insuff
activity of parathyroid = low
PTH, hypocalcemia),
pseudohypoparathyroidism
(active parathyroid gland but
unresponsive end organs),
vit D def/insufficiency, vit D
dependent rickets I & II
(genetic deficiency of 1-a
hydroxylase prevents activation
of vit D in kidney), end organ
resistance to vit D;
renal failure (unable to make
RBCs, active vit D; can't
reabsorb Ca or eliminate P = inc
PTH)
activating defects (GOF) in
CaR of parathyroids(takes a
lower calcium to induce PTH;
would have nl PTH levels); PTH
resistance
meds (Lasix,
calcitonin, antineoplastic
agents, anticonvulsants,
citrated blood
products)
ALGORITHM:
low PTH? hypoPTH (gland
defect, no PTH production,
prob w/ CaR);
nl PTH? hypoPTH, transient
hypoPTH;
hi PTH? Renal failure, vitD
deficiency (would mean PTH
is less effective at raising
calcium so parathyroids
would continue to release
more...)
hi PTH?
Hyperparathyroidism,
familial hypocalcuric
hypercalcemia
Familial
hypercalcuric
hypocalcemia
Epi
Risk factors
Lab/Imaging
Treatment
acute - IV calcium
gluconate
chronic - calcium
carbonate
vitamin D - if PTH
problem, give calcitriol; if
vitD deficient, give
cholecalciferol (precursor)
Hypercalcemia (general)
Hypercalcemia
from
malignancy
sx related to sites of
calcium action/reg:
("stones, bones, groans,
psychic overtones")
- bone: fxs, osteoporosis,
osteomalacia, osteitis
fibrosa cystica
-kidney: nephrolithiasis,
nephrocalcinosis, polyuria
- CNS: depression,
seizures, obtundation,
muscular contractions
- EKG changes (shortened
QT interval)
- GI: gallstones, acute
pancreatitis, peptic ulcers
excess PTHrP
(cancers)
causes release
of PTH
humoral hypercalcemia of
malignancy (HHM) - major
cause of severe hypercalcemia,
usually due to ectopic PTHrP
SCC - lung
cancer, RCC,
lymphomas.
Local bone
metastasis
from breast Ca
or myeloma
PTH independent
hypercalcemia
FATIGUE, polyuria
symptomatic - fluids
followed by furosemide
once volume is
corrected; calcitonin
IM/SC (acute relief),
low PTH? Tumor induced
bisphosphonates
(PTHrP), granulomatous dz (slower relief); GCs (if
myeloma, granulomatous
or lymphoma, bone
dz, or vitD toxicity),
metastases, meds
dialysis - last resort
bone mineral density test
for osteoporosis
24h urine calcium &
creatinine clearance for
kidney fxn
Complications
Disease
Clinical
Variants
hypercalcemia
from
granuloma
dz
Familial
hypocalcuric
hypercalcemia
Defining Characteristics
Pathogenesis
Etiologies
PTH independent
hypercalcemia
PTH dependent
hypercalcemia
Epi
Hispanic
origin
Risk factors
FH
Lab/Imaging
Treatment
Complications
HyperPrimary
parathyroidism
PTH dependent
hypercalcemia
parathyroid
adenoma
25/100,000
cases in U.S.
path of parathyroid
adenoma: small tumor w/
encapsulated growth
pattern, lack of nl fat
component of PT, uniform if do not meet surgical
cells w/ round nuclei (tumor criteria, monitor blood
nests w/ dense chromatin), tests every 6 months
rare mitoses
osteitis fibrosa
cystica (see above)
path of parathyroid
carcinoma: much larger
than adenoma; bland
cytology (may have fibrosis,
scarring within tumor nests,
subtle infiltrative growth);
local invasion & metastasis
Secondary
Tertiary
dialysis patients!
possibly associated w/
duration of dialysis; can
occur in post-kidney
transplant patients
renal failure
vit D deficiency
brown tumors of
hyperparathyroidism
(reactive mass formed
secondarily to
microfractures and
hemorrhages as a
result of
multinucleated giant
cells and fibrous
tissue influx)
parathyroidectomy if PTH
cannot be controlled w/
meds
Disease
Hypoparathyroidism
Clinical
Variants
primary
Defining Characteristics
Pathogenesis
Etiologies
Epi
dysfunctional or hypofunctional
parathyroid gland usually
related to an autoimmune
process, infiltrative process
(hemochromatosis, Wilson's dz decreased serum PTH
(deficienct PTH secretion) copper, aluminum, breast
cancer metastasis,
granulomatous dz), or
magnesium deficiency
(chronic alcholism, malnutrition,
TPN, diuretics - thiazides,
furosemide, familial)
insuff activity of
parathyroid gland = low
PTH and hypocalcemia
Iatrogenic
Congenital
DiGeorge syndrome
(pharyngeal pouch
maldevelopment) posteriorly rotated ear,
flat nasal bridge,
hypertelorism (lots of
space btwn eyes), small
chin
Velocardiofacial syndrome
Familial
(APS-I)
candidiasis,
hypoparathyroidism,
Addison disease
Pseudo
Risk factors
Lab/Imaging
low (or nl) PTH, low
calcium, hi phosphate
Treatment
Complications
most common
cause of
hypocalcemia
agenesis/
dysgenesis of
parathyroids;
transient
(maternal
hypercalcemia
shuts down
baby's PTH),
syndromes
Disease
Vitamin D
deficiency /
insufficiency
Clinical
Variants
Defining Characteristics
rickets: bowed legs,
kyphosis, enlarged
epiphyses, metaphyseal
flaring, thickened wrists
from hi bone turnover,
rickettic rosary (palpable
nodules on ribs)
osteomalacia in adults
def = vitD < 50 mmol/L
insuff = vitD < 75 mmol/L
Hypophosphatemia
Pathogenesis
normal bone development
involves mixture of osteoid (nonmineralized component of
collagen, chondroitin sulfate, &
osteocalcin) with mineralized
component (calcium phosphate)
Epi
1 billion
limited
worldwide
sunlight
exposure,
inadequate
dietary intake,
kidney dz
(increased
vit D deficiency = dec calcium, excretion of
phosphate absorption = poor phos + inability
mineralization of bone -->
to create active
rickets in kids or
vitD), GI dz
osteomalacia in adults
(dec
absorption),
nutritional vitD deficiency,
def in vitD
hypophosphatemic rickets, 25- enzymes/
OHase def; 1,25-OHase def
receptors,
(renal failure), resistance to
resistance to
calcitriol
vitD
Hyperphosphatemia
Etiologies
hi PTH
hi FGF-23 (low
P, low vitD3)
low vitD3
PHEX mutation
Risk factors
Lab/Imaging
Treatment
Complications
Disease
Pituitary
adenoma
Clinical
Variants
(general)
Defining Characteristics
Pathogenesis
microadenomas (usually
secrete hormones) - <1cm;
prolactinomas, corticotroph
adenomas, somatotroph
adenomas
macroadenomas (usually
present w/ mass effect
without syndromic effect)
>1cm - bitemporal
heminopsia, diplopia
(CN3, 4, 6 palsy),
headache
Etiologies
Epi
MENI (menin
most common
mutation),
in adults (40other mutations 50 y.o.; M=F)
(CREB, Gs
protein, loss of
Rb, excessive
growth factor
production)
order of hormone
disruption: GH--> LH/FSH -> TSH --> ACTH
Prolactinoma
galactorrhea,
amenorrhea, decreased
libido, infertility,
amenorrhea/
hypogonadism,
osteoporosis, reduced
facial hair in men
30% of
pituitary
adenomas
Risk factors
Lab/Imaging
MRI: homogenously
contrast enhancing (no
cystic components or
calcifications)
pressure/mass effects,
hypersecretion of
hormones
dopamine agonists
(Bromocripitine,
Cabergoline) for tx of
microadenomas
no clinical manifestations
20% of
pituitary
adenomas
15% of
pituitary
adenomas
Complications
macroadenomas are
histology: loss of cellular
harder to manage (mass
heterogeneity, loss of
glandular structure (sheet effect)
like proliferation, neurocytic
rosettes around vessels,
papillary config, or ribbon
appearance), enlarged
nuclei; if severe necrosis/
hemorrhage think apoplexy!
Nonfunctional
Treatment
prolactin inhibits
gonadotropin release
& steroid prod in end
organs -->
amenorrhea or
secondary
surgery if macroadenoma hypogonadism in
w/ critical mass effect
men
(loss of vision, rapid
progression, spread to
osteoporosis
ICA), young pt w/ potential
for cure, no response/
recurrence (16%)
tolerance for med tx,
recurrence
surgery - loss of
anterior / posterior pit
fxn (DI)
Disease
Clinical
Variants
Somatotroph
Defining Characteristics
Gigantism (if adenoma
occurs in childhood before
closure of epiphyses)
acromegaly (if adenoma
occurs AFTER closure of
epiphyses) - large feet,
coarse/ enlarged /spongy
hands, auditory probs,
thickened skin/ lips, wide
nasal bridge, furrowed
brow), proportionally
enlarged organs, arthritis,
neuropathy
Gonadotroph
Pathogenesis
adenoma that secretes excess
GH
Epi
15% of
pituitary
adenomas
Risk factors
Lab/Imaging
elevated IGF-1 (even after
age- matching to
references)
OGTT suppression test
(hyperglycemia) results in
sustained elevation of GH
(nl the GH level would be
reduced w/ hyperglycemia)
impaired glucose
intolerance
insidious onset - check
pictures of pt from years
before
excess secreted by
adenoma could cause
precocious puberty
proliferative or neoplastic
conversion of cysts in
"intermediate lobe" --> ectopic
remnants of pharangeal
epithelium
hemorrhagic mass in
suprastellar space that
impinges on CNS structures -> calcifications, squamous
differentiation
somatic cell
more
mutations in B- common in
catenin gene kids (ages 1016)
10% of all
pediatric
intracranial
tumors
deposits
located within sellar
space or extends into
suprasellar space
Complications
1% of pituitary
adenomas
Pituitary
hyperplasia
Rathke's cleft
cysts
Treatment
5% of pituitary
adenomas
Thyrotroph
Craniopharyngioma
Etiologies
<5% of
masses
Disease
Clinical
Variants
Germinoma
Defining Characteristics
Pathogenesis
Etiologies
suprasellar tumor
Epi
Risk factors
Lab/Imaging
Treatment
Complications
Pituicytoma
Granular cell
tumor
suprasellar tumor
acquired
central
(neurosurgery,
head trauma,
tumors,
infiltrative dz,
idiopathic)
acquired
nephrogenic
(hypercalcemia,
hypokalemia,
lithium use,
amyloidosis,
Sjogrens)
Congenital
nephrogenic
(defective V2R; aquaporin
mutation)
surgical resection
Disease
ADH excess
Clinical
Variants
Syndrome of
Inapprop
ADH
(SIADH)
Defining Characteristics
Pathogenesis
Etiologies
inappropriate (nl/hi)
concentration of ADH for low
plasma osmolality --> water
retention & hypo-osmolality
despite euvolemic status
malignancy
(small cell lung para-neoplastic
synd; non-pulm
cancers), CNS
d/o (mass
lesions, inflam
dz - SLE,
meningitis,
degenerative
dz, subarach
hemorrhage,
trauma)
Epi
(general)
nl causes:
genetic/
familial, const
delay of
growth,
improper
measurement
abnl causes:
poor weight
gain,
osteochondrodysplasia,
genetic
syndromes,
hormone
problems
(thyroid def,
GH def, GC
excess)
Lab/Imaging
Treatment
drugs, pulm dz
(TB, pneumo,
mech
ventilation),
other (AIDS)
Short stature
Risk factors
90% of
referrals are
normal
most common
cause for
failure to
grow?? GC
excess
(Cushings)
Complications
Disease
Clinical
Variants
hypothalamic
defect
Pituitary
defect
Defining Characteristics
Pathogenesis
GHRH deficiency
GH deficiency
Etiologies
Epi
Risk factors
Lab/Imaging
hypothalamus
(GHRH def,
somatostatin
excess),
pituitary
(GHRH
receptors, GH1 gene to
encode GH,
transc factors
like Pit-1,
PROP1,
HESX1);
target (GHreceptors,
intact Jak/Stat
pathway, intact
IGF-1 and IGFBP3 response
systems)
possible craniopharyngioma
no GH released following
indirect stimulation testing
(hypoglycemia, a-2 agonist,
L-DOPA)
+GH released w/ direct
administration of GHRH (if
intact blood supply of
anterior pituitary), ghrelin,
or GHRP
Hypopituitarism
(general)
GH receptor mutations
(deletion, non-functional)
prevents end organs from
responding to GH
tumors - craniopharyngioma,
central defects in
pituitary hormones (all or optic glioma, pituitary adenoma
trauma - physical abuse, MVA
partial)
(usually posterior & anterior
defects bc severed neural stalk)
inflammation - histiocytosis,
hypophysitis
cranial radiation - usually
knocks GH out first
Idiopathic
inborn errors of pituitary
development - septic optic
dysplasia (SOD) - incomplete
development of
hypothalamus, septum
pellucidum, & optic nerves
Treatment
GH receptor
mutations?
(Laron
Syndrome)
congenital or
acquired - use
age of onset,
medical hx,
imaging,
associated
findings, &
impairment of
visual fields to
assess
suspect
genetic cause
if early onset,
no hx of
trauma/
radiation,
distinct growth
& hormone
phenotypes,
founder effect
Complications
Disease
Precocious
puberty
Clinical
Variants
MPHD
(general)
Defining Characteristics
Pathogenesis
Epi
Risk factors
Lab/Imaging
early maternal
menarche, low
birth weight, inc
weight gain
(obesity) in
childhood,
international
adoption,
estrogenic
chemicals,
absence of
father in
household,
FEMALES
Treatment
Complications
Central
Etiologies
caloric intake
(excess
adipose)
Disease
McCuneAlbright
Syndrome
Clinical
Variants
Non-central
Defining Characteristics
Pathogenesis
Epi
Risk factors
Lab/Imaging
Treatment
gonadotropin - independent
(decreased FSH/LH, increased
testosterone or estradiol)
autonomous gonadal
activation- McCune-Albright
Syndrome (GNAS activating;
see below), activating mutation
of LH receptor gene
adrenal d/o - CAH, adrenal
tumor (muscle development +
small testes)
exogenous exposure to sex
steroids
Tumor - ovarian cysts
(Granulosa cell / androgen
producing), Leydig cell tumors
in testicle, hCG producing
tumors in liver
van Wyk-Grumbach syndrome
(see below)
early non-central puberty + activating mutation in GNAS mutation in the
gene that
hyperthyroidism
causes ovary/testicle to
codes for the
develop independently of
TRIAD: non-central
stimulation by gonadotropins - alpha subunit
of the
precocious puberty, caf- -> secretion of estradiol/
stimulatory G
testosterone--> precocious
au-lait skin findings,
protein (Gsa)
puberty
hyperostosis fibrous
dysplasia
Excess estrogen exposure =
increased growth velocity &
marked advancement in skeletal
maturity
ovary will be hyperfunctional
for some time but then
involutes; once brain senses
that bone age is appropriate,
pulsatile GnRH & LH/FSH
secretion will begin,
normalizing puberty
Van WykGrumbach
Syndrome
Etiologies
only condition w/
precocious puberty w/o
bone age advancement
(growth arrest)!!
