Diseases

Front 1

Hereditary Spherocytosis

Back 1

--Autosomal dominant
--Defect in ankyrin, band 4.1, or spectrin (Proteins interacting with RBC membrane skeleton and plasma membrane--fuzzy coat).
--Less membrane --> small and round RBCs with no central pallor
--Increased MHCH, Increased RDW

--Findings: Splenomegaly, aplastic crisis (B19 infection), Howell-Jolly bodies present after splenectomy.

Labs: Positive osmotic fragility test.

Treatment: Splenectomy

Front 2

Myasthenia Gravis

Back 2

Most common Neuro-muscular Junction disorder.
--Autoantibodies to postsynaptic Nicotinic AChR
--Associated with thymoma.


Sx: ptosis, diplopia, and general weakness. muscle weakness worsens with muscle use

Dx: Nerve stimulation/compound muscle AP test.

Tx: Reversal of sx occurs with AChE inhibitors (edrophonium test distinguishes under-and overdosing).

Front 3

Cystic Fibrosis

Back 3

--Autosomal Recessive--most common lethal genetic disease of caucasians-- defect in CFTR gene on chrom. 7, common deleteion of Phe 508.
---Mutation causes abnormal protein folding, resulting in degradation of channel before reaching cell surface.
--CFTR channel actively secretes Cl- in lungs and GI tract and actively reabsorbs Cl- from sweat.
--Defective Cl- channel --> Secretion of abnormally thick mucus that plugs lungs, Pancreas, and liver-->

Sx: recurrent pulmonary infections (Pseudomonas species and S. aureus), Chronic bronchitis, bronchiectasis, pancreatic insufficiency (malabsorption and steatorrhea), meconium ileus in newborns.

--Infertility in males due to bilateral absence of vas deferens.
-Fat soluble vitamin deficiencies (A, D, E, K). Can present as failure to thrive in infancy.

DX: Increased concentration of Cl- ions in sweat is diagnostic

Tx: N-acetylcysteine to loosen mucous plugs (cleaves disulfide bonds w/in mucous glycoproteins).

Front 4

Kartagener's Syndrome ; also called primary ciliary dyskinesia/immotile cilia syndrome.

Back 4

--Dynein arm defect in axoneme structure of cilia.
--Dynein-ATPase that links peripheral doublets and causes bending of cilum by differential sliding of doublets.

SX: Male and female infertility (sperm immotile)
-bronchiectasis,
-recurrent sinusitis (bacteria and particles not pushed out); associated with situs inversus.

Front 5

Phemphigus Vulgaris

Back 5

-Fatal autoimmune skin disorder (Type II hypersensitivity)
--IgG antibodies attack desmosomes.
--Immunofluorescence reveals antibodies around cells of epidermis in a reticular or netlike pattern.

Sx: Acantholysis--Intraepidermal bullae involving the skin and oral mucosa
-causes severe blistering due to water loss

Dx: Positive Nikolsky's sign (separation of epidermis upon manual stroking of skin).

Front 6

Prions

Back 6

--Disease caused by conversion of a normal cellular protein termed prion protein (PrPc) to a beta-pleated form (PrPsc), which is transmissible.
--PrPsc resists degradation and facilitates conversion of still more PrPc to PrPsc.

Disease: Accumulation of PrPsc results in spongiform encephalopathy
--dementia
--ataxia
--Death

Note: It can be sporadic (Creutzfeldt-jakob diseases--rapidly progressive dementia), inherited (Gerst-mann-straussler-Scheinker syndrome), or acquired (Kuru).

Front 7

Scurvy

Back 7

--Caused by lack of Vitamin C
--Vitamin C is co-factor required for hydroxylation of proline and lysine in synthesis (takes place in rER).

Sx: Swollen gums
--bruising
--hemarthrosis
--anemia
--poor wound healing
--Weakend immune response (WHY?)

Aside: British sailors carried limes to prevent scurvy (origin of the word limey).

Front 8

Ehlers-Danlos Type VII

Back 8

--Lack of Procollagen peptidase (enzyme that breaks down procollagen to tropocollagen outside the cell membrane).
--Results in hyperflexible joints, dislocations, and soft skin.

Front 9

Ehlers-Danlos Type IV

Back 9

---Due to deficiency in type III collagen
---Aneurysms and intestinal rupture common.

Front 10

Emphysema

Back 10

--Due to deficiency in alpha1-antitrypsin.
--Results in excess elastase activity.

-Since can't let air out (ie recoil) develop barreled chest.

Front 11

Marfan's Syndrome

Back 11

--Connective tissue disorder affecting skeleton, heart, and eyes.

Defect:
(1) Defect in fibrillin gene

Symptoms
--Tall with long extremities
--Pectus Excavatum (chest caved in appearance)
--hyperflexible joints
--long, tapering fingers and toes (arachnodactyly)
--subluxation of lens
--cystic medial necrosis of aorta--> aortic incompetence and dissecting aortic aneurysms; floppy mitral valve.


Notes:

Front 12

Pitting Edema

Back 12

-Characterized by abnormal build up of interstitial fluid in ECM.

Causes:
1) Blocked lymphatics--surgery, elephantiasis.
2) Blocked Venous return--compromised veins
3) Liver Disease--Insufficient albumin to pull H20 back in vessel
4) Increased vascular permeability (histamine from mast cells)
5) Hypertension (due to increased hydrostatic pressure at arterial end of capillary bed.
6) Starvation -- causes lack of plasma proteins that results in H20 remaining in ECM

Front 13

Myxedema

Back 13

Due to over production of GAG's during hypothyroidism

--If you push on it, will not push out.

Front 14

Sickle Cell Anemia

Back 14

--8% of blacks carry the HbS trait; 0.2% have the disease.
--Sickeled cells = crescent shaped RBCs.
--"Crew cut" on skull x-ray due to marrow expansion from increased erythropoiesis (also in thalassemias)
--Newborns are asymptomatic owing to increase HbF and decreased HbS.

Mutation: HbS mutation is a single amino acid replacement in beta chain (substitution of normal glutamic acid with valine) at position 6. Point mutation.

Pathogenesis: Deoxygenated HbS polymerizes. Low O2 or dehydration precipitates sickling. Results in anemia and veno-occlusive disease.

--Heterozygotes (sickle cell trait) have resistance to malaria.

Complications in homozygotes (sickle cell disease)
1) Aplastic crisis (due to Parvovirus B19 infection).
2) Autosplenectomy --> Increased risk of infection with encapsulated organisms (Howell-Jolly bodies); functional splenic dysfunction occurs in early childhood.
3) Salmonella osteomyelitis
4) Painful crisis (vaso-occlusive)
5) Renal papillary necrosis (due to low O2 in papilla) and microhematuria (medullary infarcts)
6) Splenic sequestration crisis

Tx: Hydroxyurea (Increase HbF) and bone marrow transplantation.

Front 15

Hemoglobin C Defect

Back 15

--Glutamic acid to lysine mutation at position 6 in chain mutation; patients with HbSC (1 of each mutant gene) have milder disease than do HbSS patients.

Front 16

Alpha-thalassemias

Back 16

Prevalent in Asian and African populations
Defect: alpha globin gene mutations --> Decreased alpha globin synthesis.

--Deletion of four genes is incompatible with life--> formation of Hb Barts (gamma 4) which causes hydrops fetalis.

--Deletion of 3 genes --> HbH disease (Beta 4).

--Deletion of 1-2 genes is not associated with significant anemia.

Front 17

Beta-thalassemia

Back 17

--Prevalent in Mediterranean Populations
DEFECT: point mutations in splicing sites and promoter sequences.

Beta-thalassemia minor (heterozygote):
1) Beta chain is underproduced
2) Usually asymptomatic
3) Diagnosis confirmed by increased HbA2 (> 3.5%) on electrophoresis

Beta-thalassemia major (homozygote).
1) Beta chain is absent --> Severe anemia requiring blood transfuction (secondary hemochromatosis).
2) Marrow expansion ("crew cut" on skull x-ray)--> skeletal deformities. Chipmunk facies.