Primary hypothyroid +
precocious non-central
puberty
Complications
Disease
Turner
Syndrome
Polycystic
ovary
syndrome
(PCOS)
Clinical
Variants
Defining Characteristics
Pathogenesis
secondary amenorrhea,
hirsutism/acne, infertility,
obesity, hyperlipidemia,
insulin resistance
Diagnosis REQUIRES 2 of
3 criteria: oligomenorrhea,
any evidence of
hyperandrogenism
(clinical hirsutism, acne;
biochem findings), PCOS
appearing ovaries on U/S
(>12 cysts, 2-9 mm)
androgens provoke
accelerated GnRH pulsatility,
causing enhanced release of
LH and subsequent production
of more ovarian androgens
acanthosis nigricans
Etiologies
Epi
Risk factors
most
common
recognizable
cause of
spont Ab
median age of
dx? 15 y.o.
6-10%
prevalence
accounts for
~75%
anovulatory
infertility
FH
Lab/Imaging
Treatment
amniocentesis: abnl
chromosomes
karyotype: One X
chromosome with absent 46th
chromosome
PE: signs of coarct & HF
(crackles, displaced apical
impulse, hepatomegaly, early
systolic click), non-pitting
edema (sign of lymph prob)
Pelvic XR - maldeveloped
head of femur, displaced from
foramen - DISLOCATED HIP
ECHO - bicuspid aortic valve
Renal/pelvic U/S - horsehoe
kidney, duplicated UT
short stature - GH
replacement
DX OF EXCLUSION:
supportive data?
Hyperandrogenism,
oligoanovulation, polycystic
ovaries on U/S, obesity,
IR/DM, hi LH/FSH ratio
Complications
hypothyroidism,
T1DM, T2DM,
osteoporosis,
premature ovarian failure - premature death
add androgens when
(related to CVD,
appropriate for puberty
coarct), aortic
dissection, ovarian
multi-disciplinary
failure/ dysgenesis
interactions w/ cardio,
psych, ENT,
progressive
endocrinology, etc
sensorineural
deafness, probs w/
social intxns & visual/
spatial defects
Y chrom mosaics - inc
risk for gonadoblastomas -->
dysgerminoma require ovary
removal!!
metformin for
hyperinsulinemia &
possible improved
response to clomid
ovarian wedge resection
for hyperandrogenemia
clomiphene,
gonadotropins, or
aromatase inhibitors for
anovulation
live birth rate better w/
clomid + met or clomid
alone (NOT met alone)
increased risk of
endometrial cancer
(unopposed estrogen),
DM, CVD, obstetric
risks, depression,
anxiety, infertility
Disease
Abnormal
uterine
bleeding (AUB)
Clinical
Variants
(general)
Defining Characteristics
any disruption from
normal cycle (24-35d x 46d, 30 ml blood loss)
Pathogenesis
structural or functional
abnormality??
Etiologies
PALM-COEIM
P (polyp), A
(adenomyosis
Ovulatory v. anovulatory?? Ask ), L (leioabout timing (ovulatory bleeding myomas) M
oligomenorrhea - cycle
more regular due to
intervals > 35 days
(malignancy,
programmed shedding of
polymenorrhea - cycle
hyperplasia), C
corpus luteum)
intervals < 24d
(coagulopathy
menorrhagia - normal
), O (ovulat
intervals but excessive flow absent menstrual flow during pill dysfxn), E
free week of OCP - think
or duration
(endometrial),
progesterone breakthrough
metrorrhagia - irregular
I (Iatrogenic),
bleeding (use short interval of
intervals, normal flow or
M (Mullerian
estrogen)
duration
anomalies)
menometrorrhagia irregular intervals,
excessive flow or duration
Epi
2nd most
common
reason for
OB/GYN
visits
Risk factors
perimenopause
most
common
cause of
adolescent
hospital
admissions
Lab/Imaging
Treatment
Pregnancy test!!!
CBC (R/O anemia,
thrombocytopenia)
TSH (hypo/hyperthyroidism
a/w AUB)
cervical cancer screening
chlamydia (hi risk patients)
screening for bleeding d/o
(adolescents)
endometrial bx (>40 y.o.,
prolonged anovulation)
transvaginal U/S (hi risk for
cancer/ hyperplasia if
endometrial stripe > 5 mm)
hysteroscopy (dx, tx
symptomatic intrauterine
pathology)
Anovulatory bleeding:
progesterone (oral tx,
Mirena IUD) - induces
regular bleeding &
prevents endomet
hyperplasia (opposes
estrogen), combined
OCPs, estrogen tx (only if
hemorrhaging w/ low
hematocrit), D&C
(hemodynamically
unstable)
Ovulatory bleeding:
NSAIDs (dec
prostaglandin), OCPs,
Mirena IUD, GnRH
agonists (preop pts),
antifibrinolytics
(tranexamic acid)
surgery: endometrial
ablation, hysterectomy
Menstrual diaries
Polyps
intermenstrual spotting
Adenomyosis
painful periods
Leiomyomas
(fibroids)
Coagulopathy
most common
lesion
causing AUB
in
reproductive
aged women
Ovulatory
dysfunction
Endocrinopathy
usually PCOS
Endometrial
endometritis, hyperplasia
obese, elderly,
postmenopausal,
PCOS
20% w/ heavy
menstrual
bleeding have
underlying
bleeding d/o
CBC/platelets
prothrombin time
partial thromboplastin time
PCOS
Complications
Disease
Clinical
Defining Characteristics
Pathogenesis
Variants
Inflammatory bleeding without relation vulvitis, vaginitis, cervicitis,
endometritis, salpingitis, PID
to menses
Iatrogenic
Pregnancy
bleeding
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
Chronic
HTN
hi BP before pregnancy, or
<20 weeks gestational age
mosy
common med
comp of
pregnancy
6-8% of all
live births
17.6% of
maternal
deaths in U.S.
hi BP >20 weeks
gestational age
BP > 140/90, occuring
after 20 weeks without
proteinuria
Preeclampsia
maternal
starts w/ up & down BP,
extremes of age progresses to >140/90, then
proteinuria followed by
1st child
signs & sx of severe preeclampsia; if left untreated,
chronic HTN,
will progress to eclampsia
vascular
disease, DM
hx of HTN in
pregnancy
minority groups
vasoconstriction/ vasospasm
[circul vasoconstrictors + endog
vasoconstrictors -> endothelial
damage (dec prostacyclin, inc
TbxA2) --> primary DIC]
HELLP syndrome
(>24wks): hemolysis,
elevated liver enzymes, low
platelets
improper trophoblast
implantation --> immunologic
response
Eclampsia
cause of
maternal
mortality
DELIVERY!!
HELLP: liver
hematomas, DIC
If <32 weeks, give
fetal risks: IUGR,
oligohydramnios
antenatal
(decreased amniotic
corticosteroids &
stabilize w/ MgSO4 (anti- fluid = dec urine output
from blood flow shunt
seizures), antito brain/heart/adrenals
hypertensives, & LD
& away from kidneys),
bedrest for 48h before
placental
delivering
infarct/abruption,
prematurity
consequences,
uteroplacental
insufficiency, perinatal
death
maternal risks: CNS
problems (stroke,
seizures), DIC, C/S,
renal failure, hepatic
failure, death
stabilization (MgSO4,
antihypertensives),
assessment for maternal
sequelae, and delivery
Disease
Clinical
Defining Characteristics
Variants
Atypical pre- vague RUQ or epigastric
eclampsia
discomfort, small
headache, incidental
thrombocytopenia
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
aneuploidy - monosomy X0 or
trisomy 16
Threatened
Inevitable - os is wide
open, lots of blood
missed/incomplete - some
tissue still present
Complete - uterus is empty
and hCG levels drop off
following day
Ectopic
pregnancy
50% of 1st
trimester
bleeding
usually no intervention is
required; however, if
tissue remains (missed) D&C or medical tx
heavy bleeding? D&C
pregnancy/ implantation of
Chlamydia gestational sac OUTSIDE of the replicates
uterus
intracell &
Bleeding + pain!!
lyses cells
Adnexal mass + tenderness interstitial tubal pregnancy
most dangerous bc least
rupture?? Unstable vitals, distensible!
positive pregnancy test,
Ampullary end of Fallopian
diffuse tenderness,
tube and abdomen most
bleeding (low HCT)
conducive to embryonic
development
1st trimester bleeding
1-2%
prevalence
prior ectopic,
PID, surgery,
endometriosis
10% mortality w/
rupture
INFERTILITY
chronic pain
Placental
abruption
15% of 3rd
trim bleeding
1:120
deliveries
trauma,
U/S NOT helpful, dx is
smoking/
clinical (NO CERVICAL
cocaine,
EXAM!!)
multiparity, HTN,
prior abruption,
AMA
fetal anemia,
Disease
Clinical
Variants
Placenta previa
Defining Characteristics
3rd trimester bleeding
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
10% of 3rd
trim bleeding
PAINLESS bleeding
Treatment
fetalComplications
hypoxia (cerebral
palsy, seizures),
immediate hospitalization,
maternal hemorrhage
IV access/ fluids/ type &
shock,
cross
C/S delivery if unstable
or term
DIC (abruption)
noncontracting
uterus
(UTERINE
ATONY)
5% of
deliveries
uterine atony: hi
parity,
overdistention
uterine atony - (twins,
most common macrosomia),
cause of post- prolonged labor,
partum
rapid labor,
hemorrhage prolonged use of
induction
agents,
chorioamnionitis,
prior history
epithelial
(most
aggressive
form, more
common in
older
women)
Endometrial
cancer
primarily affecting
peri/postmenopausal
women
Leading
cause of
death for gyn
malig
1/70 women
increased
estrogen
synthesis
(obesity,
granulosa cell
tumors)
decreased
estrogen
metabolism
(hepatic dz)
inapprop HRT
(estrogen only)
atony? Pitocin-like
oxytocin, prostaglandins
retained
placental frags:
prior C/S, uterine
curretage,
accreta
coagulation
disorders
most
common gyn
malignancy
in U.S.
FH of ovarian
cancer,
advanced age,
nulliparity,
North American/
North European
descent, PMH of
breast/ colon/
uterine cancer
+ postoperative
treatment w/ IV
chemotherapy or clinical
trials
age > 60
obesity
unopposed
estrogen
chronic
anovulation
(PCOS)
tamoxifen use
endometrial
hyperplasia
(atypical
complex)
surgery - TAH
endometrial biopsy perform if abnl bleeding +
>4mm endometrial
thickness on U/S; abnl
bleeding + tamoxifen use;
post-menopausal bleeding;
change in bleeding pattern
in women on HRT or perimenopausal
no screening test so
patients present at
later stage (Stage III) -> higher mortality
Disease
Clinical
Variants
Cervical cancer Squamous
(80-90%)
Defining Characteristics
Pathogenesis
HPV 16 & 18
POST-COITAL BLEEDING
adenocarcinoma
(10-20%)
Epi
globally, most
common gyn
malignancy
(lower in U.S.
bc screening)
3rd most
common gyn
malignancy
Germ cell
Ovarian Dys- dysplastic germ cells
tumors of ovary germinoma (similar to testicular
seminoma)
Etiologies
Risk factors
Lab/Imaging
young women,
often a/w
pregnancy
usually NO hormone
production
Treatment
Stage I-II A: radical
surgery/ hysterectomy +
additional cervical tissue
stage I - cervix
Stage II - upper vag
Stage III - lower vag
radiosensitive, treated
malignant but good
conservatively (R/O mixed prognosis
germ cell tumor!!)
Endodermal
sinus (yolk
sac) tumor
young women
combo of chemo,
radiation, & surgery
improve 5y survival
markedly hemorrhagic
produces hCG!!
Complications
malignant tumor
Disease
Ovarian
Teratoma
Clinical
Variants
(general)
Defining Characteristics
benign teratomas? Brain
& choroid plexus (nonfunctioning)
Pathogenesis
germ cell tumors that make
somatic tissue
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
gross:
- hemorrhage w/ hair, etc?
think teratoma infarction
- cystic teratoma - filled w/
yellow solidified sebum (nl
in skin); some have teeth at risk for rupture
- multiple glial nodules?
Benign teratoma (brain)
Complications
torsion of cystic
teratoma (acute abd
pain resulting form
vasculature
strangulation -->
teratoma
hemorrhagic
infarction)
teratomas w/ teeth at risk for rupture
Immature
Mature
carcinoid (serotonin-like
substances)
Ovarian Theca
cell tumor
MOSTLY benign!
Usually produces
estrogens
Ovarian
fibroma
Ovarian
Granulosa cell
tumor (GCT)
malignancy shown by
recurrence > 15 years
later
a/w uterine
endometrioid
carcinoma
(unopposed
estrogen)
Disease
Clinical
Variants
Sertoli- Leydig
cell tumor of
ovary
Germ cell
tumors of
testes
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
benign masculinizing
tumor --> clitormegaly,
hirsutism
(general)
90% of
testicular
neoplasms
Lab/Imaging
Caucasians
cryptorchidism
familial
clustering
Treatment
radical orchidectomy +
chemo/radiation
Complications
MALIGNANT in
adults
testicular
dysgenesis
(Klinefelters)
Intratubular
germ cell
neoplasia
(ITGCN)
Seminoma
asymptomatic,
sometimes pain/
discomfort
5% of
contralateral
testes of men
who had
orchiectomy
for germ cell
neoplasm
embryonal
carcinoma
composed of primitive
undifferentiated epithelia
Teratoma
Sex cord
Sertolistromal tumors Leydig cell
of testes
tumors
5% of
testicular
neoplasms
Disease
Squamous cell
carcinoma of
penis
Clinical
Variants
Defining Characteristics
Pathogenesis
Carcinoma of
scrotum
Periductal
mastitis
Duct ectasia
Etiologies
development of inflammatory
cells in the periductal area of
breast
Epi
<1% of male
cancers in
U.S.
More
common in
Asia, Africa,
S. America
Risk factors
Lab/Imaging
Treatment
Complications
poor genital
Bowenoid papulosis - HPV
related precursor lesion
hygiene in
uncircumcised (rarely progresses)
men;
Bowen disease -gray or
erythematous plaque; risk of
HPV 16&18
invasion 10%
other HPV histology: loss of polarity,
genital warts
mitotic figures, disorganized
growth that occupies full
thickness of epithelium (rather
than more abundant
cytoplasm at top like nl);
KERATIN PEARLS
No predisposition to
carcinoma!
small risk of
carcinoma
development
NO PAIN
Papilloma
unilateral, non-milky
nipple discharge from 1
duct orifice, +/- blood
proliferative lesion
Papillary
carcinoma
~ 60 years old
histology: fibrovascular
core, epithelial lining
WITHOUT myoepithelial
layer; overlapping nuclei
usually good
prognosis bc bloody
discharge is alarming
enough to seek help
Disease
Cysts (breasts)
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
Epi
VERY
common!
Risk factors
reproductive
aged women
Fibroadenoma
teenagers
African
Americans
> age 40
Adenosis
Usual
hyperplasia
aspiration if extremely
painful
recurrence
MUST BE TOTALLY
EXCISED
absolutely recurrent
so excision required!
Complications
Phyllodes
tumor
Sclerosing
adenosis
Treatment
Benign
sclerotic collagenous
material causes FIRM
breasts
Lab/Imaging
histology: proliferation of
both epithelial &
myoepithelial cells into the
lumen (creates bridges),
phenotypic mixture of cells
(linear, oval, narrowed
spaces) but no pattern of
identical mutations
mammogram: calcifications
in the lobule unit spaces
Disease
Atypical
hyperplasia
(ADH)
Ductal
Carcinoma In
Situ (DCIS)
Clinical
Variants
(general)
ductal,
lobular
Low grade
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
deletions in
chromosomes
16 &17 -->
"Roman
bridge"
structure
excision of lesion w/
histology: has some
needle core biopsy
cytologic features of low
grade DCIS; usual
hyperplasia + clonal lesions
like Roman bridges!