Both major and minor --> Increase HbF (alpha2gamma2).

HbS/Beta-thalassemia heterozygote: Mild to moderate sickle cell disease depending on amount of beta-globin production.

Front 18

Inclusion Cell Disease

Back 18

--Rare inherited condition
--Defect: Failure of golgi to add mannose-6-phospate to lysosomal proteins thus, enzymes are secreted outside the cell instead of being targeted to the lysosome.

Pathology: Primary lysosomes do NOT have hydrolytic enzymes to degrade complex substrates. Thus, undigested substrates accumulate as large inclusions in cytosol.

Symptoms:
--Psychomotor retardation and early death.
--coarse facial features
--Clouded corneas,
--High plasma levels of lysosomal enzymes.

Front 19

Chediak-Higashi syndrome

Back 19

--Autosomal recessive disease

Defect: Microtubule polymerization defect

Symptoms:
--Recurrent pyogenic infections (especially staph aureus) due to defects in chemotaxis, degranulation, and bactericideal activity.
--Decreased phagocytosis.
--Partial albinism (vesicles of melanin can't be transported out)
--Peripheral neuropathy

Symptoms:
--Silvery hair

Front 20

Normal Collagen Synthesis

Back 20

Collagen Synthesis --Transcription in nucleus
--Translation with in rER
--In rER, get hydroxylation of proline and lysine (formation of Pro-collagen in rER).
--Secretion via Golgi apparatus
--Procollagen Peptidase cleaves procollagen to form tropocollagen molecules outside cell membrane.
--Tropocollagen molecules form collagen fibril in extracellular matrix.
--Lysyl oxidase covalently links hydroxylysine molecules of adjacent tropocollagen molecules to form insoluble fibrils.

NOTE: Hydrogen bonding between hydroxyproline molecules of adjacent polypeptide chains holds the chain together too (on top of covalent bonds).

Front 21

Osteogenesis imperfecta

Back 21

--Autosomal dominant genetic bone disorder (brittle bone disease).

Defect: Variety of gene defects. Most common is abnormal type I collagen

Symptoms:
(1) MULTIPLE fractures w/ MINIMAL trauma; may occur during birty process.
(2) BLUE SCLERAE due to translucency of connective tissue over the choroid
(3) Hearing loss (abnormal middle ear bones).
(4) Dental imperfections due to lack of dentin.

NOTES:
(1) May be confused with child abuse.
(2) Type II is fatal in utero.

Front 22

Alport's Syndrome

Back 22

--Abnormal type IV collagen

Defect: Variety of gene defects. Most common is X-linked recessive.

Symptoms:
(1) Progressive hereditary nephritis and deafness.
(2) May be associated with ocular disturbances.

Notes: Type IV collagen is important component of basement membrane of kidney, ears, and eyes.

Front 23

Prader-Willi syndrome

Back 23

--One of the two genomic imprinting diseases.

Defect: During normal gametogenesis, Prader-willi gene of maternal chromosome 15 is methylated (imprinted)--inactivated and is demethylated of paternal chromosome 15--activated.
--Microdeletion of entire gene site on PATERNAL chromosome 15 --> Prader-Willi syndrome.

Symptoms:
(1) Mental retardation, short stature, hypotonia at birth

(2) Obesity (OVEREATING),
(3) hypogonadism

NOTES:

Front 24

Angelman Syndrome

Back 24

--One of two genomic imprinting disease.

Defect:
--Normal Angelman gene of materal chromosome 15 during gametogenesis is demethylated (activated) and paternal chromosome 15 angelman gene imprinted (inactivated).
--Microdeletion of entire gene site on maternal chromosome 15--> angelman syndrome.

Symptoms:
(1) Mental retardation
(2) Wide-based gait (resembles a marionette)
(3) Inappropriate laughter ("happy puppet" syndrome).

Notes:

Front 25

Neurofibromatosis type 1 (von Recklinghausen's disease)

Back 25

Defect: Mutation of gene coding for neurofibromin on long arm of chromosome 17.


Symptoms:
(1) Cafe-au-lait spots
(2) Neural tumors
(3) Lisch nodules (pigmented iris hemartomas)
(4) Skeletal disorders (scoliosis) and optic pathway gliomas

NOTES:

Front 26

Neurofibromatosis type 2

Back 26

Defect: Defect of NF2 gene on chromosome 22

Symptoms:
(1) Bilateral acoustic schwannomas (tumor of myelin forming cells around the 8th cranial nerve).

Front 27

Familial Hypercholesterolemia (hyperlipidemia type IIA)

Back 27

Defect:
--Defective or absent LDL receptor

Symptoms:
(1) Elevated LDL.
(2) Heterozygotes (1:500) cholesterol = 300 mg/dL
(3) Homozygotes (rare) cholesterol = 700 + mg/dL
(4) Severe atherosclerotic disease early in life
(5) Tendon xanthomas (especially in achilles tendon).

Front 28

Tuberous Sclerosis

Back 28

Defect:

Symptoms:
(1) Facial lesions (adenoma sebaceum)
(2) hypopigmented "ash leaf spots" on skin
(3) Cortical and retinal hamartomas
(4) Seizures
(5) Mental retardation
(6) Renal cysts and renal angiomyolipomas
(7) Cardiac rhabdomyomas
(8) Increased incidence of astrocytomas.

Notes: Incomplete penetrance, Variable presentation.

Front 29

Autosomal-dominant polycystic kidney disease (ADPKD)

Back 29

Defect:
-Mutation of APKD1 of chromosome 16.


Symptoms:
(1) ALWAYS BILATERAL, massive enlargement of kidneys due to multiple large cysts.
(3) Flank pain, hematuria, hypertension, and progressive renal failure.
(4) Associated with polycystic liver disease
(5) BERRY ANEURYSM
(6) Mitral valve prolapse.

NOTES:

Front 30

Huntington's Disease

Back 30

Defect:
--Gene located on chromosome 4; Trinucleotide repeat disorder: (CAG)n. HINT: "Hunting 4 food."

Symptoms:
(1) Depression
(2) Progressive dementia
(3) Choreiform movements
(4) caudate atrophy
(5) Decreased levels of GABA and Ach in brain.

NOTES: Symptoms manifest in people between 20 and 50.

Front 31

Von Hippel- Lindau Disease

Back 31

Defect:
--Associated with deletion of VHL gene (tumor suppressor) on chromosome 3 (3p) --> constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors.

NOTES:
HIF= Hypoxia Inducible factor
Von Hippel-Lindau= 3 words for chromosome 3.


Symptoms:
(1) hemangioblastomas of retina/cerebellum/medulla (about half of affected individuals develop multiple bilateral renal cell carcinomas and other tumors.

Front 32

Duchenne's Muscular dystrophies

Back 32

--One of two muscular dystrophies

Defect: X-linked frame-shift mutation--> DELETION of dystrophin gene--> accelerated muscle breakdown.

Symptoms:
(1) Weakness begins in pelvic girdle muscle and progresses superiorly.
(2) Pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle; cardiac myopathy.
(3) Use of Gower's maneuver, need upper extremities to stand up.

Dx:
(1) Look for Increased CPK
(2) Muscle biopsy



Notes:
--Onset BEFORE 5 years of age.
--Dystrophin gene (DMD)--> longest gene in humans.
--Dystrophin anchors muscle fibers (mostly in skeletal and cardiac).

Front 33

Becker's muscular dystrophies

Back 33

Defect:
--X-linked MUTATED dystrophin gene.
--Less severe than duchenne's (deletion)

Symptoms:
(1) Weakness begins in pelvic girdle muscle and progresses superiorly.
(2) Pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle; cardiac myopathy.
(3) Use of Gower's maneuver, need upper extremities to stand up.


Dx:
(1) Look for Increased CPK
(2) Muscle biopsy

NOTES:
--Symptoms same as Duchenne's, but less severe.
--STARTS in adolescence or early adulthood.

Front 34

Fragile X syndrome

Back 34

--One of the Trinucleotide repeat disorders (CGG)n

Defect:
--X-linked defect affecting methylation and expression of FMR1 gene.
--Associated with chromosomal breakage.


Symptoms:
(1) 2nd most common cause of genetic mental retardation (#1 = down syndrome).
(2) Macro-orchidism (enlarged testes)
(3) long face with a large jaw
(4) Large everted ears
(5) autism
(6) Mitral valve prolapse


NOTES

Front 35

Trinucleotide repeat expansion Diseases (Simple list)

Back 35

(1) Huntington's disease (CAG)
(2) Myotonic dystrophy (CTG)
(3) Fragile X syndrome (CGG)
(4) Friedreich's ataxia (GAA)

Front 36

Down Syndrome

Back 36

Defect:
--Trisomy 21 (mechanism?)


Symptoms:
(1) Mental retardation (#1 cause)
(2) FLAT FACIES
(3) prominent EPICANTHAL FOLDS
(4) SIMIAN CREASE
(5) Gap between 1st two toes, duodenal atresia
(6) Congenital Heart Disease (most commonly septum primum-type ASD).
(7) Associated with Increased risk of ALL and Alzheimer's disease (>35 years of age).

NOTES
(1) 95% due to meiotic non-disjunction of homologous chromosomes (ass. w/ advanced maternal age).
(2) 4% due to Robertsonian Translocation and 1% due to Down mosaicism (no maternal association).
(3) Results of Pregnancy quad screen: Decreased alpha-fetoprotein, Increased beta-hCG, Decreased estriol, and increased inhibin A.
(4) Ultrasound shows Increased nuchal translucency.

Front 37

Edward's Syndrome

Back 37

Defect:
--Trisomy 18

Symptoms:
(1) Severe mental retardation
(2) Rocker-bottom feet
(3) MICROGNATHIA (small jaw)
(4) Low-set ears
(5) Prominent occiput
(6) CLENCHED HANDS
(7) Congenital heart disease

NOTES:
--Death usually in 1st year of birth.
--2nd most common life birth trisomy after Down syndrome.

Front 38

Patau's Syndrome

Back 38

Defect:
--Trisomy 13

Symptoms:
(1) Severe mental retardation
(2) Rocker-bottom feet
(3) microphthalmia
(4) Microcephaly
(5) CLEFT LIP/PALATE
(6) HOLOPROSENCEPHALY
(7) Polydactyly

NOTES:
--Death usually in 1st year of birth.

Front 39

Cri-du-chat syndrome

Back 39

Defect:
--Congenital microdeletion of short arm chromosome 5 (46, xx or xy 5p-)

Symptoms:
(1) Microcephaly
(2) moderate to severe mental retardation
(3) high-pitched crying/mewing
(4) epicanthal folds
(5) cardiac abnormalities

NOTES:
--Cri du chat = cry of the cat (meow meow).

Front 40

Williams Syndrome

Back 40

Defect:
--Congenital microdeletion of long arm chromosome 7 (deleted region includes elatin gene).


Symptoms:
(1) distinctive "elfin" facies
(2) Mental retardation
(3) hypercalcemia (increased sensitivity to vitamin D).
(4) Well-developed veral skills
(5) extreme friendliness with strangers.
(6) Cardiovascular problems.

NOTES:

Front 41

DiGeorge Syndrome

Back 41

--1 of 2 the 22q11 deletion syndromes.

Defect: Microdeletion at chromosome 22q11

Symptoms:
(1) Cleft Palate
(2) Abnormal facies
(3) Thymic aplasia--> T-cell deficiency
(4) Cardiac defects
(5) Hypocalcemia secondary to parathyroid aplasia, due to microdeletion at chromosome 22q11.

NOTES:

Front 42

Velocardiofacial Syndrome

Back 42

--1 of the 2 22q11 deletion syndromes.

Defect: Microdeletion at chromosome 22q11.

Symptoms:
(1) Palate, facial, and cardiac defects.



NOTES:
--Compare to DiGeorge Syndrome

Front 43

Torsades de Pointes

Back 43

Defect: Anything that prolongs the QT interval can predispose you to this.

Symptoms:
--Ventricular tachycardia, characterized by shifting sinusoidal waveforms on ECG. --Can Progress to V-fib.
--Congenital long QT syndromes are most often due to defects in cardiac sodium or potassium channels.
--Can present with severe congenital sensorineural deafness (Jervell and Lange-Nielsen syndrome).


NOTES:

Front 44

Heart Murmurs--
Mitral Regurgitation

Back 44

--Holosystolic, high-pitched "blowing murmur."
--Mitral— loudest at apex and radiates toward axilla.
--Enhanced by maneuvers that Increase TPR (e.g., squatting, hand grip) or LA return
(e.g., expiration).
--MR is often due to ischemic heart disease, mitral valve prolapse, or LV dilation.

Front 45

Heart Murmurs -- Tricuspid Regurgitation

Back 45

--Tricuspid—loudest at tricuspid area and radiates to right
sternal border.
--Enhanced by maneuvers that Increase RA return (e.g., inspiration). TR is due to RV dilation or endocarditis. --Rheumatic fever can cause both.

Front 46

Heart Murmurs--Aortic Stenosis (AS)

Back 46

--Crescendo-decrescendo systolic ejection murmur following ejection click (EC; due to abrupt halting of valve leaflets).
--LV >> aortic pressure during systole. Radiates to carotids/apex.
--"Pulsus parvus et tardus" pulses weak compared to heart sounds.
--Can lead to syncope. Often due to age-related calcific
aortic stenosis or bicuspid aortic valve.
--Can also lead to hemolytic anemia w/ schistocytes and hemoglobinuria.

Front 47

Heart Murmurs-- VSD

Back 47

--Holosystolic, harsh-sounding murmur. Loudest at tricuspid area.
--Might suspect in baby who has failure to thrive and becomes sweaty and tachypnic when feeding few weeks to months after birth.

Front 48

Heart Murmurs-- Mitral Prolapse

Back 48

--Late systolic crescendo murmur with midsystolic click (MC; due MC to sudden tensing of chordae tendineae).
--Most frequent valvular lesion. --Loudest at S2. Usually benign. --Can predispose to infective endocarditis.
--Can be caused by myxomatous degeneration, rheumatic fever, or chordae rupture.
--Enhanced by maneuvers that Increase TPR (e.g., squatting, hand grip).

Front 49

Heart Murmurs-- Aortic Regurgitation (AR)

Back 49

--Immediate high-pitched "blowing" diastolic murmur.
--Wide pulse pressure when chronic; can present with bounding pulses and
head bobbing.
--Often due to aortic root dilation, bicuspid aortic
valve, or rheumatic fever. --Vasodilators intensity of murmur.

Front 50

Heart Murmurs-- Mitral Stenosis (MS)

Back 50

--Follows opening snap (OS; due to tensing of chordae tendineae).
--Delayed rumbling late diastolic murmur. LA >> LV pressure
during diastole. Often occurs 2° to rheumatic fever.
--Chronic MS can result in LA dilation. Enhanced by maneuvers that increase LA
return (e.g., expiration).

Front 51

Heart Murmurs-- Patent Ductus Arteriosis (PDA)

Back 51

--Continuous machine-like murmur. Loudest at S2.
--Often due to
congenital rubella or prematurity.