SMALLER than DCIS;
calcifications in lumen of
spaces
non-motile mass on
breast exam
deletions in
chromosomes
16 &17 -->
"Roman
bridge"
structure
Complete excision +
histology: monoclonal
radiation
population of low
grade,mutated cells; round/
punched out spaces
(Arches of Roman Bridge!);
calcium phosphate crystals
(stain purple), no
myoepithelial layer!
atypical hyperplasia +
persistent mutations --> low
grade DCIS
High grade
hi risk of invasion!!!
Recurrence w/I 3y if
not adequately
excised
mammogram: calcifications
that form mold/cast in duct
(linear calcifications)
gross: linear pattern;
necrotic material in the duct
(yellow)
Paget's disease
of the nipple
AVOID corticosteroids
Disease
Infiltrating
ductal
carcinoma,
Clinical
Variants
Low grade
Defining Characteristics
receptors for estrogen &
progesterone
non-motile mass
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
potential to invade
lymphatic spaces!
histology: infiltrating
pattern w/ remnants of
DCIS; fibrotic (lots of
collagen! byproduct of
vascularization); low grade
nuclei, gland formation
invasive into stroma
High grade
determined by
differentiation (gland
formation), nuclear
anaplasia, and mitotic
figures
non-motile mass
histology: poor gland
formation, necrotic cells,
mitotic figures
Atypical lobular
hyperplasia
(ALH)
Lobular
carcinoma in
situ (LCIS)
non-calcifying lesion so
hard to find!!
Infiltrating
lobular
carcinoma
deletion of
gene for Ecadherin
adhesion
molecules
mammogram: no
calcifications
histology: proliferation of
round cells within the
lobule (bag of marbles)
10% of
invasive
breast
carcinomas
mammogram: no
calcifications - difficult to
detect!
Gross: looks like fatty
fibrous breast but can't see
lesion
responds to tamoxifen!!
Medullary
carcinoma
BRCA1/2
2-3% of
infiltrating
ductal
carcinomas
histology: rounded
carcinomas w/ lymphocytic
infiltration!
Disease
Clinical
Variants
Mucinous
(colloid)
carcinoma
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
BRCA1/2 mutations - FH
breast cancer < age 50,
FH of papillary ovarian
cancer; triple negative
(ER/PR, HER2)
estrogen
exposure
(endogenous
or exogenous)
hi risk
mutations
(BRCA1,2;
PTEN, TP53)
good prognosis if
properly diagnosed!!
Complications
#1 cancer
among U.S.
women; #2
cause of
cancer
mortality in
women
increased age
Caucasians
(after age 45;
before age 45,
AA have higher
risk) > AA> NA,
Hispanic, Asian
staged based on
tumor grade, ER/PR
stattus, HER2 status,
lymph node status
(axillary lymph nodes
first!!)
mortality
early menarche,
greatest in AA nulliparity, late
women
menopause,
OCP (but
decreased risk
affects 1/8
for endo/ovarian
women
Ca), estrogen
replacement tx,
obesity, alcohol,
FH
Dysmenorrhea (general)
Treatment
rounded periphery
lesions that also
resemble fibroadenomas
(BUT fibroadenomas
appear at younger age
usually & would have been
noticed in earlier
mammograms)
ER/PR positive
Breast cancer
Lab/Imaging
sentinel LN studies
50% of
menstruating
women
OCPs
NSAIDs for moderate pain
5-10% dysmen
affects QoL
PE: nl except some
tenderness
prostaglandin
synthetase inhibitors
Disease
Chronic Pelvic
Pain
Clinical
Variants
Secondary
(general)
Endometriosis
Defining Characteristics
Etiologies
underlying pathology:
endometriosis, adenomyosis,
fibroids, congenital uterine
anomalies (bicornuate, septate,
pain begins 3-5d prior to
period, relieved by period non-communicating horn),
cervical stenosis, endometrial
onset
polyps, PID
less likely to respond to
NSAIDs or OCPs
multi-factorial
non-cyclical pain > 6m
GYN: endometriosis, pelvic
adhesions, PID, adenomyosis,uterine myomas
GI: IBS, IBD, constipation,
colitis, diverticulitis
Urologic: IC, chronic UTI,
urinary calculi, radiation cystitis
MSK: pelvic floor pain,
fibromyalgia, low back pain,
nerve pain
Epi
Risk factors
endometrial tissues (glands & Endometrial stroma) that occur outside the retrograde
severity of pelvic pain =/= uterus
menstruation,
lymphatic
pathology by laparoscopy
dissemination,
Immunologic abnl cause inc
vascular
pelvic pain, infertility
presence of circulating
dissemination,
autoantibodies, inc #
peritoneal macrophages, dec direct invasion,
uretotubal
T-cell reactivity & NK activit
most common area?
Posterior cul-de-sac
protective factors? Habits that in situ
decrease peripheral estrogen (congenital) celomic
(exercise, smoking)
metaplasia,
Wolffian duct
remnants,
Mullerian duct
remnants
Pelvic
adhesions
(asherman's
syndrome)
Pelvic
venous
congestion
syndrome
Pathogenesis
infection, pelvic
bands of scar tissue form
between two pelvic organs --> surgery,
trauma
infertility & chronic pain
Lab/Imaging
PE: abd & vaginal exam
may reveal underlying
lesion
Treatment
Complications
analgesics
treatment of underlying
cause
U/S of vaginal/abd,
laparoscopy, hysteroscopy
15% of
reproductive
age women
h/o sexual or
impt to do rectovaginal &
physical abuse bimanual exam in these
patients!
PTSD
Laparoscopy - nl in 35-40%,
drug/alcohol
endometriosis in 30%,
abuse
pelvic adhesions in 25%
multidisciplinary (bc
50% of women have
usually multiple causes of comorbid psych
pain)
diseases
(DEPRESSION!)
include mental health
provider (counseling +
med tx way more effective
than med tx alone!)
1. NSAIDs
2. consideration of
narcotics
3. chronic pain meds
(gabapentin, topamax,
valproic acid, antidepressants)
cause of
chronic pelvic
pain in young
women
3-15% of
general
population; 2050% of
infertile
population
FH, increased
exposure to
menstruation
(early menarche,
nulliparity), flow
obstruction,
obesity
presumptive tx before
laparoscopy (interrupt
menstrual cycle) monophasic OCP (daily
hi dose progestin) / vag
ring/ patch for 3m
NSAIDs, Depo-Provera,
GnRH analogs (Lupron,
Synarel, Zoladex)
surgery? Laparoscopic
destruction of lesions,
bilateral uterosacral
ligament resection,
hysterectomy
Disease
Sexually
transmitted
infections
Clinical
Variants
Pelvic floor
dysfunction
(general)
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Interstitial
cystitis (80%)
19 million new
bacteria
cases/ yr
(gonorrhea,
chlamydia,
syphilis,
chancroid)
viruses (HIV,
HPV, HSV, hep
A/B/C)
parasites
(Trichomona,
pubic lice)
Lab/Imaging
PE: examination of pelvic
floor muscles -->
tenderness and pain in
bladder, vagina, vulva, or
perineum
NAATs more sensitive
(however, not FDA
approved for all receptive
sites)
Treatment
Complications
Urethricitis
dysuria, urinary
frequency, intermittent
penile discharge
gonorrhea, chlamydia,
Mycoplasma genitalium
GC (5-20%),
CT (15-40%),
NGU (non
gonoccocal
urethritis - all
other agents)
frequently asymptomatic
chlamydia, gonorrhea,
trichomonas, herpes, BV
chlamydia
recurrent or persistent
infection (30% of pts) - retreat if non-compliant,
conjunctivitis? a/w
think Trichomonas or
CT autoinoculation
resistant ureaplasma or
mycoplasma
PE: purulent / mucopurulent azithromycin - 1g PO
once OR doxycycline
endocervical exudate;
easily induced endocervical 100mg/ PO bid x7d
bleeding
GC/CT NAAT
Cervicitis
Azithromycin - 1g PO
once if NGU infection OR
doxycycline 100mg/ PO
bid x7d
Disease
Clinical
Variants
Genital
ulcers
Vaginal
discharge
Defining Characteristics
Pathogenesis
Trichomonas, bacterial
vaginosis
Candidiasis: cottage
cheese d/c
BV: fishy odor
Etiologies
Epi
majority due
to HSV or
syphilis
Granuloma mostly in
Caribbean
noninfectious
sources?
Yeast, fixed
drug eruption,
psoriasis
HSV - 1/4
young people
Risk factors
Lab/Imaging
underlying dz
syphilis serology, herpes
(immunocomp, culture/ PCR serology
Crohns),
residence, travel
hx
# partners
Treatment
Complications
Trich (15-20%),
BV (40-45%;
a/w sex), vulvovaginal
candidiasis (2025%)
Genital
warts
Proctitis
PID
DGI
HPV
monoarticular septic
arthritis of large joints;
tenosynovitis/ dermatitis
(rash); 1-3% w/ mucosal
infection; fever/ chills
septic vasculitis - pustula
(pus filled vesicle)
MSM, women w/
rectal
intercourse
very
uncommon
(decline in
etiologic
strains for unk
reason)
complement
deficiency
patients
younger,
sexually active
women
Disease
Clinical
Variants
Tubo-ovarian
abscess
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
PID + IUD
Lab/Imaging
Treatment
Complications
Adrenal
insufficiency
(general)
hyponatremia,
hypercalcemia,
weakness/ fatigue/
anorexia, weight loss,
postural hypotension,
nausea, diarrhea,
myalgia/ arthalgia
Primary
Symptoms above in gen
(ADDISONS category + adrenal
)
calcification (fungal/ TB
cause), vitiligo
(autoimmune attack of
melanocytes),
hyperpigmentation (ACTH
binds melanocytes),
hyperkalemia (loss of zona
glomerulosa = loss of
aldosterone = inc K+)
0.3% of TB
patients
Addisons;
85% of pts
who die from
TB have
adrenal involv
chronic replacement of
GC & MC
hyperpigmentation
does NOT resolve
even post-tx
Disease
Clinical
Variants
Secondary
Defining Characteristics
NORMAL POTASSIUM
LEVELS!!!! + symptoms
above in general category
Pathogenesis
hypothalamic/pit dysfxn --> no
ACTH produced or secreted -->
no stimulation of adrenals -->
insuff
no ACTH = adrenal atrophy =
adrenal insuff
Stopping GCs suddenly will
cause adrenal insuff - MUST
wean these patients & test for
HPA axis responsiveness
Etiologies
Epi
Risk factors
HIV,
iatrogenic
(most
common!!) prolonged GC
treatment
Lab/Imaging
LOW ACTH (unable to
produce so adrenals aren't
stimulated)
short cosyntropin test - IV
ACTH will cause slight
increase in cortisol
secretion (suggests partial
insuff)
HP axis dz
(tumors of pit,
hypothalamus,
infiltrative dz,
trauma)
Adrenal
tuberculosis
Autoimmune
adrenal
disease
WaterhouseFriderichsen
syndrome
acute hemorrhagic
necrosis /infarct of
adrenal glands as a
complication of DIC
child presents w/ adrenal
insufficiency + infection +
pic of hemorrhagic
adrenals
Polyglandular Type I
Autoimmune
Disease (PGA)
a/w systemic
more
infection:
common in
children
Neisseria
meningitidis,
Pseudomonas,
H.influenzae,
Staph
gross: hemorrhage of
adrenals
histology: massive
extravasation of RBCs in
cortex
autosomal
recessive
Other disorders?
Pernicious anemia,
alopecia, malabsorption,
chronic active hepatitis
CHILDHOOD
Type II
autosomal
dominant
HLA B8 (DW3),
DR3, DR4
Treatment
Chronic replacement of
GC
Complications
Disease
Clinical
Variants
Adrenal Leukodystrophy
Congenital
Adrenal
Hyperplasia
(CAH)
Defining Characteristics
Pathogenesis
(general)
Etiologies
Epi
Risk factors
Lab/Imaging
X-linked
recessive
mutation of
ABCD1 gene
(MALES only)
25-35% of
"idiopathic"
Addisons now
known as mild
ALD
neuropsychiatric testing
most
common of
CAH!!
Cortrosyn stimulation
testing = gold standard for
dx - measures 17-OH
progesterone & cortisol levels
pre& post stimulation
Treatment
loss of 11B-hydroxylase
prevents formation of
corticosterone & aldosterone =
accumulation of
deoxycortisone, which is able
NO ALDOSTERONE &
to bind aldosterone receptor
CORTISOL; HOWEVER,
DEOXYCORTICOSTERON and act as a powerful
E STILL ABLE TO BIND
mineralocorticoid = HTN
MR
11B- hydroxylase also used to
make cortisol from 11deoxycortisol, thus these
patients will have adrenal insuff
and accumulation of 11deoxycortisol
pathway is shunted towards
the androgens
1:15,000
Complications
Disease
Clinical
Defining Characteristics
Variants
17aadrenal insuff, ambiguous
hydroxylase genitalia, sexual
deficiency
infantilism, primary
amenorrhea, HTN
NO CORTISOL OR SEX
ANDROGENS; EXCESS
ALDOSTERONE
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
3B-hydroxysteroid
dehydrogen
ase II
Cushing
syndrome/
disease
(general)
loss of 3B-hydroxysteroid
dehydrogenase results in
decreased production of all 3
groups of adrenal steroids,
which include
mineralocorticoids,
glucocorticoids, and sex
steroids
much less
common
adrenal disease:
adrenalectomy (last
resort) + radiation
Disease
Clinical
Variants
Pituitary
ACTH
production
Defining Characteristics
Pathogenesis
Etiologies
Epi
70-80% of
endogenous
Cushings
Females 5:1
Carney
complex
Cushing syndrome
Adreno-cortical (general)
adenoma
Conn
syndrome
HTN, hypokalemia,
alkalosis, hi urinary
potassium
aldosterone-producing
adrenocortical adenoma
Lab/Imaging
gross: enlarged cortex of
adrenal
20> plasma ACTH < 200
medical suppression w/
dexamethasone (presence
of negative feedback still so
urine free cortisol
suppressed) - distinguishes
Cushing dz from syndrome
Treatment
pituitary disease: transsphenoidal resection +
radiation
Complications
complications of transsphenoidal resection?
Transient DI
(disruption of post pit),
CSF leak, meningitis
post-surgery cortisol
supplementation until HPA
axis recovers
panhypopituitarism
from radiation
therapy (90%
patients over 10y
time frame)
hypercortisolism +
lentiginosis (spotty
pigmentation) + cardiac
myxoma, endocrine
autonomous cAMP pathway
tumors (adrenal cortical,
GH, or thyroid adenomas/ stimulation downstream
carcinomas, melanocytic
schwanomas, testicular or
breast ductal carcinomas
kids: most often functional - loss of heterozygosity involving autosomal
tumor suppressor gene leading dominant
-> Cushing syndrome +
to activation of cAMP signal;
mutation
virilization
succession of mutations cause
progression from:
adults: functional & nonhyperplasia --> adenoma -->
functional; Cushing>
carcinoma
hyperaldosteronism >
virilization
Risk factors
very rare
F>M
adenomas in
kids usually
occur at age
<5
adrenalectomy (last
resort) + radiation
panhypopituitarism
from radiation therapy
(90% patients over
10y time frame)
Nelson's syndrome unrepressed growth of
pituitary adenoma
from hi ACTH levels
(complication of
adrenalectomy)
Disease
Clinical
Variants
Adreno-cortical
carcinoma
Defining Characteristics
Pathogenesis
Etiologies
Epi
kids: ~4y.o.
adults: ~45yo
F>M
very rare
compared to
adenomas
Risk factors
Lab/Imaging
gross: large mass +
hemorrhage + necrosis in
cortical section (yellow)
histology: sheets of
eosinophilic to clear cells; hi
nuclear polymorphism,
atypical mitotic figures,
necrosis of larger cells
Treatment
Complications
Adrenal
metastasis
Secondary
hypertension
(general)
hyperaldosteronism,
MC excess,
pheochromocytoma,
renal artery
stenosis, renal
disease,
endocrine
causes
(Cushings,
hypo/hyperthyroidism,
OSA)
Pheochromo onset of HTN at young age, adrenal medullary
syndromes:
cytoma
episodic HTN,
(neuroendocrine) tumor arising MEN2, neuropalpitations, tachycardia, from chromaffin cells =
fibromatosis,
tremor, weakness, pallor, production of catecholamines von HippelLindau, Sturgeanxiety (adrenergic stim),
= stimulation of alpha & beta
Weber
retinopathy, hyperglycemia, receptors = inc BP,
polyuria/ polydypsia, chest contractility, & HR =
pain, nausea, hypercerebrovascular &
reninemia (orthostatic
cardiovascular consequences
hypotension), ileus
resistant HTN (BP>140/90
w/ full doses of >3 meds +
suddent onset +
younger/older age at onset)
Classic triad??