Front 52

Wolff-Parkinson-White Syndrome

Back 52

Also known as ventricular preexcitation syndrome.
Defect:
--Accessory conduction pathway from atria to ventricle (bundle of Kent), bypassing AV node. As a result, ventricles begin to
partially depolarize earlier, giving rise to characteristic delta wave on ECG.
--May result in 6 wave reentry current leading to supraventricular tachycardia.
Symptoms:

NOTES:
--DO NOT use beta-blockers or ca2+ channel blockers --> Increase AV node refractory state and forces tachyarrhthymia down accessory pathway.

Front 53

Atrial Fibrillation

Back 53

Defect:
--Chaotic and erratic baseline (irregularly irregular) with no discrete P waves in between
irregularly spaced QRS complexes.
--Can result in atrial stasis and lead to stroke.

Symptoms:


NOTES:
--Treat with beta-blocker or calcium channel blocker.
--prophylaxis against thromboembolism with warfarin (Coumadin).

Front 54

Atrial Flutter

Back 54

--A rapid succession of identical, back-to-back atrial depolarization waves.
--The identical appearance accounts for the "sawtooth" appearance of the flutter waves.



NOTES:
--Attempt to convert to sinus rhythm. Use class IA, IC or III antiarrhythmics.

Front 55

AV block --1st degree

Back 55

--The PR interval is prolonged (> 200 msec).
--Asymptomatic thus USUALLY DONT treat.

Front 56

AV blocks-- 2nd degree

Back 56

I) Mobitz type I (Wenckebach)

--Progressive lengthening of the PR interval until a beat is "dropped" (a P wave not
followed by a QRS complex). --Usually asymptomatic.

II) Mobitz type II

--Dropped beats that are not preceded by a change in the length of the PR interval (as in
type I).
--These abrupt, nonconducted P waves result in a pathologic condition.
--It is often found as 2:1 block, where there are 2 P waves to 1 QRS response. May progress to 3rd degree block.

Front 57

AV Node block -- 3rd degree (complete)

Back 57

--The atria and ventricles beat independently of each other. --Both P waves and QRS
complexes are present, although the P WAVES BEAR NO RELATION TO QRS COMPLEXES.
--The atrial rate is faster than the ventricular rate. Usually treated with pacemaker.
--Lyme disease can result in 3rd-degree heart block.

Front 58

Ventricular Fibrillation

Back 58

--A completely erratic rhythm with no identifiable waves.
--Fatal arrhythmia without
fibrillation immediate CPR and defibrillation.

Front 59

Tetralogy of Fallot (Most common cause of early cyanosis)

Back 59

DEFECT:
Anterosuperior displacement of the infundibular septum. PATHOLOGY:
--Pulmonary Stenosis (most important determinant for prognosis)
--RVH --Overriding aorta (overrides the VSD) --VSD
SYMPTOMS
--Early cyanosis caused by right-to-left shunt across the VSD.
--Right to left shunt due to increased pressure caused by stenotic pulmonic valve.
--On x-ray, boot-shaped heart due to RVH. --Patient suffer "cyanotic spells"

NOTES:
--Patient squat to improve symptoms: compression of femoral arteries increases TPR thus decreasing the right-to-left shunt and directing more blood from the RV to lungs.
--Compression--> resistance--> pressure

Front 60

Eisenmenger's syndrome

Back 60

--Uncorrected VSD, ASD, or PDA causes compensatory
vascular hypertrophy, which results in progressive
pulmonary hypertension.
-- As pulmonary resistance
Increases, the shunt reverses from L —> R to R--> L, which
causes late cyanosis (clubbing and polycythemia).

Front 61

D-Transposition of Great Vessels

Back 61

Defect:
--Due to failure of the aorticopulmonary septum to spiral


Symptoms:
--RV--> Aorta
--LV-->Pulmonary Trunk
--Both cause separation of systemic and pulmonary circulations (no mixing).


NOTES:
--NOT compatible with life unless shunt is present to mix the blood (e.g. VSD, PDA, or patent foramen ovale).
--W/O surgical correction, most infants die in first month of life.

Front 62

Coarctation of the aorta

Back 62

INFANTILE TYPE:
--preductal aortic stenosis
--Associated with Turner Syndrome.
--Check femoral pulses on physical exam (upper extremity pressure > lower extremity).

ADULT TYPE:
--Stenosis distal to ligamentum arteriosum (post-ductal).
--Associated with rib notching (due to collateral circulation)
--Hypertension in upper extremities and weak pulses in lower extremities.
--Can result in aortic regurgitation

Front 63

Patent ductus arteriosus

Back 63

--Fetus: Shunt is right to left (pulmonary trunk to aorta--normal)
--In neonatal, lung resistance decreases and shunt --> Left to right w/ subsequent RVH and failure (abnormal).
--Associated with continuous "machine-like" mumur.
--Patency maintained by PGE synthesis and low O2 tension.
--Uncorrected PDA can result in late cyanosis in lower extremities (differential cyanosis).

NOTES:
--Endomethacin (NSAIDS)-- Closes PDA
--Prostaglandings-- keep it open.
--Ductus arteriosus derived from 6th aortic arch.

Front 64

Hyperlipidemia signs

Back 64

-Atheromas--plaques in blood vessels.
--Xanthomas-- plaques or nodules composed of lipid-laden histiocytes in skin, especially eyelids (xanthelasma)

--Tendinous xanthoma--LIpid deposit in tendon, especially achilles

--Corneal arcus--Lipid deposit in cornea, non-specific (arcus senilis)

Front 65

Monckeberg Arteriosclerosis

Back 65

--1 of 3 arteriosclerosis

--Calcification in the media of the ARTERIES, especially radial or ulnar.
--Usually benign; "pipestem" arteries.
--Does NOT obstruct blood flow; intima not involved.

Front 66

Arteriolosclerosis arteriosclerosis

Back 66

--1 of 3 arteriosclerosis

--Hyaline thickening of small arteries in essential HTN or DM.
--Hyperplastic "onion skinning" in malignant HTN.

Front 67

Atherosclerosis - arteriosclerosis

Back 67

--1 of 3 arteriosclerosis
--Fibrous plaques and atheromas form in intima of arteries.

Front 68

Aortic Dissection

Back 68

--Longitudinal intraluminal tear forming a false lumen
--Associated with HTN or cystic medial necrosis (component of Marfan's syndrome).

Symptoms/exam:
--Tearing chest pain radiating to the back.
--CXR--mediastinal widening
--The false lumen occupies most of the descending aorta.
--Can result in aortic rupture and death.

Front 69

Ischemic Heart Disease

Back 69

Possible Manifestation:
1) Angina (CAD narrowing>75%)
--Stable --mostly 2ary to atherosclerosis; ST depression on ECG (retrosternal chest pain with exertion)
--Prinzmetal's variant--occurs at rest 2ary to coronary artery spasm; ST elevation on ECG.
--Unstable/crescendo- thrombosis but necrosis; ST depression on ECG (worsening chest pain at rest or with minimal exertion).
2) MI- most often due to coronary artery atherosclerosis; results in myocyte necrosis.
3) Sudden cardiac death-- death from cardiac causes w/ in 1 hour of onset of symptoms, most commonly letal arrhythmia (eg. V-fib).
4) Chronic ischemic heart disease- progressive onset of CHF over many years due to chronic ischemic myocardial damage.

Front 70

Evolution of MI

Back 70

Coronary artery occlusion: LAD > RCA > circumflex.
Symptoms: diaphoresis, nausea, vomiting, severe retrosternal pain, pain in left arm and/or jaw, SOB, fatigue, and adrenergic symp.

Day 1: Risk of arrhythmia


Day 2-4:


Day 5-10:


7 weeks:

Front 71

Diagnosis of MI

Back 71

--1st 6 hours, ECG is the GOLD STANDARD.
Cardiac troponin I-- rises after 4 hours and is elevated
for 7-10 days; more specific than other protein
markers.
--CK-MB is predominantly found in myocardium but
can also be released from skeletal muscle. Useful
in diagnosing reinfarction on top of acute MI.
--AST is nonspecific and can be found in cardiac, liver,
and skeletal muscle cells.
--ECG changes can include ST elevation (transmural
infarct), ST depression (subendocardial infarct),
and pathologic Q waves (transmural infarct).