Palpitations w/ tachycardia,
headache, perspiration
(drenching sweats)
most common
causes?
Hyperaldosterone,
renal dz
rare
usually adults
(50y.o.)
urinary catecholamine
metabolites (vanillylmandelic
acid, metanephrines) - might
require rpt testing bc episodic
nature of tumor
Clonidine suppression testdistinguishes pheo from false
positive inc in catech
MRI/CT nodules? last option
gross: gray-tan
hemorrhagic mass > 1cm;
bilateral in familial cases (a/w
syndromes); displacement of
cortex
histology: polygonal spindle cells, nested
pattern (Zellballen),
extensive vascular pattern,
variable nuclear
pleomorphism
preoperative alpha-adrenergic
blockers (lowers
BP&catech surges;
Phenoxy-benzamine,
terazosin)
B-adrenergic blockers
(only start AFTER ablockers; used for
tachycardia)
SURGERY required!!
50% 5y survival in
malignant tumors
certain drugs can
interfere w/
catecholamine assay
so might need to
change meds around
Disease
Clinical
Defining Characteristics
Pathogenesis
Variants
Hyperaldost adrenocortical
Conn's syndrome - HTN,
eronism
hyperfunction
hypokalemia, alkalosis,
kaliuresis; suppressed renin w/
severe HTN, hypokalemia, high aldosterone
alkalosis, low renin, hi
Renin nl converts
aldosterone
angiotensinogen to angiotensin
I; ACE converts angI to angII;
angII stimulates the adrenals to
secrete aldosterone;
aldosterone increases sodium
retention and potassium
excretion
Glucocorticoid
remedial
hyperaldoste
ronism
Etiologies
aldosterone
producing
adrenal
adenoma,
bilateral
adrenal
hyperplasia,
hypertensive
forms of CAH
(11B &17a
hydroxlase
def), adrenal
cancers
Deoxycortic
osterone
HTN
Epi
2-15%
prevalence
Risk factors
Lab/Imaging
aldosterone:renin ratio
(nl<20; >20 suggests
autonomous prod of
aldosterone)
confirm hyperald w/ oral salt
loading --> should shut down
aldosterone (if not
suppressed, suggests
autonomous prod of ald)
RARE: <1%
of hyperald
cases
CT scan of abdomen
bilateral adrenal vein
sampling (aldo:cortisol > 4
suggests adenoma)
FH hemorrhagic genetic testing for GRA
stroke (uncont
mutation on all pts w/ history
HTN)
of hyperald, strokes at young
age, or onset of HTN at young
age
Treatment
adenoma? Surgery
(curative)
medical mgmt?
aldactone, epleronone,
amilioride (K+ sparing)
deoxycorticosterone is made in
the zona fasciculata in response
to ACTH; elevated levels of
deoxycorticosterone seen in
adrenomas, adrenal
carcinomas, or CAH
thus, this MC is able to
contribute to HTN
Liddle
syndrome
autosomal
severe HTN, hypokalemia, mutation in gamma or beta
subunits of amilioride sensitive dominant
low aldosterone & low
renal sodium epithelial channels mutation
renin
in distal nephron --> ENaC
channels stay open longer
increasing Na reabsorption &
decreasing Na excretion
Syndrome of
Apparent
MC Excess
(AME)
BP control & tx of
hypokalemia
supression of cortisol w/
dexamethasone
spirinolactone
kidney transplant
Complications
Disease
Clinical
Variants
Licorice
Virilizing
syndromes
Sexual pain
disorders
Dyspareunia
Defining Characteristics
Pathogenesis
recurrent or persistent
involuntary genital pain
associated w/ sexual
intercourse
recurrent or persistent
involuntary spasm/
contraction of muscles
surrounding introitus prevent
penile insertion -> personal
distress;
Hypoactive
sexual
desire
disorder
(HSDD)
persistent or recurrent
deficiency or absence of
sexual fantasies and
desire for sexual activity
Epi
Risk factors
persistent or recurrent
extreme aversion to, and
avoidance of, all genital
sexual contact w/
appropriate sexual
partner
Lab/Imaging
Treatment
stop offending agent & BP
reverts to normal
Sexual desire
disorders
Etiologies
vulvo/
vestibulodynia
=
hypersensitivity
to yeast,
allergic
response,
HPV, genital
rash, autoimm,
estrogen def
vulvodynia =
most common
cause of
dyspareunia
inf = HSV,
HPV, GC, CT,
PID, UTI, BV,
trich,
candidiasis
menopause
(natural or
surgical)
meds (OCPs,
SSRIs - inhibit
pleasure
pathways)
tx infections
childhood
trauma
vaginal dilators,
psychogenic therapy,
muscle relaxatants
menopause,
OCP side
effect??
Complications
Disease
Clinical
Variants
Sexual arousal
disorder
Defining Characteristics
persistent or recurrent
inability to attain or
maintain an adequate
lubrication - swelling
response of sexual
excitement
Pathogenesis
Etiologies
arousal is mediated by
relaxation of arteriolar
smooth muscles (NO, VIP
mediated) in genitals that
increases blood flow into
clitoris and vaginal epithelium
Epi
Risk factors
Lab/Imaging
Treatment
possible female use for
PDE-5 inhibitors
(Sildenafil, tadalafil) to
prevent the breakdown
of cGMP
organic - DM,
Dysfxn? Inadequate afferent PVD, metabolic
syndrome,
and/or efferent neural
obesity
transmission to sexual
organs (psychogenic or
organic) OR inadequate
response of erectile & vaginal
tissue (insufficient release of
NO or VIP; downregulated
smooth muscle receptors;
insufficient second messenger
regulation of relaxation)
Orgasmic
disorder
Female
Orgasmic
Disorder
persistent or recurrent
delay or absence of
organsm following nl sexual
excitement phase
directed masturbation
program (if lifelong d/o),
relationship therapy (if
situational d/o),
Paratesticular
disorders
Hydrocele
painless enlargement of
scrotum that
transilluminates
lymphatic obstruction
congenital or
acquired
most common
cause of
scrotal
enlargement
usually 1st
year of life congenital
more
common
prior surgery,
neoplasm/ inf of
testis/
epididymis,
trauma
Complications
Disease
Clinical
Variants
Varicocele
Defining Characteristics
painless dilation &
tortousity of veins
Pathogenesis
Etiologies
Epi
Risk factors
10% of young
adults
Lab/Imaging
Treatment
cyst formation in
epididymis
hard, pea-sized nodules
above the testis
inflammation of
epididymis
Epididymitis
Testicular
torsion
Cryptorchidism
most
common
intrascrotal
inflamm d/o
untreated gonococcal
epididymitis -->
epididymis abscess
spread to testicles
infertility if chronic
scarring &
obstruction
2nd decade of
life
surgery to manually
untwist spermatic cord
minor injury?
testicular infarction /
necrosis if not
surgically managed in
time!
Bilateral risk so
gubernaculum is
fixed on both testes
anomaly of testicular
suspension - gubernaculum
attached horizontally instead of
at the bottom of the testis
usually arrested along the
inguinal canal (dangerous bc
this area is injury prone),
sometimes the top of the
scrotum, and even less
commonly the abdomen
Complications
3% of male
infants at birth
histology: atrophy of
orchiopexy
cryptorchid testis after 2y w.o
treatment; fibrosis of
seminiferous tubules
Orchitis
Bacterial
inflammation of testis
Syphilitic
inflammation of testis
Disease
Infertility
Male infertility
Clinical
Variants
Mumps
orchitis
Defining Characteristics
Supratesticular
Pathogenesis
Etiologies
Risk factors
Lab/Imaging
1/12 couples
35% - male
factor, 35% tubal factor;
15%ovulatory
dysfxn, 5%cervical
factor; 10%
unexplained
scar tissue
(Asherman's),
submucosal
fibroids, uterine
anomaly,
endometriosis,
PCOS,
Kallman's
syndrome, CF,
renal agenesis,
Klinefelters,
Turner
syndrome
sperm analysis
(oligospermia, immotile
sperm), ovulation detection
(basal body temp chart, urine
LH surge, endometrial bx, mid
luteal serum progesterone
>3ng/mL), eval anovulation
(preg test, FSH/LH, OCPs,
prolactin, TSH, androgens,
Cushings, acromegaly, CAH),
eval tubal/ uterine/
peritoneal factors
(hysteroscopy,
hysterosalpingogram,
laparoscopy); ovarian
reserve testing (Day3 FSH &
estradiol, clomiphene
challenge, inhibin B, AMH,
antral follicle count)
histology: anatomic
seminiferous tubules but no
active spermatogenesis;
Leydig cells are
indistinguishable from
stromal cells
no gonadotropins
varicocele
cryptorchid
testis w/
scarring
Klinefelters
idiopathic
obstruction of excretory
ducts, particularly the
epididymis
untreated
epididymitis
trauma
results in no spermatozoa in
the ejaculate, despite being
made properly in the testis
vasectomy
most common
cause
Complications
fertility usually
preserved in
unilateral infections
result in immature
seminiferous tubules - no
signs of spermatocyte
differentation (resemble those
of prepubertal testes), or
decreased spermatogenesis
Testicular
Treatment
mumps
30% of postchildhood virus pubertal
males w/
mumps
Oligospermia: exogenous
testosterone- dec
spermatogenesis from inh of
LH/FSH; lack of GnRH neuronsKallman's syndrome; congenital
bilateral absence of vas
deferens - CF, abnl
mesonephric duct diff;
Klinefelters - low testosterone,
elev FSH
immotile sperm: primary ciliary
dyskinisia - Kartagener
syndrome
drugs: CCBs
ovulatory dysfxn: anovulation
(PCOS, androgen excess, low
gonadotropins, hi prolactin,
diminished ovarian reserve,
primary ovarian insuff,
hypothyroidism
tubal/uterine dz: PID,
appendectomy, TB, DES exp,
hydrosalpinges, endometriosis
Ovarian reserve:
problems with hypothalamus GnRH; pituitary gland - lack of
gonadotropins; systemic
diseases that suppress
spermatogenesis (those a/w
fever)
Epi
histology: IDIOPATHIC?
Germ cell maturation arrest,
germ cell aplasia (Sertoli
cells only, no germ cells)
Disease
Clinical
Variants
Hypogonadism (general)
Defining Characteristics
Pathogenesis
pre-pubertal = small
testes, eunuchoidal
skeletal proportions, hi
pitched voice, dec muscle
mass, delayed bone age,
dec body hair
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
check morning testosterone start tx around 12y.o. (low watch out for
levels, LH & FSH, prolactin, doses then dose hi and
inappropriately
every 2weeks)
semen analysis
normal
gonadotropins!! (if
testosterone
cranial imaging, bone age,
low testosterone,
replacement - IM q 2w,
U/S of scrotum & adrenals,
would expect to have
neuro exam (visual fields skin gels/ patch (cannot hi FSH/LH - suspect
R/O pituitary lesions),
be given as pill bc
pituitary/
testicular size, karyotype,
dangerous to liver!)
hypothalamus
med hx (anabolic steroids?),
pathology)
trauma (testicular or head)
check other pituitary
hormones and adrenals!
Disease
Gonadal
dysgenesis
Clinical
Variants
Defining Characteristics
congenital
hypergonadotropic
hypogonadism
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Klinefelter's
Syndrome
congenital
hypergonadotropic
hypogonadism from
gonadal dysgenesis
1:10,000
prisoners
Sertoli Cell
Only Syndrome
congenital
hypergonadotropic
hypogonadism
male
pseudohermaphroditism
congenital
hypergonadotropic
hypogonadism
Vanishing
Testes
Syndrome
Septo-optic
dysplasia
congenital
hypergonadotropic
hypogonadism
congenital
hypogonadotrophic
hypogonadism
autosomal
recessive
mutations of
LH receptor
NO seminiferous tubules or
sperm!
congenital
hypogonadotrophic
hypogonadism
HYPOSMIA OR ANOSMIA
(loss of smell) a/w
hypogonadism bc same
anatomic location as
olfactory bulb
1:10,000
M>F 5:1
Treatment
Complications
Disease
Hypergonadism
Clinical
Variants
(general)
Defining Characteristics
androgen excess, acne,
virilization, anger, small
testes
Pathogenesis
early pubertal development
from excessive androgen
secretion
Etiologies
Epi
Risk factors
Lab/Imaging
anabolic
steroids
Treatment
treat cause
Complications
often also have low
HDL so at risk for CVD
inhibit testosterone w/
GC (if adrenal cause),
surgery (if tumor), or
discontinuation of meds
(if exogenous anabolic
steroids)
endogenous (central
precocious puberty, adrenal
gland abnormality, androgen
secreting tumor)
exogenous (anabolic steroids)
Menopause
natural
occurs
around age
50
early
menopause?
Smoking,
surgery,
genetics,
radiation/ chemo
exp,
autoimmune,
med induced
(Lupron)
treatment only if
symptoms impact QoL;
use lowest effective dose
of HRT; can also use
transdermal / transvag
admin of HT to reduce
blood clot risk
Premature
Primary ovarian
insufficiency
idiopathic
(maj), Turners
syndrome,
chemotherapy,
familial, pelvic
surgery,
gonadal
dysgenesis
(46XY),
galactosemia,
pelvic
irradiation
premature or
primary
ovarian insuff
occurs <40
1% of women
endometrial
hyperplasia & cancer if
continuous estrogen
exposure w/o enough
progesterone in
perimenopausal
women
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
Screening /
Education
daily glucose
monitoring,
realistic BG
targets, healthy
lifestyle (diet,
ex), office visits
q 3-4m for
evaluation of
retina, lower
extremities, CV,
& routine
screening (A1C,
TFTs, lipids)
Prevention 1.autoimm
2. prevent dz in
those w/
autoimm
3. intervene to
preserve islet
cells
OGTT = most
sens way to dx
pre-diabetes or
diabetes (post
prand gluc rises
first)
gluc monitoring
& self-mgmt of
insulin
adjustments for
stress, ex,
sickness, diet
CVD risk factors
and
complications
screening
Screening /
Education
A1s are at low
risk for IU
demise; do not
need
antepartum
surveillance or
early elective
induction
A2s: antenatal
surveillance w/
US & NST at 32
weeks until
delivery,
2x/week
PP: screen 612 wks w/ 75g
2h OGTT (DM if
FBS >126, 2h >
200)
pre-preg ex a/w
lower GDM risk
prevent w/ early
INTENSIVE
glucose control
Screening /
Education
Screening /
Education
every patient
over age 60
should have
TSH checked!