Front 72

Types of Infarcts: Transmural vs. subendocardial infarcts.

Back 72

--Transmural infarcts:
(1)Increased necrosis
(2) Affects entire wall
(3) ST elevation on ECG
(4) Q waves

--Subendocardial infarcts
(1) Due to ischemic necrosis of <50% of ventricle wall.
(2) Subendocardium especially vulnerable to ischemia.
(3) Due to fewer collaterals, higher pressure
(4) ST depression on ECG

Front 73

ECG diagnosis of MI

Back 73

Infarct location Leads with Q waves
Anterior wall (LAD) V1—V4
Anteroseptal (LAD) V1—V2
Anterolateral (LCX) V4—V6
Lateral wall (LCX) I, aVL
Inferior wall (RCA) II, III, aVF

Front 74

MI complications

Back 74

1. Cardiac arrhythmia—Can lead to death before reaching hospital; common in first few days
2. LV failure and pulmonary edema
3. Cardiogenic shock (large infarct—high risk of mortality)
4. Ventricular free wall rupture cardiac tamponade; papillary muscle rupture severe
mitral regurgitation; and interventricular septal rupture —> VSD
5. Aneurysm formation—si, CO, risk of arrhythmia, embolus from mural thrombus
6. Postinfarction fibrinous pericarditis—friction rub (3-5 days post-MI)
7. Dressler's syndrome— autoimmune phenomenon resulting in fibrinous pericarditis (several weeks post-MI)

Front 75

Dilated (congestive) Cardiomyopathy

Back 75

--1 of 3 cardiomyopathies (other: hypertrophic and restrictive/obliterative)
--Most common cardiomyopathy (90% of cases).
--Etiologies include chronic Alcohol abuse, wet Beriberi, Coxsackie B virus myocarditis, chronic Cocaine use, Chagas' disease, Doxorubicin toxicity, hemochromatosis, and peripartum cardiomyopathy.

--Findings: S3, dilated heart on ultrasound, balloon appearance on chest x-ray.

NOTES: --Systolic dysfunction ensues.
--Eccentric hypertrophy (sarcomeres added in series).

Front 76

Hypertrophic Cardiomyopathy

Back 76

--1 of 3 cardiomyopathies (other: Dilated and restrictive/obliterative)
--Hypertrophied IV septum --> "too close" to mitral
valve leaflet, leading to outflow tract obstruction.
--50% of cases are familial, autosomal dominant.
--Associated with Friedreich's ataxia. Disoriented,
tangled, hypertrophied myocardial fibers.
--Cause of sudden death in young athletes.
--Findings: normal-sized heart, S4, apical impulses,
systolic murmur.
Treat with Beta-blocker or
non-dihydropyridine calcium channel blocker (e.g., verapamil).
NOTES: --Diastolic dysfunction ensues.
--Concentric hypertrophy (sarcomeres added in
parallel).
--Proximity of hypertrophied IV septum to mitral leaflet
obstructs outflow tract, resulting in systolic murmur
and syncopal episodes.

Front 77

Restrictive/obliterative cardiomyopathy

Back 77

--Major causes include sarcoidosis, amyloidosis,
cardiomyopathy postradiation fibrosis, endocardial fibroelastosis (thick fibroelastic tissue in endocardium of
young children), Loffler's syndrome
(endomyocardial fibrosis with a prominent
eosinophilic infilitrate), and hemochromatosis
(dilated cardiomyopathy can also occur).

NOTES: Diastolic dysfunction ensues.

Front 78

Libman-Sacks endocarditis

Back 78

--Verrucous (wartlike), sterile vegetations occur on both sides of the valve.
--Most often benign; can
be associated with mitral regurgitation and, less
commonly, mitral stenosis.

NOTES:
--SLE causes LSE

Front 79

Rheumatic heart disease

Back 79

--Post pharyngeal infection with
group A beta-hemolytic streptococci.
--Early deaths due to myocarditis.
--Late sequelae include rheumatic heart disease, which
affects heart valves—mitral > aortic >>
tricuspid (high-pressure valves affected most).
--Early lesion is mitral valve prolapse; late
lesion is mitral stenosis.
--Associated with Aschoff bodies, Anitschkow's cells (activated histiocytes), elevated ASO titers.

NOTES: --Immune mediated (type II hypersensitivity); not
direct effect of bacteria.
--Antibodies to M protein.
--FEVERSS: Fever, Erythema marginatum, Valvular damage (vegetation and fibrosis), ESR, Red-hot joints (migratory
polyarthritis), Subcutaneous nodules, Aschoff body St. Vitus' dance (chorea)

Front 80

Cardiac Tamponade

Back 80

--Compression of heart by fluid (e.g., blood, effusions) in pericardium, leading to decreased CO.
--Equilibration of diastolic pressures in all 4 chambers.

--Findings: hypotension, Increased venous pressure (JVD), distant heart sounds, Increased HR, pulsus paradoxus.

NOTES:
--Pulsus paradoxus (Kussmaul's pulse) — exaggerated in amplitude of pulse during inspiration. Seen in severe cardiac tamponade, asthma, obstructive sleep apnea,
pericarditis, and croup.

Front 81

Syphilitic Heart Disease

Back 81

--3° syphilis disrupts the vasa vasorum of the aorta w/ dilation of aorta and valve ring.
--Can result in aneurysm of ascending aorta or aortic valve incompetence.
--May see calcification of the aortic root and ascending arch. Leads to "tree bark" appearance of the incompetence.
aorta.

Front 82

Cardiac Tumors

Back 82

--Most common primary tumor in ADULTS: Myxomas
--90% occur in the atria (mostly left atrium).
--Myxomas are usually described as a "ball-valve" obstruction in the left atrium (associated with multiple syncopal episodes).
--Most common primary tumor in CHILDREN: Rhabdomyomas (associated with tuberous sclerosis).
Kussmaul's sign: Increased in jugular venous pressure on inspiration.

Front 83

Varicose Veins

Back 83

--Dilated, tortuous superficial veins due to chronically increased
venous pressure.
--Predisposes to poor wound healing and varicose ulcers.


NOTES:
--Thromboembolism is rare (compare with stasis of deep veins).

Front 84

Raynaud's Disease

Back 84

--Decreased blood flow to the skin due to arteriolar vasospasm w/ cold temperature or emotional stress.
--Most often in fingers and toes.
--COMPARE with Raynaud's phenomenon when 2ary to a mixed CT disease, SLE, or CREST syndrome.

Front 85

Wegener's Granulomatosis

Back 85

Triad:
--focal necrotizing vasculitis
--necrotizing granulomas in the LUNG AND UPPER AIRWAY
--necrotizing glomerulonephritis (type III pauci immune rapidly progressing glomerulonephritis.)
Symptoms:
--Hemoptysis, hematuria, perforation of nasal septum, chronic sinusitis, otitis media, mastoiditis, cough, dyspnea.
Findings:
-c-ANCA = strong marker of disease.
-chest x-ray may show large nodular densities.
-hematuria and red cell casts.
TX:
-Cyclophosphamide and corticosteroids.

Front 86

Sturge-Weber disease

Back 86

--Congenital vascular disorder that affects capillary sized
blood vessels.
--Manifests with (1) port-wine stain (aka nevus flammeus) on face, (2) ipsilateral leptomeningeal angiomatosis (intracerebral AVM), (3) seizures, and early-onset glaucoma.

NOTES:
--Affects small vessels, but is not a vasculitis.

Front 87

Henoch-Schonlein purpura

Back 87

--Most common form of childhood systemic vasculitis.

Symptoms:
(1) Skin rash on buttocks and legs (palpable purpura)
(2) arthralgia (3) intestinal hemorrhage (4) abdominal pain and (5) melena.

NOTES:
--Follows URIs.
--IgA immune complexes
--Association with IgA nephropathy.
--Palpable purpura-- due to immune complex deposition in walls of BVs and complement activation.

Front 88

Buerger's Disease

Back 88

--AKA-- thromboangiitis obliterans;
idiopathic, segmental, thrombosing vasculitis of small and medium peripheral arteries and veins.
--Seen in HEAVY SMOKERS.
Symptoms:
(1) Intermittent claudication, (2) superficial nodular
phlebitis, (3) cold sensitivity (Raynaud's phenomenon),
severe pain in affected part. May lead to gangrene
and autoamputation of digits.

Tx: Smoking cessation.
NOTES: --Affects small and medium vessels.
--Medium-vessel diseases cause thrombosis/infarction of arteries.

Front 89

Kawasaki Disease

Back 89

--Acute, self-limiting necrotizing vasculitis in infants/children. --Association with Asian ethnicity.

Symptoms:
--Fever --conjunctivitis --changes in lips/oral mucosa
("strawberry tongue") --lymphadenitis --desquamative
skin rash.
--MAY DEVELOP CORONARY ANEURYSMS.

TX: IV immunoglobulin, aspirin.
NOTES:
--Affects small and medium vessels.

Front 90

Polyarteritis nodosa

Back 90

--Immune complex–mediated transmural vasculitis
with fibrinoid necrosis.
Symptoms:
Fever, weight loss, malaise, abdominal pain, melena,
headache, myalgia, hypertension, neurologic
dysfunction, cutaneous eruptions.
FIndings:
--HEPATITIS B seropositivity in 30% of patients.
--Multiple aneurysms and constrictions on arteriogram.
Tx: Corticosteroids, cyclophosphamide.
NOTES: --Affects small and medium arteries.
--Involves renal and visceral vessels, NOT pulmonary arteries.

Front 91

Takayasu's arteritis

Back 91

AKA-- "PULSELESS DISEASE"— granulomatous
thickening of aortic arch and/or proximal great
vessels.
--Associated with an increased ESR.
--Primarily affects Asian females < 40 years of age.
Symptoms:
Fever, Arthritis, Night sweats, MYalgia, SKIN
nodules, Ocular disturbances, Weak pulses in
upper extremities.

NOTES: affects medium and large arteries.

Front 92

Temporal arteritis (Giant cell arteritis)

Back 92

--Most common vasculitis affecting medium and
large arteries, usually branches of carotid artery.
--Focal, granulomatous inflammation. --Affects elderly females.
Symptoms:
--Unilateral headache, jaw claudication, impaired
vision (occlusion of ophthalmic artery that may
lead to irreversible blindness).
Findings:
--Associated with an increased ESR. 1/2 of pts -->systemic involvement and polymyalgia rheumatica (stiff shoulder).
TX: High-dose steroids.
NOTES: --Affects medium and large arteries

Front 93

Strawberry hemangioma

Back 93

--Benign capillary hemangioma of infancy.
--Initially grows with child; then spontaneously regresses.

Front 94

Cherry hemangioma

Back 94

Benign capillary hemangioma of the elderly.
--Does not regress. Frequency
Increases with age.

Front 95

Pyogenic granuloma

Back 95

--Polypoid capillary hemangioma that can ulcerate and bleed.
--Associated with trauma and pregnancy.

Front 96

Cystic hygroma

Back 96

--Cavernous lymphangioma of the neck.
--Associated with Turner syndrome.

Front 97

Glomus tumor

Back 97

--Benign, painful, red-blue tumor under fingernails.
--Arises from modified
smooth muscle cells of glomus body.

Front 98

Bacillary angiomatosis

Back 98

--Benign capillary skin papules found in AIDS patients.
--Caused by Bartonella
henselae infections.
-- Frequently mistaken for Kaposi's sarcoma.

Front 99

Angiosarcoma

Back 99

--Highly lethal malignancy of the liver.
--Associated with vinyl chloride, arsenic, and Th02 (Thorotrast) exposure.

Front 100

Lymphangiosarcoma

Back 100

--Lymphatic malignancy associated with persistent lymphedema (e.g., post—radical mastectomy)

Front 101

Kaposi's sarcoma

Back 101

--Endothelial malignancy of the skin associated with HHV-8 and HIV.
--Frequently mistaken for bacillary angiomatosis.

Front 102

Hydralazine

Back 102

--Mechanism:
Increased cGMP —> smooth muscle relaxation. Vasodilates arterioles > veins; afterload reduction.

--Clinical Use:
Severe hypertension, CHF. First-line therapy for hypertension in pregnancy, with methyldopa. Frequently coadministered with a beta-blocker to prevent reflex tachycardia.

--Toxicity
Compensatory tachycardia (contraindicated in angina/CAD), fluid retention, nausea, headache, angina. Lupus-like syndrome.

Front 103

Calcium channel
blockers

Back 103

Nifedipine, verapamil, diltiazem.
--Mechanism:
Block voltage-dependent L-type calcium channels of cardiac and smooth muscle and thereby reduce muscle contractility.
Vascular smooth muscle—nifedipine > diltiazem > verapamil (Verapamil = Ventricle).
Heart—verapamil > diltiazem > nifedipine.
--Clinical Use
Hypertension, angina, arrhythmias (not nifedipine), Prinzmetal's angina, Raynaud's.
--Toxicity
Cardiac depression, AV block, peripheral edema, flushing, dizziness, and constipation.

Front 104

Nitroglycerin, isosorbide dinitrate

Back 104

--Mechanism:
Increase nitric oxide in smooth muscle (vasodilate), causing increase in cGMP --> smooth muscle relaxation (due to decrease in Ca+).
--Dilate veins >> arteries. preload.

Clinical use: Angina, pulmonary edema. Also used as an aphrodisiac and erection enhancer.
Toxicity:
Reflex tachycardia, hypotension, flushing, headache, "Monday disease" in industrial exposure; development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend, resulting in tachycardia, dizziness, and headache on reexposure.

Front 105

Malignant Hypertension Treatment

Back 105

Nitroprusside--Short acting; Increase cGMP via direct release of NO. Can cause cyanide toxicity (releases CN).

Fenoldopam--Dopamine D1 receptor agonist— relaxes renal vascular smooth muscle.

Diazoxide--K+ channel opener—hyperpolarizes and relaxes vascular smooth muscle. Can cause hyperglycemia (reduces insulin release).

Front 106

HMC-CoA reductase
inhibitors (lovastatin,
pravastatin, simvastatin,
atorvastatin, rosuvastatin)

Back 106

NT

Front 107

Niacin

Back 107

NT

Front 108

Bile acid resins
(cholestyramine,
colestipol, colesevelam)

Back 108

NT

Front 109

Cholesterol absorption
blockers (ezetimibe)

Back 109

NT

Front 110

"Fibrates" (gemfibrozil,
clofibrate, bezafibrate,
fenofibrate)

Back 110

NT

Front 111

Quinidine

Back 111

Class IA Antiarrhythmics

--Increased AP duration
--Increased effective refractory period (ERP), increased QT interval.
--Affect both atrial and ventricular
arrhythmias, especially reentrant and ectopic
supraventricular and ventricular tachycardia.
--Toxicity:
quinidine (cinchonism— headache, tinnitus);
thrombocytopenia; torsades de pointer due to T
QT interval; procainamide (reversible SLE-like
syndrome).

Front 112

Procainamide

Back 112

Class IA Antiarrhythmics

--Increased AP duration
--Increased effective refractory period (ERP), increased QT interval.
--Affect both atrial and ventricular
arrhythmias, especially reentrant and ectopic
supraventricular and ventricular tachycardia
--Toxicity:
quinidine (cinchonism— headache, tinnitus);
thrombocytopenia; torsades de pointer due to T
QT interval; procainamide (reversible SLE-like
syndrome).