Increase
levothyroxine
dose by 30% in
pregnant
patients!!
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
recurrent
parathyroid dz
possible
Screening /
Education
Screening /
Education
Screening /
Education
rarely malignant
dopamine
agonists limited
during
pregnancy (no
progression of
microadenoma
during
pregnancy
despite
estrogen
stimulation)
surgical
debulking of
macroadenomas prior
to pregnancy bc
can worsen
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
routine
evaluation?
Cardiovasc
screen,
anticipatory
mgmt for aortic
dissection,
thyroid function,
celiac screen,
FSH/LH, renal
& liver fxn,
DEXA, psych
consults, blood
glucose/ fasting
lipids, ENT/
audiology
Screening /
Education
Screening /
Education
Screening /
Education
expectant
management &
reassurance
Screening /
Education
Stages:
I - ovaries only
II - pelvis,
ovaries
III - abdomen,
lymph nodes,
superficial liver
IV - outside of
abdomen,
parenchymal
liver
lower survival
w/ higher stage
Screening /
Education
yearly paps
beginning ages
21-29; if lowrisk, paps every
2-3yrs after age
30 if 3 normals
in a row
stop paps at
70y.o. if no abnl
in last 10 years
& 3nls in a row
stop paps if
hysterectomy &
no h/o CIN2/3
Screening /
Education
Screening /
Education
continue to
monitor other
testicle if prior
germ cell tumor!
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
yearly
mammograms
for women >
age 40
breast exams q
3y for women
20-40; yearly
age > 40
hi risk women yearly MRI of
breasts
Screening /
Education
Screening /
Education
female
screening- CT
(sex active <24;
at risk >25),
gonorrhea /
HIV/syphilis (at
risk), cervical
Ca (all sex
active women
w/ cervix)
pregnant
women - CT if
at risk or less
<24; syphilis,
HepB
MSM - yearly if
sex active:
syphilis, HIV,
GC/CT, hep;
selective males
screen women
< 25 for
chlamydia!
Screening /
Education
PROTECTIVE
SEX!!
Gardisal
quadrivalent
vaccine
Chlamydia =
leading
preventable
cause of tubal
factor infertility
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
check testes
regularly to
screen for
development of
neoplasms,
even after
orchiopexy!
Screening /
Education
Pre-implantation
genetic
diagnosis
(PGD) aneuploidy
screen, single
gene defect,
HLA matching,
sex selection
Screening /
Education
Screening /
Education
Screening /
Education
CVD &
osteoporosis
screening
Screening /
Education
Screening /
Education
Disease
Clinical
Variants
Aplastic anemia
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
sometimes
immunosuppression helps
restore cell lines
Complications
infections - unable to
generate new
lymphocytes
(general)
inappropriate absolute
JAK2 mutation
polycythemia (EPO independent
colony growth) from mutation in
JAK2/STAT pathway -->
upregulated transcription of
lineage specific myeloid genes
for WBCs, RBCs, platelets
(basically myeloid cell line
expansion)
eradicated Philadelphia
can progress to AML
chromosome (causative
(blastic phase)
agent), prevent progression
to blast phase (AML)
mean survival of chronic
phase = 4-6y
targeted therapy against
resistance to Imatinib by
BCR-ABL via tyrosine
kinase inhibitors (Imatinib/ cancer cells (pump drug
out of cell, produce
Gleevec, Dasatinib,
more BCR-ABL, develop
Nilotinib)
mutations to prevent
Allogeneic HSCT if resistant drug MOA)
to imatinib
Disease
Clinical
Variants
Defining Characteristics
Primary
anemia, splenomegaly,
myelofibrosis elevated or decreased WBC
& platelets
portal hypertension
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
Myelo-dysplastic Refractory
subacute presentation
syndromes
anemia (w/ or ("feeling bad") w/ anemia +/(MDS)
w/o ringed
neutropenia,
sideroblasts) thrombocytopenia (1, 2, 3
cell lines affected)
refractory
anemia w/
anemia, bleeding,
multilineage infections
dysplasia
refractory
anemia w/
excess blasts
prior chemo/
more
common in radiation
treatment
elderly
frequently progresses
to AML (30% of cases)
Prognosis depends on
proportion of blasts in
bone marrow,
cytogenetic features,
& number of
cytopenias
5q syndrome
Acute
myelogenous
leukemia (AML)
completely immunodeficient
(pancytopenia)
Primary:
exposure to
chemicals
(benzene shoes, rubber),
radiation,
hereditary
(Fanconi's,
Down's)
Secondary:
chemotherapy,
hematologic dz
(CML, MDS)
1/150,000
bimodal age
distribution
(15-59)
poor cytogenics or
normal cytogenics but
poor mutational risk
profile - do not survive
beyond 2 years &
require transplant!
Worse survival out of
the leukemias
hyperleukocytosis -->
CNS injury & pulm
leukostasis
Disease
Acute
lymphocytic
leukemia (ALL)
Chronic
lymphocytic
leukemia (CLL)
Clinical
Variants
Defining Characteristics
Etiologies
lymphadenopathy +
elevated WBC/ ALC
precursor to CLL
stem cell gives rise to slightly more genetic mature lymphoid progenitor cell
sensitivity to B
that proliferates out of control
cell hypersensitization (FH
of autoimmune
genetic & environmental
dz)
combination of etiologies
Epi
Risk factors
higher SES,
Down's
syndrome,
radiation
exposure, late
2.8/100,000 common
S/S: anemia (dec energy,
infections, FH
CHF), thrombocytopenia
environmental - 2-3y.o.
of
(hemorrhage - mucosal;
lack of pathogen exposure as an
lack of exposure (peak
autoimmune
petechiae, bruising),
infant, with subsequent delayed
exposure to pathogens at time of to pathogens in incidence) dz
leukopenia (infxn, fever),
M>F slightly
increased lymphoid proliferation -- infancy
systemic involvement
(fever, weight loss, malaise, > extremely robust response
others - trisomy
decreased activity),
21, high birth
extramedullary involvement
rate, ionizing
(lymphadenopathy, hepatoradiation, "late"
splenomegaly, bone/ joint
common inf,
pain- bilateral; CNS sx topo-isomerase
chloromas, leukemic
II inhibiters
meningitis, renal failure,
edema, skin or testicular
masses)
infections - decreased
polyclonal immunoglobulins
Monoclonal Bcell
Lymphocytosis
Pathogenesis
most
common
childhood
malignancy
3/100,000
per yr
most
common
overall
leukemia &
most
common
cause of
general
lymphadenopathy
in adult >
60
MBL
(monoclonal B
cell
Caucasian> lymphocytosis
AA>Asian
)
patients >
age 60
6-15% of
age
relatives of (increased
CLL patients CLL clones)
Lab/Imaging
Treatment
important to observe
asymptomatic patients!!
use of maintenance tx
(administer low dose drugs
1.5-2.5y) - hallmark of ALL
Complications
CNS prophylaxis
Richter's transformation
(1% per year) - evolve
into large cell lymphoma
1.2-1.4% of MBL
becomes CLL
Disease
Clinical
Variants
Plasma Cell
Myeloma
Defining Characteristics
Pathogenesis
Etiologies
MGUS
precursor to myeloma!!!
Evan's syndrome
autoimmune hemolytic
anemia + ITP
Lymphomas
median age
66y.o.
Risk factors
Lab/Imaging
Treatment
Complications
autologous transplant
incurable!
Thalidomide,
lenalidomide, bortezomib
most impt for remission
rates & improved
outcomes
Staged by Beta-2
microglobulin (total body
burden of plasma cells)
& albumin; cytogenetics
for high risk mutations
(general)
4.3/100,000
AA>
Caucasians
Monoclonal
Gammopathy of
Undetermined
Significance
(MGUS)
Epi
Disease
Clinical
Variants
Hodgkin's
lymphoma
Defining Characteristics
asymmetric
lymphadenopathy (90% of
cases - firm, rubbery, motile;
supraclavicular, lower
cervical), rare
hepatosplenomegaly,
extranodal manifestations
(rare except in HIV+ or
advanced stage), B
symptoms (1/3 of cases),
painful lymph node when
drinking alcohol
Pathogenesis
Etiologies
contiguous LN involvement
suggests spread via lymphatic
system
Epi
Risk factors
bimodal
age
distribution
(15-34; >50)
later exposure
to EBV, HIV,
iatrogenic
immunosupp
, higher SES
Lab/Imaging
Treatment
Complications
w/ treatment, 5y
survival: Stage 1- 90%,
Stage 2- ~90%, Stage 3 85%, Stage 4- 75%
no treatment - death!!
(mass effect, immune
dysreg, profound
anemia)
NonHodgkin's
lymphoma
Fever
neutropenia
Low risk
spreads hematologically so
random lymphadenopathy
HIV a/w
increased
Burkitt's
lymphomas,
very
aggressive
plasmablastic
indolent - usually present as
lymphomas,
diffuse lymphadenopathy & follicular lymphomas usually
aggressive
have translocation 14;18 (moves diffuse large B
involve the BM
Ig heavy chain next to Bcl-2 =
cell lymphomas
marked overexpression of Bcl2 =
hepC a/w splenic marginal
zone lymphoma; H. pylori a/w anti-apoptotic)
MALToma - both respond to
Burkitt lymphoma - B cell
tx of infectious agent
neoplasm w/ translocation 8;14
mycosis fungoidies - mature places heavy chain next to cMyc oncogene; endemic (Africa)
T cell lymphoma -->
disfiguring skin lesions -->
forms a/w jaw swelling & EBV;
Sezary syndrome (end
non-endemic (a/w HIV, EBV
stage)
negative)
Solid tumors, ALL/NHL in
GN bacteremia from enteric
remission, neutropenia <
source (Pseudomonas)
7days, expected neutropenia
< 10days, no localization
indolent / low grade - dec
apoptosis; aggressive /
intermediate grade - dec
apoptosis, slightly inc mitosis; very
aggressive / high grade - dec
apoptosis, VERY inc mitosis
most
common
type of
lymphoma;
4% of new
malignancie
s, rising
incidence
Burkitt
lymphoma peaks in
kids age 11;
adults at
age > 30 fastest
growing
malignancy
!!
age (50-60
y.o.),
environment
al exposure
(chemicals fertilizer,
pesticides,
solvents),
chemotherap
y, radiation,
immune
suppression,
HIV/AIDS,
autoimmune
dz (Sjogrens,
Hashimotos,
RA, Celiac),
infectious
(HTLV1, EBV,
human
herpes virus
8, hepC,
H.pylori)
CHOPR =
Cyclophosphamide, hydroxy
doxirubicin, oncovin
(Vincristine), prednisone,
rituximab
If relapse, HSCT - 50% can
be cured if respond to
salvage + transplant
recommend observing
indolent NHL like follicular
lymphoma if
asymptomatic; once
symptomatic, use rituximab
determine prognosis via IPI = (improves lifespan)
inc risk is age > 60,
performance status 2-4,
elevated LDH, extranodal
involvement, Ann Arbor stage 34
BM bx: not std of care, but if
abnl lymphocytes automatically
stage IV disease
secondary
malignancies, CAD
Ann Arbor staging:
Stage 1 = single LN
region; Stage 2 = 2 LN
regions on same side of
diaphragm; Stage 3 =
LNs on both sides of
diaphragm; Stage 4 =
diffuse/ dissem involv of
extralymphatic organ
Indolent - survival mos yrs w/o tx; observation
after chemo; incurable
aggressive - survival
wks - mos w/o tx; combo
chemo outpt; >50% cure
rate
very aggressive survival days to weeks;
combo chemo inpt; cure
rate >50%
3% follicular
lymphomas transform
to aggressive forms
Fever
neutropenia
Disease
Clinical
Variants
High risk
Defining Characteristics
Pathogenesis
GN bacteremia (Pseudomonas),
GP bacteremia (Staph, Strep)
abdominal symptoms present?
GN bacteremia (Pseudomonas),
GP bacteremia (Staph, Strep), or
Anaerobes
unstable? Tachycardia,
hypotension, respiratory
distress
Etiologies
Epi
Risk factors
Lab/Imaging
GN enterics,
Staph/ Strep,
Anaerobes
GN bacteremia: ceftazadime
other sources?
HSV, varicella,
dysphagia
(fungal, CMV,
HSV), yeasts/
molds
abdominal symptoms:
meropenum (anaerobes,
Pseudo), vancomycin, +/tobramycin
Tumor lysis
syndrome
Complications
GP bacteremia: vancomycin
unstable: meropenum,
vancomycin, amikacin
(double coverage against
pseudo)
Typhlitis
Treatment
BSA
management of
constipation/ diarrhea
monitor coags
pain mgmt, nutrition
IV fluids + urate oxidase +
hyperkalemia,
IV calcium gluconade/
hyperphosphatemia,
hypocalcemia, hyperuricemia chloride if seizure/ heart
failure + amphogel +
treatments for hyperkalemia
hypocalcemia -->
muscle spasm, heart
failure, seizures
hyperuricemia &
hyperphosphatemia -> renal failure
hyperkalemia -->
arrhythmias (sine wave,
Torsaud's)
Disease
Mediastinal
mass
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
CXR!!
Treatment
sedation is
contraindicated!!
Spinal cord
compression
Thrombocytopenia
3-5% of
newly
diagnosed
oncology
patients
platelets <150K
Normal WBC & Hb? Check
peripheral smear
- nl RBC morphology, platelets
nl or increased in size consider drug induced, ITP,
infection induced, congenital
thrombocytopenia
- fragmented RBCs - consider
hemolytic anemias (DIC, TTP)
- clumped platelets - redraw in
sodium citrate or heparin
Abnl Hb & WBC? - bone
marrow exam
1.54/100,000
per year
avg age 2050
Complications
Disease
Clinical
Variants
Heparin-induced
thrombocytopenia (HIT)
Defining Characteristics
Pathogenesis
Drug induced
thrombocytopenia
Platelet
sequestration
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
requires IMMEDIATE
thrombotic events!!
discontinuation of heparin
& use of alternative anti- Life & limb threatening
coagulation therapy!!
condition
Treat thromboembolic event
continue anti-coagulation
after d/c from hospital thrombosis risk remains
thrombocytopenia
Dilutional
thrombocytopenia
Thalassemias
(general)
Alpha
Hb Electrophoresis: HbH
Iron studies: normal ferritin
Smear: target cells,
microcytic, HbH inclusions
CBC: mild anemia + significant
microcytosis = alpha thal
minor; low normal MCV but
hematologically normal = alpha
thal carrier
Complications
Disease
Clinical
Variants
Beta
Defining Characteristics
Hypoproliferative
anemias
(general)
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
decreased production of
hemoglobin/ RBCs
Microcytic, normocytic, or
macrocytic (see below)
Microcytic
anemias
(general)
Iron
deficiency
anemia
Treatment
inadequate iron
supply
(deficiency or
not free for
utilization), abnl
globin synthesis,
abnl assembly of
porphyrin ring
inc blood loss
(GI - colon Ca,
excessive
menstruation),
dec iron intake
(diet, iron
malabsorp), inc
requirements
(pregnancy,
lactation),
unknown
Smear: microcytic
hypochromic RBCs
Iron studies: low serum iron, inc
TIBC, dec % sat, dec serum
ferritin
Complications
hemochromatosis (iron
overload following blood
transfusions) - require
iron chelating agents
cardiac dz, GI dz, & DM
(from iron deposition on
other organs)
Disease
Clinical
Variants
Defining Characteristics
Anemia of
chronic
disease
(ACD)
Pathogenesis
Normocytic
anemias
(general)
Metabolic
Etiologies
Epi
chronic
infections (TB,
abscess,
syphilis),
neoplasms,
chronic
inflammation
(arthritis, RA,
gout)
2nd most
common
cause of
anemia,
hospitalize
d patients!
Lab/Imaging
most
endemic
high RBC & low Hb or low
common
malaria areas MCH
monogeneti
c d/o
worldwide
inherited defects
Smear: dimorphic picture
(normal RBCs+ hypochromic
secondary
microcytic cells)
defects - preBM bx: ringed sideroblasts
leukemia,
(rings around nucleus & iron in
drugs (INH),
mitochondria)
alcohol, lead
CBC: high RDW
poisoning
Iron studies: high iron, nl TIBC,
high ferritin
Pregnancy
pregnancy = pseudoanemia;
dilutional - hormones secreted
cause plasma expansion, causing renal failure
measured hemoglobin to be
slightly low
renal failure = lower limit of
creatinine clearance indicates
severe kidney disease, resulting in
less EPO production, thus less
RBC & Hb production; EPO
deficiency, shortened RBC
survival, nutritional deficiency
w/ dialysis
Risk factors
Treatment
Complications
Disease
Clinical
Variants
Defining Characteristics
Endocrine
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
androgen
deficiency
hypothyroidism
adrenal failure
Hypothyroidism = reduced
thyroid hormone causes reduced
metabolic rate & decreased need
for O2 (thus Hb)
adrenal failure = corticosteroid
deficiency causes anemia
Macrocytic
anemias
Marrow
replacement
infections,
tumors, scar
tissue
Marrow
failure
aplastic anemia
leukemia
Anemia of
chronic
disease
(ACD)
initially presents as
normocytic anemia (as
disease progresses, it
becomes microcytic anemia)
(general)
high
reticulocyte
count
Target cells
Severe hypothyroidism
Treatment
Complications
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
Acquired
hemolytic
anemias
(general)
Splenomegaly
Etiologies
vitB12
deficiency,
folate
deficiency,
chemotherapy,
myelodysplastic
syndromes,
hereditary
defects in DNA
synthesis
B12D = vegans,
absorption probs
(low pancreatic
enzymes,
pernicious
anemia, small
bowel dz Celiacs,
Crohns), liver
dz, fish
tapeworm
Epi
Risk factors
FH of
autoimmune
dz (B12d)
Lab/Imaging
Treatment
Complications
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
Other
acquired extrinsic RBC
abnormalities defect resulting in noncausing
immune mediated hemolysis
acquired, nonimmune
mediated
Etiologies
valvular/
vascular
prosthesis,
severe AS, DIC,
vasculitis, RA,
SLE, TTP, HUS,
hemangiomas,
eclampsia,
malignant
hypertension,
pulm HTN
Epi
Risk factors
systemic
illness
Lab/Imaging
Treatment
Complications
Smear: schistocytes
Alloimmune
hemolytic
anemia
transfusion
acute transfusion reaction major blood group incompatibility -- reactions
> preformed antibodies to RBCs;
when transfused w/ these RBCs,
the Hb goes up but then
immediately falls (hemolysis)
Smear: microspherocytes +
increased reticulocytes, cold
antibody AIHA has prominent
agglutination or clumping of
RBCs
Coomb's test: Warm antibody
(IgG or IgG+complement),
Cold antibody (Complement
only)
Disease
Inherited
hemolytic
anemias
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
(general)
gallstones? Increased Hb
breakdown = inc indirect bili = inc
bile salts = inc pigmented
gallstones --> cholecystectomy
Epi
Risk factors
Lab/Imaging
Treatment
Hereditary
spherocytosis
Smear: microspherocytes,
splenectomy helps with
elevated retic count (looks just symptoms but morphological
changes persist
like AIHA so need Coomb's
test to R/O)
Hereditary
elliptocytosis
Hereditary
pyropoikilocytosis
autosomal
dominant
autosomal
recessive
Complications
Disease
Clinical
Variants
Sickle cell
disease
G6PD
deficiency
Transfusion
associated
GvHD
Transfusion
reactions
Defining Characteristics
Pathogenesis
hemolytic anemia
increased severity of
infections (s. pneumo,
meningitis)
tissue infarction w/ organ
failure (leg ulcers, stroke,
nephropathy)
severe pain episodes (bone
degeneration from sickling -->
arthritic pain & loss of
function; sudden onset pain in
extremities & back)
occurs if immunocompromised
patients receive blood that is not
irradiated!!
Acute
hemolytic
transfusion
rxn
skin sloughing
often due to ABO
incompatability, most likely
due to clerical error (misidentification of patient)
Etiologies
a.a.
substitutions,
deletions, or
insertions
resulting in
G6PD instability,
In G6PD def, there is inadeq
defective
NADPH so Hb and proteins
become oxidized and precipitate enzyme fxn, or
in RBC --> inclusions of Hb that combos
bind RBC membrane (Heinz
bodies)
intravascular hemolysis,
complement mediated, IgM
Risk factors
8-10% of
African
Americans
Lab/Imaging
pain is the
most
severe
complicatio
n
(disability,
healthcare
$)
Treatment
hydroxyurea - increases
production of HbF to
interfere w/ sickle cell
polymerization & reduce
frequency of sickle events
Complications
7-8% of
African
Americans,
10-15% of
Mediterrane
an heritage
severely
immunocompromise
d; neonates
STOP transfusion!!
Flush w/ IVF
Check CBC to monitor
platelets & Hb, check renal
fxn labs and coagulation
studies
Epi
ARF, DIC
Disease
Clinical
Variants
Febrile
reaction
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
STOP transfusion!!
cannot be distinguished
from fever in acute
hemolytic rxn so
transfusion must be
stopped!!
Septic
reaction
Urticarial
reactions
Tranfusion
fluid overload --> breathing
associated
problems
circulatory
overload
(TACO)
Iron overload liver/ cardiac/ endocrine
problems
consider IgA
deficiency!
Aspergillosis
3% of
transfusions
(second
most
common
reaction)
#1 leading
cause of
death from
transfusion
antihistamine, epinephrine,
steroids, supportive care
improves w/ diuretics
(UNLIKE TRALI!)
Complications
Disease
Clinical
Variants
Mucormycosis
Defining Characteristics
Pathogenesis
Candidiasis
Qualitative
(general)
platelet disorders
Etiologies
Epi
low
incidence
(1.7/100K)
Risk factors
Lab/Imaging
Treatment
neutropenia,
immunocomp
(HSCT, organ
transplant,
cancer,
autoimmune
dz), poorly
controlled DM
bloodstream
infxn risk
factors?
Neutropenia,
indwelling
devices,
hemodialysis,
DM, AIDS,
abd surgery,
critical illness,
neonate,
age>65, TPN,
broad
spectrum Abs
DDAVP - synthetic
derivative of
ADH/vasopressin so causes
release of VWF from
endothelium (increases
stickiness of plasma)
anti-fibrinolytic agents block
plasmin and prevent lysis of
fibrin within clots
COX1
inhibitors
aspirin, NSAIDs
bruising, bleeding
Clopidogrel
(Plavix)
Uremia (renal
dysfxn)
Complications
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
Glanzmann
thrombasthenia
absence or dysfunction of
integrin aIIbB3, preventing
platelet aggregation
BernardSoulier
syndrome
thrombocytopenia w/ giant
platelets
absence or dysfunction of
platelet adhesive receptor
(GP1b), preventing platelet
adhesion
dense granule def - patients will
also have varying degrees of
albinism
Absence of
platelet
granules
Etiologies
mutation within
the binding site
of aIIbB3 or talin
deficiency (talin
nl exposes
binding site)
Epi
Risk factors
Lab/Imaging
Treatment
von Willebrand
disease (VWD)
Dysfunctional
granule
release
(general)
VWF activity less than 30% certain conditions can also change autosomal
the amount of circulating vWF; ie dominant
= increased bleeding risk
sympathetic response has
increased vWF in preparation for
injury
hi vWF - stress, exercise,
pregnancy, age, acute & chronic
inflamm, DM, OCP use,
malignancy, hyperthyroidism
Type 1 (7580%)
Type 3 (13%)
Type 2
normal VWF levels but
(qualititative; decreased VWF activity
15-20%)
from:
1. decreased multimers
circulating
2. decreased binding to
factor GP1b
3. abnl binding to factor 8
4. dysfxnal hi affinity
interaction w/ GP1b
Complications
Disease
Inherited
hemophilia
Clinical
Variants
Defining Characteristics
Hemophilia A = factor 8
deficiency
Hemophilia B = factor 9
deficiency
Pathogenesis
Etiologies
X-linked
20-30% =
spontaneous
mutations
Epi
Risk factors
Lab/Imaging
Treatment
A = 1/10K
male births
B = 1/30K
male births
Complications
Acquired
hemophilia
Lupus
anticoagulant
thrombosis
Vitamin K
deficiency
Liver failure
control bleeding
eradicate inhibitor w/
steroids, IVIG, rituximab
infancy,
malabsorption,
hyperemesis
gravidarum,
fasting,
alcoholism,
drugs
(warfarin, Abs,
salicylates)
intercerebral, GI,
prolonged PT, prolonged PTT, asymptomatic? Oral or IM
vitK
umbilical, or ENT
post mixing study corrects
bleeding
PTT
active bleed? Emergency!
Requires FFP then correct
vitK
autosomal
recessive
abnl PTT
Factor 12
deficiency
Hageman factor
NOT a/w bleeding
NO TREATMENT!!
Disease
Fibrinogen
abnormalities
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
increased fibrinogen? Acute prevents stable formation of crossphase reactant, inflammation, linked fibrin clot OR
overproduction of fibrin clots
pregnancy
Epi
Risk factors
Lab/Imaging
Treatment
acquired? Supportive tx
only
Atypical? Poor prognosis
w/ renal failure; cannot be
transplanted (intrinsic dz)
Disseminated
Intravascular
Coagulation
(DIC)
Acquired - Ab
formed to
ADAMTS13
bleeding + subclinical or
clinical thrombosis
sepsis,
malignancy,
trauma/ head
injury/ burns,
obstetric
causes
(eclampsia,
retained fetus,
abruptio
placenta)
sepsis patients!
congenital - def
ADAMTS13
others? AA,
toxins,
transfusion,
immunologic
ELEVATED D-DIMER
cryoprecipitate to keep
fibrinogen elevated
platelet transfusions (keep
platelets > 50K)
??heparin
Complications
Disease
Venous
Thrombosis
Clinical
Variants
Defining Characteristics
(general)
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
immobilizati
on, burns,
HIT, DIC,
pregnancy
anticoagulation
continued if high risk of
recurrence (i.e. no
reason for VTE at time
of diagnosis unprovoked VTE, type
of underlying syndrome,
gender - men, elevated
D-dimer 1m after d/c
warfarin)
post-thrombotic
syndrome (see below)
persistent
risk factors?
Inherited
thrombophilia,
acquired
thrombophilia
s, obesity,
CHF,
nephrotic
syndrome,
Superficial
vein
thrombosis
(SVT)
Deep vein
thrombosis
(DVT)
Postthrombotic
syndrome
(PTS)
major risk of
embolization to lungs
(PE) and post
thrombotic syndrome
(PTS)
20-50% of
pts w/
symptomatic
proximal
vein DVT
common
femoral or
iliac vein DVT
regular use of
compression stockings!
(must be replaced every 6
months, worn daily for 2y
after DVT)
hi BMI
prior
ipsilateral
venous
thrombosis
female
older age
Anti-thrombin
deficiency
1% of pts
with VTE
1/250-1/500
prevalence
Disease
Clinical
Variants
Protein C
deficiency
Defining Characteristics
Protein S
deficiency
Pathogenesis
Factor V Leiden
Antiphospholipid
syndrome
(APS)
Epi
Risk factors
Lab/Imaging
2-9% of
patients w/
VTE
3% of pts w/
VTE
Acquired
thrombophilia
Etiologies
synergism w/ OCPs
enhanced platelet activation &
thrombosis (1+ episodes
confirmed by imaging/ path) subsequent aggregation
OR pregnancy morbidity
(recurrent pregnancy loss) enhanced TF expression thru
monocyte activation
PLUS
inhibition of protein C/S
anticoagulant pathway
high anti-B2
glycoprotein/high aCL
activation of complement
antibodies/ high Lupus
anticoagulant
Treatment
Complications
Screening /
Education
Screening /
Education
remission =
residual leukemia
burder below
level of detection
cure = remission
beyond 5 years
Screening /
Education
better prognosis
than AML
COG - children's
oncology group guarantees
clinical research
trial for every kid
w/ leukemia
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
newborn
screening = early
diagnosis &
prompt tx of
infxns & comps
informed
reproductive
decisions for
sickle traits
PCN
prophylaxis
birth to age 5
can be
prevented if
blood is
irradiated for at
risk patients!!
Screening /
Education
avoid transfusion
of plasma
containing
products; wash
products prior
to future
transfusion,
premedicate;
transfuse from
IgA def donors if
pt is IgA def
declining
incidence due to
use of male only
FFP
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
Compression
stockings
IVC filters if
contraind for
anticoagulation
Screening /
Education
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Subdural
hematoma
Epidural
hematoma
blow to skull
(baseball)
Treatment
Subarachnoid
hemorrhage,
intracranial
hemorrhage
Coup contra
coup injury
Brain herniation
Falx cerebri
Tentorium
cerebelli
(uncal
herniation)
Left (dominant)
hemisphere
lesion
ABCs, Neurosurgical
consult
Foramen
magnum
Hydrocephalus
decompressive surgery
Complications
Disease
Clinical
Variants
Defining Characteristics
Right
(nondominant)
hemisphere
lesion
Medial midbrain
syndrome
Lateral
medullary
syndrome
Pathogenesis
Etiologies
infarct to the
vertebral artery
or posterior
inferior
cerebellar artery
Horner's
syndrome
oculosympathetic pathway
projects from hypothalamus to
lateral tegmentum (MB, pons,
medulla) to the intermediolateral
cell column of the spinal cord;
interruption in this pathway causes
Horner's syndrome
lesion above
T1 (Pancoast
tumor, BrownSequard
syndrome, late
stage
syringomyelia)
Medial medullary
syndrome
contralateral weakness,
contralateral loss of fine
touch, ipsilateral tongue
weakness
infarct of
vertebral artery
or anterior
spinal artery
(posterior
circulation)
Bell's palsy
reactivation of
viral
inflammation of
facial nerve by
stress,
emotional
triggers??