Front 113

Disopyramide

Back 113

Class IA Antiarrhythmics

--Increased AP duration
--Increased effective refractory period (ERP), increased QT interval.
--Affect both atrial and ventricular
arrhythmias, especially reentrant and ectopic
supraventricular and ventricular tachycardia
--Toxicity:
quinidine (cinchonism— headache, tinnitus);
thrombocytopenia; torsades de pointer due to T
QT interval; procainamide (reversible SLE-like
syndrome).

Front 114

Lidocaine

Back 114

--Class 1B Antiarrhythmics
--Decreased AP duration.
--Preferentially affect ischemic or depolarized Purkinje and ventricular tissue.
--Useful in acute ventricular arrhythmias (especially post-MI) and in
digitalis-induced arrhythmias.

Toxicity: local anesthetic. CNS stimulation/depression,
cardiovascular depression.
NOTES:
Phenytoin can also fall into the 1B category.

Front 115

Mexiletine

Back 115

--Class 1B Antiarrhythmics
--Decreased AP duration.
--Preferentially affect ischemic or depolarized Purkinje and ventricular tissue.
--Useful in acute ventricular arrhythmias (especially post-MI) and in
digitalis-induced arrhythmias.

Toxicity: local anesthetic. CNS stimulation/depression,
cardiovascular depression.
NOTES:
Phenytoin can also fall into the 1B category.

Front 116

Tocainide

Back 116

--Class 1B Antiarrhythmics
--Decreased AP duration.
--Preferentially affect ischemic or depolarized Purkinje and ventricular tissue.
--Useful in acute ventricular arrhythmias (especially post-MI) and in
digitalis-induced arrhythmias.

Toxicity: local anesthetic. CNS stimulation/depression,
cardiovascular depression.
NOTES:
Phenytoin can also fall into the 1B category.

Front 117

Flecainide

Back 117

--No effect on AP duration.
--Useful in V-tachs that progress to VF and in intractable SVT.
--Usually used only as last resort in refractory tachyarrhythmias.
--For patients without structural abnormalities.

Toxicity:
--proarrhythmic, especially post-MI (contraindicated)
--Significantly prolongs refractory period in AV node.

Front 118

Encainide

Back 118

--No effect on AP duration.
--Useful in V-tachs that progress to VF and in intractable SVT.
--Usually used only as last resort in refractory tachyarrhythmias.
--For patients without structural abnormalities.

Toxicity:
--proarrhythmic, especially post-MI (contraindicated)
--Significantly prolongs refractory period in AV node.

Front 119

Propafenone

Back 119

--No effect on AP duration.
--Useful in V-tachs that progress to VF and in intractable SVT.
--Usually used only as last resort in refractory tachyarrhythmias.
--For patients without structural abnormalities.

Toxicity:
--proarrhythmic, especially post-MI (contraindicated)
--Significantly prolongs refractory period in AV node.

Front 120

Anti-arrhythmics (class II)
--Beta blockers --ALL OF THEM

Back 120

Mechanism:
--Decreased cAMP and Ca2+ currents. Suppress abnormal pacemakers by decreasing slope of phase 4.
--AV node particularly sensitive— Increased PR interval. Esmolol very short acting.
Clinical use: V-tach, SVT, slowing ventricular rate during atrial fibrillation and atrial flutter.
Toxicity:
--Impotence, exacerbation of asthma, cardiovascular effects (bradycardia, AV block, CHF), CNS effects (sedation, sleep alterations).
--May mask the signs of hypoglycemia.
--Metoprolol can cause dyslipidemia.
--Treat overdose with glucagon.

Front 121

Sotalol

Back 121

Mechanism:
--Increased AP duration, Increased ERP. Used when other
antiarrhythmics fail. Increased QT interval.

Toxicity
Sotalol—torsades de pointes, excessive beta block;
ibutilide—torsades; bretylium—new arrhythmias,
hypotension; amiodarone —PULMONARY FIBROSIS, HEPATOTOXICITY, HYPOTHYROIDISM/HYPERTHYROIDISM
(amiodarone is 40% iodine by weight), corneal
deposits, skin deposits (blue/gray) resulting in
photodermatitis, neurologic effects, constipation,
cardiovascular effects (bradycardia, heart block,
CHF).
Amiodarone has class I, II, III, and IV effects because it alters the lipid membrane.

Front 122

Ibutilide

Back 122

Mechanism:
--Increased AP duration, Increased ERP. Used when other
antiarrhythmics fail. Increased QT interval.

Toxicity
Sotalol—torsades de pointes, excessive beta block;
ibutilide—torsades; bretylium—new arrhythmias,
hypotension; amiodarone —PULMONARY FIBROSIS, HEPATOTOXICITY, HYPOTHYROIDISM/HYPERTHYROIDISM
(amiodarone is 40% iodine by weight), corneal
deposits, skin deposits (blue/gray) resulting in
photodermatitis, neurologic effects, constipation,
cardiovascular effects (bradycardia, heart block,
CHF).
Amiodarone has class I, II, III, and IV effects because it alters the lipid membrane.

Front 123

Bretylium

Back 123

Mechanism:
--Increased AP duration, Increased ERP. Used when other
antiarrhythmics fail. Increased QT interval.

Toxicity
Sotalol—torsades de pointes, excessive beta block;
ibutilide—torsades; bretylium—new arrhythmias,
hypotension; amiodarone —PULMONARY FIBROSIS, HEPATOTOXICITY, HYPOTHYROIDISM/HYPERTHYROIDISM
(amiodarone is 40% iodine by weight), corneal
deposits, skin deposits (blue/gray) resulting in
photodermatitis, neurologic effects, constipation,
cardiovascular effects (bradycardia, heart block,
CHF).
Amiodarone has class I, II, III, and IV effects because it alters the lipid membrane.

Front 124

Dofetilide

Back 124

Mechanism:
--Increased AP duration, Increased ERP. Used when other
antiarrhythmics fail. Increased QT interval.

Toxicity
Sotalol—torsades de pointes, excessive beta block;
ibutilide—torsades; bretylium—new arrhythmias,
hypotension; amiodarone —PULMONARY FIBROSIS, HEPATOTOXICITY, HYPOTHYROIDISM/HYPERTHYROIDISM
(amiodarone is 40% iodine by weight), corneal
deposits, skin deposits (blue/gray) resulting in
photodermatitis, neurologic effects, constipation,
cardiovascular effects (bradycardia, heart block,
CHF).
Amiodarone has class I, II, III, and IV effects because it alters the lipid membrane.

Front 125

Amiodarone

Back 125

Mechanism:
--Increased AP duration, Increased ERP. Used when other
antiarrhythmics fail. Increased QT interval.

Toxicity
Sotalol—torsades de pointes, excessive beta block;
ibutilide—torsades; bretylium—new arrhythmias,
hypotension; amiodarone —PULMONARY FIBROSIS, HEPATOTOXICITY, HYPOTHYROIDISM/HYPERTHYROIDISM
(amiodarone is 40% iodine by weight), corneal
deposits, skin deposits (blue/gray) resulting in
photodermatitis, neurologic effects, constipation,
cardiovascular effects (bradycardia, heart block,
CHF).
Amiodarone has class I, II, III, and IV effects because it alters the lipid membrane.

Front 126

Verapamil

Back 126

Class IV antiarrhythmic Ca2+ blocker
Mechanism:
--conduction velocity, Increased ERP, Increased PR interval.
--Used in prevention of nodal arrhythmias (e.g., SVT).

Toxicity:
--Constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression).

Front 127

diltiazem

Back 127

Class IV antiarrhythmic Ca2+ blocker
Mechanism:
--conduction velocity, Increased ERP, Increased PR interval.
--Used in prevention of nodal arrhythmias (e.g., SVT).

Toxicity:
--Constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression).