Cerebellar
pontine angle
tumor
Epi
Complication of
AIDS, lyme dz,
HSV,
sarcoidosis,
tumors, DM
most
common
mononeuropathy
Risk factors
Lab/Imaging
Treatment
Complications
Disease
Basilar pontine
infarction
Clinical
Variants
Locked in
syndrome
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
(general)
1-2% of
population
2+ unprovoked seizures,
generalized or focal
PMH of
complex
febrile
seizures as a
kid, head
trauma,
alcoholism,
recreational
drug use,
encephalitis,
develop
delay, stroke,
focal brain
lesions
FH of
epilepsy
Idiopathic
(primary)
relatively self-limited,
medication responsive
considered
genetic
good prognosis,
resolves by teenage
years
Juvenile
Myoclonic
Epilepsy
normal development
myoclonic (muscle
twitching), GTC seizures
seizures can be
triggered by
EtOH or lack of
sleep
most
FH
common
idioathic
generalized
epilepsy
requires lifelong
treatment, medication
responsive
normal development
Benign
Epilepsy with
Centrotemporal
spikes
(BECTS)
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
LennoxGastaut
Syndrome
symptomatic (structural or
metabolic) generalized epilepsy
syndrome
Nocturnal
Frontal Lobe
Epilepsy
(NFLE)
mean age
of onset
14y (mostly
kids)
Carbamazepine or other
AED
Safe environment
70% men
Focal seizures
(general)
more
common in
adults
(acquire risk
factors;
complex
partial
seizures)
Disease
Clinical
Variants
Complex
partial
Defining Characteristics
loss of consciousness;
lasts 1-2m
Pathogenesis
focal seizure
automatisms (involuntary
non-purposeful behaviors: lip
smacking, repetitive arm
movements, eye blinking),
S&S can vary depending on
area of seizure activity
(aphasa if left temporal lobe,
often occur at night if frontal
lobe)
Etiologies
Epi
Risk factors
focal brain
lesion (tumor,
AVM, abscess,
old stroke, posttrauma, mesial
temporal
sclerosis, HIV
dementia,
Alzheimer's)
Lab/Imaging
Treatment
Complications
AEDs or if refractory to
multiple meds, surgical
resection
amnesia
Secondarily
generalized
tonic-clonic
Generalized
seizures
post-ictal confusion or
weakness
convulsive seizure
(general)
Tonic-clonic
Todd's paralysis
(transient, post-ictal
hemiparesis CL to
seizure focus)
more
common in
kids
most
common
type of
seizure
Absence
2nd most
common
seizure
kids
often misdiagnosed as
ADHD
Myoclonic
Clonic
Tonic
may progress to
generalized tonic-clonic
seizure
Disease
Clinical
Variants
Atonic
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
kids
loss of consciousness,
sudden onset & lasts few
seconds (but very frequent
in number!!)
Complications
a/w developmental
delay
very difficult to treat
(poor prognosis)
conversion
disorders
last up to 45 minutes
(normally seizures last 1-2m
at most)
Stroke
(general)
4th leading
cause of
death
leading
cause of
long-term
disability
blacks are
at higher
mortality
risk than
other
races;
stroke at
earlier age
in blacks
Ischemic
age, M>F,
race (A.A.),
geographic
region
(Stroke belt)
CHF (poor
heart fxn),
cardiomyopathy
(stasis of
blood), HTN,
afib, CAD,
smoking, DM,
EtOH, BMI
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
Stroke
syndromes
Etiologies
aneurysms,
arteriovenous
malformations,
uncont HTN,
tumors,
hemorrhagic
conversion of
infarct, amyloid
angiopathy
Epi
Headache more prominent in bleeding around the brain, into the aneurysms,
5% of
SAH than ischemic
subarachnoid space but not within AVM, idiopathic, strokes
the brain tissue --> raised ICP,
trauma
hydrocephalus, vasospasms
Left MCA
stroke
Right MCA
stroke
Left ACA
stroke
Basilar artery
stroke
(locked in
syndrome) see above for
basilar
pontine
infarction
Treatment
Complications
CT scan -
Vertebral
crossed signs (ipsilateral
artery / PICA face numbness +
stroke
contralateral arm & leg
numbness), vertigo,
dizziness, n/v, Horner's
syndrome (ptosis, misosis,
anhidrosis), ipsilateral ataxia
Quadriplegia or hemiplegia,
nystagmus, crossed signs,
vertigo, diplopia, n/v,
ipsilateral ataxia
Lab/Imaging
10% of
strokes
Subarachnoid
hemorrhage
Right ACA
stroke
Risk factors
Disease
Clinical
Variants
Lacunar
syndromes
Defining Characteristics
Pathogenesis
Etiologies
Epi
long standing
HTN -->
lipohyalinosis -->
ischemia
Risk factors
Lab/Imaging
Tremor
(general)
involuntary rhythmic
oscillating movements
Rigidity
alternating or synchronous
contraction of reciprocally
innervated antagonist muscles
Parkinsons,
Essential
tremor, drugs
(lithium, valproic
acid,
neuroleptics,
stroke), rubral
(stroke, MS)
Parkinsonism
essential
tremor,
physiologic
(caffeine, stress,
meds, drugs)
MS, stroke
Parkinsonism
Parkinsonism
most
common
movement
disorder
check meds!!
Treatment
Complications
Disease
Dystonia
Clinical
Variants
Defining Characteristics
Pathogenesis
involuntary sustained
muscle contractions that
produce twisting/ squeezing
movements & abnl
postures; may be
stereotyped or repetitive;
usually action induced &
worsen w/ stress/ fatigue
Etiologies
excessive, spontaneous
movements that are
irregularly timed, nonrepetitive, & randomly
distributed
involves multiple body parts
Tic
Doparesponsive
dystonia
Huntington's
chorea
tardive
dyskinesia
(iatrogenic Levodopa in PD
pts)
Tourette's
syndrome,
OCD, excessive
blinking
can be suppressed
temporarily by the pt
Myoclonus
rapid, shock-like,
arrhythmic & repetitive
involuntary movements
generalized, focal, multifocal
lasts milliseconds in duration
negative myoclonus
(asterixis) - muscle becomes
silent --> jerky flaps; result of
liver/renal disease, metabolic
d/o, or drugs
kids generalize
dystonias
Epi
Alzheimer's
disease, prion
disease, drugs
Risk factors
Ashkenazi
jews (DYT1)
Lab/Imaging
Treatment
Complications
Disease
Parkinson's
disease
Clinical
Variants
(Parkinsonis
m)
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
bradykinesia + one of
cardinal features (rigidity,
resting tremor, postural
instability)
sporadic
M >= F
(>80%), genetic
(<20%)
5-24/ 10^5
incidence
genetic suscept (inc w/ aging
+ environm
pop)
factors
old age,
MPTP, toxin
exposure
(herbicides,
heavy metals,
wood
preservs),
head trauma
possible
protective
factors?
Caffeine,
smoking, antiinflamm drugs
1. protect neurons
late stage? Orthostatic
(exercise), 2. treat sx (mild - hypotension, aspiration,
amantadine; tremor dementia
anticholinergics; depression anti-depr, anxiety - benzos;
severe sx - dopamine
agonists, LDOPA/carbidopa)
too many side effects or
ineffective? Surgery/ DBS
directed at thalamus,
internal segment of globus
pallidus, or STN
treatment of non-motor sx:
depression, sleep d/o,
orthostatic hypotension, etc.
Disease
Clinical
Variants
Essential tremor
Defining Characteristics
Pathogenesis
Etiologies
Epi
1-6% of
population
(most
common
movement
d/o)
Risk factors
Lab/Imaging
often asymmetric
Complications
FH
bimodal age
of onset
(peaks in
early adult &
later
adulthood)
Treatment
M=F
Progressive
supranuclear
palsy
shock/astonished look on
face, square wave jerks
during fixation & saccadic
intrusions during pursuit,
unable to move eyes
vertically, slow optokinetic
nystagmus (occurs when
following an object w/ eyes),
hyperreflexia, "drunken
stumbling"
Cerebellar
syndromes
Ataxia
Disease
Clinical
Variants
Defining Characteristics
Toxic
syndromes
MachadoJoseph
Disease
(MJD) =
SCA3
Friedreich's
ataxia
(FRDA)
Anti-GAD
ataxia
Pathogenesis
Etiologies
sx onset in late
childhood/
adolescence
Epi
Risk factors
most
Indocommon
European
inherited
races
ataxia (1/3050K)
Lab/Imaging
Treatment
Complications
supportive (balance,
orthotics)
anti-oxidants? HDAC
inhibitors?
MSA
Disease
Huntington's
disease
Clinical
Variants
slowly
progressive,
degenerative
neuropsychiatric
d/o
Defining Characteristics
Juvenile
onset
Multiple
Sclerosis (MS)
Relapsingremitting
(80%),
primary
progressive
(10%),
secondary
progressive,
progressive
relapsing
Pathogenesis
Etiologies
Epi
AD inheritance 5-10/100K
w/ hi penetrance
Risk factors
FH
huntingtin
gene mutation
Lab/Imaging
10% of
Huntington's
is juvenile
onset
gen
predisposition +
abnl immune
system (EBV,
low vitD,
smoker) --> abnl
attack on CNS
Th1 cells
secrete IFN-y &
Th17 cells
secrete IL-17 &
Il-23, recruiting
remission occurs (sx
microglial cells
improvement) when: inc Na+
that display
channels, dec inflamm & NO, &
glial ensheathment; remyelination myelin; B cells
make Abs -(but shorter internodes than nl)
>demyelination
positive sx (tingling, Lhermitte's) - & axonal
transection
hyperexcitable response to
demyelination
leading
cause of
nontraumatic
disability in
young
adults
70%
women,
8500-10K
new cases
per yr
Treatment
Complications
females,
geography
(inc risk if far
from equator),
vitD def,
smoking,
EBV+, FH,
HLA-DRB 1
gene
age of
genetically
onset: 15-50 protected?
Eskimos,
Native
Americans,
Hungarians
Vitamin D supplements
(lowers dz severity),
manage sx
Disease
Dementia
Clinical
Variants
(general)
Defining Characteristics
Pathogenesis
characterized by acquired
memory impairment +
performance impairment in
functional domains (language,
visuospatial skills, identification
skills, executive skills)
Alzheimer's
disease
memory loss
Etiologies
Epi
increased
incidence w/
baby
booming
population
50% of
people >85
have
dementia
dementia + Parkinsonism
(bradykinesia/ rigidity) +
psych sx (hallucinations,
delusions, depression,
anxiety), fluctuating
cognitive state (attention/
arousal), other features (REM
behavior d/o, autonomic
dysfxn, neuroleptic sensitivity,
rapid progression compared
to PD, poorly tolerated
dopaminergics)
distinguished from PD bc
dementia begins at around
same time as dementia sx
Lab/Imaging
Treatment
visuospatial (intersecting
pentagons)
most
common
type of
dementia
F>M
thought to be an intermediate
syndrome between AD & PD
decreased cortical ACh &
striatal dopamine
formation of amyloid plaques,
neurofibrillay tangles, & Lewy
bodies
cortical Lewy bodies & Lewy
neurites widespread in DLB
(correlate w/ dementia severity); asynuclein = major component of
Lewy bodies
at risk genes?
APOE4,
mutation in
alphasynuclein
age, Down
syndrome,
head trauma,
depression,
HTN, hypercholesteremia
, hi
homocysteine
, low B12/
folate
symptomatic? AChE
inhibitors (donepezil,
galanthamine, rivastigmine),
memantine
Neuroprotective? VitE
protective?
Education,
exercise, Med
diet, NSAIDs,
statins, red
wine
10-20% of
dementia
M>F
age of
onset? 5080
FH
cannot be distinguished
neuropathologically from
Parkinson's dementia
Complications
very vulnerable to
delirium
Risk factors
Disease
Clinical
Variants
Frontotemporal
dementia
Defining Characteristics
Consciousness
Etiologies
Epi
Risk factors
syndromic dx
Delirium
Pathogenesis
histology: Frontotemporal
lobar degeneration w/ lesions
displaying Pick bodies
(intracellular, aggregated tau
protein), immunoreactivity to
TDP-43 or FUS
MRI: frontotemporal atrophy
(bvFTD), subtle left atrophy
(PPA)
Lab/Imaging
I WATCH
DEATH
(infection,
withdrawal,
trauma, CNS
path, hypoxia,
deficiency of
vitamins,
endocrinopathy,
acute vascul
insult, toxins,
heavy metals)
brain mets
(melanoma,
colon, breast,
prostate, renal
transitional cell)
strongly
associated
with
morbidity &
mortality
dementia
patients
Treatment
Complications
Disease
Clinical
Variants
Comatose
Defining Characteristics
cannot be aroused to
consciousness despite
stimuli used
decorticate posturing
(flexor)- damage to upper
midbrain
decerebrate posturing
(extensor) - damange to lower
midbrain/ upper pons
Cheynes- Stokes resp - liver
failure or toxic insult to brain
Central neurogenic
hyperventilation - midbrain
lesion
apneusis - ischemic stroke to
pons
cluster breathing - lower
pons lesion
ataxic breathing - medulla
lesion
Persistent
vegetative state
(PVS)
Pathogenesis
wakefulness without
awareness
Etiologies
Epi
Risk factors
Lab/Imaging
BS: trauma,
brainstem
stroke/ hemorr
Both
hemispheres:
bilateral
subdural
hematomas,
large/ lots brain
tumors, inc ICP,
degen dz
metab/toxic:
hypoxia,
ischemia, hi/low
gluc, hi/low Na+,
hypo-thyroidism,
drugs, liver
failure,
hypercarbia,
sepsis,
meningitis
hypoxic
ischemic
encephalopathy
(most common
cause of PVS)
Treatment
Complications
severely altered
consciousness w/ minimal
but definite behavioral
evidence of self or
environment
reproducible evidence of
awareness (speech,yes/no
responses, purposeful
behaviors like following
commands)
emergence: functional
interactive communication
and/or functional use of
two different objects
hypoxic
ischemic
encephalopathy,
TBI, stroke,
neurodegen dz,
metabolic d/o,
tumors,
congenital or
developmental
d/o
can be permanent or
transitional state
Disease
Clinical
Variants
Brain death
Defining Characteristics
Pathogenesis
Etiologies
Epi
documented loss of
irreversible loss of all brain &
consciousness (coma) + no brain stem function
brain stem reflexes + apnea
Risk factors
Lab/Imaging
Treatment
medical record
documentation: etiology &
irreversibility of condition,
absent brainstem reflexes,
absent motor response to
apnea test (no respirations at pain, rpt neuro exam,
absence of respiration w/ hi
CO2>60 mmHg)
pCO2, justification & results
of confirmatory tests, time
confirmatory tests (cerebral
angiography, EEG, transcranial of death (time last test is
completed)
doppler u/s, isotope
angiography) if pt cannot reliably
undergo clinical testing
components
NO motor/facial responses
to pain (nail bed pressure,
sternal rub, nasal tickle),
absent pupillary response,
round/ oval pupils, no doll's
eye or caloric testing
movements (eyes stay fixed
in skull), absent corneal
reflex, absent cough
response to bronchial
suctioning
Complications
Axonal
polyneuropathy
(general)
Metabolic,
majority of
endocrine (DM), polymeds/ toxins,
neuropathy
nutritional (B12
def), connective
tissue (SLE,
Sjogren's)
Diabetic
peripheral
neuropathy
Myelinopathy
(general)
30%
prevalence
among
diabetics
Disease
Clinical
Variants
GuillainBarre
Syndrome
(GBS)
Defining Characteristics
Pathogenesis
ACUTE ascending
weakness, absent reflexes,
can involve CN7 (facial
paralysis) & autonomic
dysfxn (cardiac irregularities,
HTN, hypotension)
Etiologies
Epi
most
common
cause of
acute
generalized
paralysis
0.61.9/100K
Risk factors
Lab/Imaging
all age
groups
Treatment
Complications
majority of pts
recover; 15% have NO
residual deficits, 50-65%
are restored 2/3 normal
fxn, 10% have
persistent severe
weakness
mechanical ventilation
a/w 15-30% mortality
Myasthenia
gravis (MG)
fluctuating weakness of
VOLUNTARY muscles -->
diplopia, ptosis, difficulty
swallowing/ breathing
weakness may fluctuate in
intensity throughout the day
nl pupillary responses
insidious onset,
exacerbated by menstrual
period/ pregnancy
blocks of neuromuscular
transmission due to
AUTOANTIBODIES binding to
AChR on postsynaptic
membrane --> 1) decrease in
number of available receptors, 2)
less surface area due to
architectural change of
postsynaptic membrane --> less
ability to depolarize the
membrane --> chronic muscle
weakness
Anti-cholinesterase drugs
can be a/w thymic
provide symptomatic benefit tumor, thyrotoxicosis,
RA, SLE
steroids if poor response to
AChE inhibitors
aspiration pneumonia,
myasthenic crisis -->
thymectomy (symptomatic respiratory weakness
benefit or remission) considered in all pts <60
cramps, fasciculations
NO sensory loss, NO ptosis
or eye movement probs
progressive course!
Disease
Clinical
Variants
Poliomyelitis
Defining Characteristics
Pathogenesis
neurotropic enterovirus w/
predisposition for ventral horn
in spinal cord & motor cranial
nerve nuclei --> LMN
destruction
Etiologies
Epi
new cases
eradicated
in U.S. but
cases of
post-polio
syndrome
Kennedy's
disease
X-linked bulbospinal
muscular atrophy
Lab/Imaging
4-10/100K
SMA1 =
most
common
motor
neuron dz
mostly
males
median age
44
Treatment
Spinal
Muscular
Atrophy
(SMA)
Risk factors
Complications
Disease
Clinical
Variants
Amyotrophic
Lateral
Sclerosis
(ALS)
Defining Characteristics
Pathogenesis
Etiologies
90-95%
sporadic;
5-10% AD
Epi
Risk factors
1/100K
Lab/Imaging
avg age =
mid 50s
cause unknown?
Treatment
Riluzole - prolongs
survival (2-3m); must
monitor LFTs during tx
Nuedexta helps bulbar sx
M:F 3:2
Thought to be a continuum that
eventually converge to have ALS
(i.e. progressive muscular atrophy
is LMN and primary lateral
sclerosis is UMN; ALS is in the
middle of these two)
U.S. prev =
30K
10%
prevalence
by age 3540
AGE, obesity
no cure - progressive
& fatal
variable dz course - if
initial rapid
presentation then
rapid progression
50% die w/I 3-4y
20% live 5+y
10% live 10+y
PT/OT/Speech therapy
bipap for breathing
nutrition
FTD in 5-20%
C-PAP
Cardiovascular
disease (HTN) and
stroke risk!!
Sleep apnea
Complications
lifestyle modifications
MOST COMMON
CAUSE OF DEATH?
Respiratory dysfxn
(restrictive pattern; sx?
Inability to lay flat,
frequent nighttime
arousal, EDS, exertional
dyspnea)
Increased rates of
mortality
Insomnia
Narcolepsy
(general)
most
prevalent
sleep sx
F>M
molecular
mimicry &
certain
infections?
1/2000
people
Polysomnogram: short
nocturnal REM latency, signs
of disruptive nocturnal sleep,
periodic leg movements
Behavioral strategies:
short/scheduled naps,
consistent sleep/wake
schedule, exercise, good
sleep hygiene, avoid
alcohol/ caffeine/ nicotine
Multiple Sleep Latency Test
(MSLT) measures the amount before bed
of time it takes to fall asleep;
EDS treatment: Modafenil
latency period < 8 minutes
suggests narcolepsy
cataplexy tx: Sodium
oxybate(date rape drug),
CSF sample lacking
SSRIs, TCAs, SNRIs
hypocretin
HLA testing: HLA DQB 10602
obesity (hypocretin
system also related to
leptin, ghrelin, insulin, &
thyroid hormone)
Disease
Clinical
Variants
Restless leg
syndrome (RLS)
Defining Characteristics
Pathogenesis
Etiologies
most often
familial (AD)
pregnancy,
iron & B12
deficiencies,
anemia
Epi
Rapid Eye
(general)
Movement Sleep
Behavior
Disorder (RBD)
Risk factors
mostly men
> 50y.o.
(unless antidep
related)
Lab/Imaging
Treatment
Dopaminergics
Complications
Physical measures to
ensure safety: remove
dangerous nearby objects,
bedrails, soothing alarm
RBD is dangerous!!!
Change anti-depressants
to wellbutrin
Pharm tx: Clonazepam,
Melatonin
Acute onset
Iatrogenic (anti-depressants)
Withdrawal - Alcohol (chronic
EtOH --> downregulation of GABA -> delirium tremors that look like
RBD); Barbituates/
benzodiazepines
structural lesions - Pontine
lesions (ischemia, hemorrhage,
tumor, demyelination,
inflammation); limbic cortex
(limbic encephalitis)
Disease
Non-REM
arousal
disorders
Clinical
Variants
Defining Characteristics
Confusional
arousals
overlapping spectrum
(confusional arousals most
basic, sleep walking adds
Sleep terrors motor activity, & sleep
terrors add fear &
Somnautonomic activation w/o
ambulism
memory of event)
(sleep
walking)
Occurs during 1st half of
Pathogenesis
Etiologies
(general)
Risk factors
Lab/Imaging
disorders
of
childhood
28 million
Americans
18%
women, 6%
men
peak age:
25-55 y
<10% able
to fxn during
HA
Common
migraine
Hemiplegic
migraine
Basilar
migraine
Cyclical
vomiting
migraine
common migraine +
"AURA" - visual, dysphasia,
hemisensory deficits
(neurological deficits
reversible >5m but <60m)
Prophylaxis based on
comorbidities w/
headaches: AED
(Topamax, Gabapentin,
valproic acid), Anti-HTN
(propanolol, CCB), Antidepressants (TCAs,
SSRIs, SNRIs)
IV DHE if continuous
headache (need EKG
before using - inc stroke/ MI
risk)
Treatment
safe environment
if occur in
adulthood,
consider
occult cause
of arousal
(OSA)
Migraine
Epi
FH
Complications
Disease
Clinical
Variants
Defining Characteristics
Benign
Paroxysmal
Vertigo of
Childhood
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Complications
Sinus headache
headache attributed to
rhinosinusitis
90% of sinus
headache patients
have MIGRAINE!!
also called
rebound or
drug-induced
headache
Tension
headache
Trigeminal
Autonomic
Cephalgias
Cluster
headache
severe unilateral
orbital/supraorbital/
temporal pain lasting 15m180m (EXTREME
INTENSITY EXCRUCIATING
UNILAT HA)
associated with one of the
following signs on the painful
side: conjunctival injection,
lacrimation, nasal congestion,
rhinorrhea, forehead/facial
sweating, miosis, ptosis,
eyelid edema
freq attacks: 1 every other
day to 8x/d
Chronic
Paroxysmal
hemicrania
Ibuprofen,
Goody's
powder, tylenol
non-pharm prophylaxis:
spinal manipulation, neck
exercises, therapeutic
touch/ self massage/
stretching
regular lifestyle/ sleep,
exercise, stress mgmt
Sumatriptan injection or
nasal spray (>90%
effective), indomethacin,
consider prednisone
Oxygen therapy
DHE - IM, subq, IV
Prophylaxis: Verapamil,
Topiramate, Melatonin,
Lithium carbonate
Surgery: central
parasympathetic
interruption, sensory
trigeminal interruption,
radiofrequency
thermocoagulation
Disease
Clinical
Variants
Hemicrania
continua
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
Indomethacin
non-remitting, remitting
pain 24/7 w/ +/- autonomic
sx, exacerbations w/
coexisting migraines or
cluster HA, "foreign body"
sensation in eye, ice pick
HA
Conjunctivitis
(general)
Bacterial
microbes,
viruses, toxins,
allergens, tear
deficiency
S. aureus, Strep
pneumo, H.flu,
Pseudomonas,
N. gonorrhea
hyperpurulent?? N.
gonorrhea
Viral
pre-auricular
lymphadenopathy - pink
eye
Allergic
HSV keratitis
Herpes Zoster
Ophthalmicus
Blepharitis
If N. gonorrhea as
causative agent REQUIRES systemic
antibiotics & lavage
ADENOVIRUS:
Eye exam: conjunctival
follicles (lymphoid aggregates)- Cool compresses, topical
decongestants or artificial
adenovirus
tears; refer if severe pain or
decreased vision
Acyclovir, steroids
Acyclovir
Complications
Disease
Stye
Chalazion
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
S.aureus
usually self-limiting
Dacrycystitis
Dacryoadenitis
Orbital cellulitis
previous facial
trauma
obstructing the
nasolacrimal
passage
infxn, inflamm,
granulomatous
hospitalization
Subconjunctival
hemorrhage
Scleritis
Hyphema
SELF-LIMITING
Hypopyon
Corneal abrasion
Orbital fracture
trauma, blood
thinners
tear of iris or
sphincter
muscle
corneal
abrasions
(contact lenses),
previous
surgeries, septic
emboli
denuded epithelium from abrasion -> irregular fibers/ scarring in
stroma --> vision loss
topical antibiotic
Complications
Disease
Optic neuritis
Clinical
Variants
Defining Characteristics
Pathogenesis
Etiologies
MS
Epi
Risk factors
F>M
Lab/Imaging
ages 15-45
(younger
population)
PAINLESS, permanent
visual loss
Papilledema
painless, BILATERAL
intracranial
ANY age
mass lesions,
hydrocephalus,
meningeal
processes,
idiopathic,
venous
thrombosis
Central retinal
artery occlusion
Glaucoma
hypercoagulable
state
Complications
Anterior
Ischemic Optic
Neuropathy
Treatment
DM & Chronic
HTN
FH (6x risk)
A.A.,
Hispanics,
elderly
Pilocarpine
systemic carbonic
anhydrase inhibitor to lower
pressure enough for surgery
iridotomy or ididectomy
blindness!!!!!
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
Uveitis
Macular
degeneration
congenital
(rubella)
adult (agerelated)
Epi
Risk factors
Lab/Imaging
FH,
Caucasians,
females, light
eyes,
smoking,
heart dz,
HTN, UV light
exposure,
poor nutrition,
AGE
advanced age,
DM, infection,
corticosteroid
use
Treatment
sarcoidosis,
ulcerative colitis,
ankylosing
spondylitis
CMV retinitis
Cataracts
Etiologies
cataract extraction
procedures (most common
smudges on retroillumination - surgery in U.S.)
subcapsular
white cortical cataracts - DM
Myopia
Enucleation
Retinoblastoma - kids,
white eye reflex
malignant melanoma adults
"near sightedness" =
unable to see far
Hyperopia
Astigmatism
Complications
Disease
Clinical
Variants
Presbyopia
Defining Characteristics
Pathogenesis
Etiologies
Epi
Risk factors
Lab/Imaging
Treatment
ages 40-50
reading glasses
Complications
Rubiosis iridis
Ectropion
Extropion
Diabetic
retinopathy
(general)
Nonproliferative
lipid exudates +
microaneurysms
longer
duration of
DM
lack of retinal capillary endothelial
integrity --> microaneurysms +
fluid/ protein/ lipid exudates
increased microthrombus
formation --> retinal ischemia -->
neovascularization of iris & release of VEGF-->
neovascularization into vitreous
retina
cavity --> hemorrhage of these
weak vessels --> retinal
pre-retinal or vitreous
detachment
hemorrhage
profound vision loss
neovascular
glaucoma, DM
(proliferative
diabetic
retinopathy),
central retinal
vein occlusion
Disease
Clinical
Variants
Defining Characteristics
Pathogenesis
HTN retinopathy
Retinal
detachment
Temporal (giant
cell) arteritis
Etiologies
Epi
age >50
(usually
70s,80s)
Risk factors
Lab/Imaging
Treatment
Complications
follow pt for
corticosteroid side
effects (BMD, etc)
Screening /
Education
Screening /
Education
Screening /
Education
any diagnosed
seizure? No
driving or
operating heavy
machinery,
swimming,
bathing in tubs,
ladders until
seizure free
avoid alcohol,
sleep deprivation
urge AED
compliance
f/u MRI
Screening /
Education
Screening /
Education
Screening /
Education
Framingham
stroke risk score
(age, untx SBP or
tx SBP, DM,
smoking, CVD,
Afib, LVH)
2ndary
prevention?
Antiplatelet tx
(aspirin if
atheroscl, small
vessel dz),
anticoag tx
(coumadin if
cardioemb,
hypercoag),
carotid
endaterectomy if
stenosis
lifestyle mods >>
meds
Screening /
Education
Screening /
Education
Screening /
Education
Screening /
Education
PD progresses
within 15-20y
timeframe
Screening /
Education
Screening /
Education
Screening /
Education
genetic testing
not done in
unaffected
children at risk!
Screening /
Education
Screening /
Education
Screening /
Education
patient
autonomy
Screening /
Education
must talk to
family members
about what to
expect as brain
dead testing is
done
(spontaneous
movements
after brain
death)
give family the
option to
withdraw care!
Organ donation
Screening /
Education
Screening /
Education
inactivated polio
vaccine!
Screening /
Education
nutritional &
caregiver
education
end of life
decisions
hospice
Screening /
Education
Screening /
Education
Concerned about
use of OCP,
stroke/ HTN/
OSA risk in
migraine
patients
Screening /
Education
Screening /
Education
VERY
CONTAGIOUS!!!
Avoid social
contacts!
Screening /
Education
Screening /
Education
comprehensive
eye exam for
everyone after
age 40
early eye exams
if FH
Screening /
Education
smoking
cessation
wear sunglasses,
get eye exams,
eat healthy,
control vascular
dz
prevention
involves
controlling
comorbidities
Screening /
Education
T1DM: dilated
eye exam q 3-5y
within dx & yearly
afterwards
T2DM: dilated
eye exam @ time
of dx, yearly
afterwards
Screening /
Education
Bacteria
Streptococcus
pyogenes
Staphylococcus aureus
N. gonorrhea
Classification
GAS
Gram +/-
Morphology
Characteristics
Catalase neg
Facultative anaerobe
hyaluronic capsule
Cocci in pair/chains
(mucoid appearance)
strongly B-hemolytic
Bacitracin susceptible
Cocci in grape-like
clusters
Catalase +
Coagulase + (good test
to distinguish S. aureus
from other Staph)
Facultative anaerobe
Beta-hemolytic
Mannitol +
Yellow colonies
(CoPS)
Intracellular
diplococci
associated with
neutrophils
Oxidase+
grows w/ CO2
Virulence factors
Diseases
Strep throat
M surface protein (anti(pharyngitis)
phagocytic;
Rheumatic fever
superantigen; >90
Impetigo
types)
Strep TSS
Glomerulonephritis
SPEs (superantigens
SSTIs
that superstimulate T
Cellulitis
cells --> inflam
Erysipelas
cytokines)
NF
CA-MRSA: SCCmec
type IV cassette w/
methicillin resistance;
PVL (toxin that kills
leukocytes by forming
SSTIs
pores in their
Cellulitis
membranes); PFGE
NF
type USA 300
SSI
Endocarditis
General: Catalase +
Pericarditis
(anti-phagocytic),
Pyomyositis
clumping
Meningitis
factor/techoic acid/
Food poisoning
proteins A&B
TSS
(adherence), lipases
(abscess formation),
leukocidin (lysis of
phagocytes), MANY
toxins!
Resistant to human
serum - Por1A
Population
Transplant patients
Skin break
Disease
Risk factors
Age
UV exposure
Type 1- 3 skin
Duration of immunosuppressants
Skin cancers
Intensity of immunosuppressants
HPV
Hx of skin cancer
CD4 lymphopenia
Pathogen
Human bite
(mouth pathogens)
Eikenella corrodens
Cat bite/puncture
Pasteruela multocida
Dog bite/puncture
C. canimorsus
Fresh water
Salt water/fish
Aeromonas hydrophilia
Erysipelothrix rhusiopathiae
Mycobacterium marinum
Aquarium
Spa/ hot tub
Psuedomonas aeruginosa
Gas gangrene
Trauma
Cirrhosis & salt water
Vibrio vulnificus
Streptococci
Edema
S
P
A
C
E
K
Nosocomial Infections
Serratia
Pseudomonas
Acinetobacter
Citrobacter
Enterobacter
Klebsiella