Front 128

Adenosine (antiarrhythmic)

Back 128

Increases K+ out of cells —> hyperpolarizing the cell + Decreases Ica.
-- Drug of choice in diagnosing/
abolishing supraventricular tachycardia. Very short acting (— 15 sec).
Toxicity:
--includes flushing, hypotension, chest pain. Effects blocked by theophylline.

Front 129

K+ (antiarrhythmic)

Back 129

Depresses ectopic pacemakers in hypokalemia (e.g., digoxin toxicity).

Front 130

mg2+ (antiarrhythmic)

Back 130

Effective in torsades de pointes and digoxin toxicity.

Front 131

Case-control study

Back 131

--Observational and retrospective
--Compares a group of people with disease to a group without.
Looks for prior exposure or risk factor. Asks, "What happened?"

Front 132

Cohort study

Back 132

--Observational and prospective
--Compares a group with a given exposure or
risk factor to a group without.
--Looks to see if exposure I the likelihood of disease.
Asks, "What will happen?"

Front 133

Cross-sectional study

Back 133

--Collects data from a group of people to assess
frequency of disease (and related risk factors) at a
particular point in time.
--Asks, "What is happening?"

Front 134

Twin concordance
study

Back 134

--Compares the frequency with which both monozygotic twins or both dizygotic twins develop a disease.
--Measures Hertability

Front 135

Adoption Study

Back 135

--Compares siblings raised by biologic vs. adoptive parents.
-- Measures heritability and influence of environmental factors.

Front 136

Clinical Trial Phase I

Back 136

--Experimental study involving humans. Compares therapeutic benefits of 2 or more
treatments, or of treatment and placebo. Highest-quality study when randomized,
controlled, and double-blinded (i.e., neither patient nor doctor knows if the patient
is in the treatment or control group).

Phase I-- Study sample is mall number of patients, usually healthy volunteers.

Purpose: Assesses safety, toxicity, and pharmacokinetics.

Front 137

Clinical Trial Phase II

Back 137

--Experimental study involving humans. Compares therapeutic benefits of 2 or more
treatments, or of treatment and placebo. Highest-quality study when randomized,
controlled, and double-blinded (i.e., neither patient nor doctor knows if the patient
is in the treatment or control group).

--STUDY SAMPLE: is small number of patients with disease of interest.
--PURPOSE: Assesses treatment efficacy, optimal dosing, and adverse effects.

Front 138

Clinical Trial Phase III

Back 138

--Experimental study involving humans. Compares therapeutic benefits of 2 or more
treatments, or of treatment and placebo. Highest-quality study when randomized,
controlled, and double-blinded (i.e., neither patient nor doctor knows if the patient
is in the treatment or control group).
--Study Sample: Large number of patients randomly assigned either to Tx under investigation or to best available treatment (or placebo).
PURPOSE: Compares the new treatment to the current standard of care.

Front 139

Clinical Trial Phase IV

Back 139

--Experimental study involving humans. Compares therapeutic benefits of 2 or more
treatments, or of treatment and placebo. Highest-quality study when randomized,
controlled, and double-blinded (i.e., neither patient nor doctor knows if the patient
is in the treatment or control group).
STUDY SAMPLE: Post marketing surveillance trial of patients after approval.
PURPOSE: Detects rare or long-term adverse effects.

Front 140

Meta-analysis

Back 140

--Pools data from several studies to come to an
overall conclusion. Achieves greater statistical individual studies or bias in
power and integrates results of similar studies.

--Highest echelon of clinical evidence.

NOTES: May be limited by quality of individual studies or bias in study selection.

Front 141

Sensitivity (biostats)

Back 141

--Proportion of all people with disease who test positive, or ability of a test to detect a disease when it is present.
--Value approaching 1 is desirable for ruling OUT disease and indicates a low false-negative rate.
--USES: for screning in diseases with low prevalence.
NOTES:
--Sensitivity = TP/(TP + FN)
--or sensitivity = 1 -- false-negative rate.
--If 100% sensitivity, sensitivity = 1, FN = 0 and all negatives must be true negatives (super awesome test).

Front 142

Specificity (biostats)

Back 142

--Proportion of all ppl w/o disease who test negative, or the ability of a test to indicate non-disease when disease is NOT present.
--Value closer to 1 is desirable for ruling IN disease and indicates a low false-positive rate.
--Uses: as a confirmatory test after a positive screening test.
NOTES:
Specificity = TN / (TN + FP)
Or Specificity = 1 — false-positive rate
Example: HIV testing. 1st screen with ELISA (sensitive, high false-positive rate, low threshold); confirm with western (specific, high false-negative rate, high threshold.)

Front 143

Positive Predictive Value (PPV)

Back 143

Proportion of positive test results that are true positive.
Probability that person actually has the disease
given a positive test result.
= TP / (TP + FP)
(Note: If the prevalence of a disease in a population
is low, even tests with high specificity or high
sensitivity will have low positive predictive values!)

NOTES:
PPV = TP / (TP + FP)

Front 144

Negative Predictive value (NPV)

Back 144

--Proportion of negative test results that are true negative.
--Probability that person actually is disease free given
a negative test result.

NOTES:
NPV= TN / (FN + TN)

Front 145

Prevalence vs. Incidence

Back 145

--Point prevalence = total cases in population at a given time / total population at a given time
--Incidence = new cases in population over a given period / Total population at risk during that period.
--Prevalence is approximately equal to (incidence x disease duration).
--Prevalence > incidence for chronic diseases (e.g.,
diabetes).
Prevalence = incidence for acute disease (e.g.,
common cold).
NOTES:
--Incidence is new incidents
--When calculating incidence, Dont forget to account for ppl currently w/ disease, or those previously positive for it, are not considered at risk.

Front 146

Odds ratio (OR) for case control studies

Back 146

--(Odds of having disease in exposed group) / (by odds of having disease in unexposed group)
--Approximates relative risk if prevalence of disease is not too high.

NOTES:
Odds ratio = (a/b)/(c/d)

Front 147

Relative RIsk (RR) for cohort studies

Back 147

--Relative probabilty of getting a disease in the exposed group compared to unexposed grou.
--Calculate as percent w/ disease in exposed group divided by percent w/ disease in unexposed group.

NOTES:
RR = (a/(a+b))/(c/(c+d))

Front 148

Attributable Risk

Back 148

--The difference in risk between exposed and unexposed groups, or the proportion of disease occurrences that are attributable to the exposure (e.g., smoking causes 1/3 of cases of pneumonia).

NOTES:
--Attributable risk = (a/a+b) -- (c/c+d)

Front 149

Absolute Risk reduction

Back 149

--The reduction in risk associated with a treatment as
compared to a placebo.

Front 150

Number Needed to Treat

Back 150

1/absolute risk reduction.

Front 151

Number needed to harm

Back 151

1/attributable risk.

Front 152

Precision vs. accuracy

Back 152

Precision is:
1. The consistency and reproducibility of a test
(reliability)
2. The absence of random variation in a test
Accuracy is the trueness of test measurements
(validity).

Notes:
--Random error-- reduced precision in a test.
--Systematic error--reduced accuracy in a test.

Front 153

Selection Bias

Back 153

nonrandom assignment to
study group (e.g., Berkson's bias)

Front 154

Recall Bias

Back 154

knowledge of presence of
disorder alters recall by subjects

Front 155

Sampling Bias

Back 155

--subjects are not representative relative to general population; therefore, results are not generalizable.

Front 156

Late-Look bias

Back 156

--information gathered at an
inappropriate time—e.g., using a survey to study
a fatal disease (only those patients still alive will
be able to answer survey)

Front 157

Procedure bias

Back 157

subjects in different groups are not treated the same—e.g., more attention
is paid to treatment group, stimulating greater
compliance

Front 158

Confounding bias

Back 158

occurs with 2 closely
associated factors; the effect of 1 factor distorts
or confuses the effect of the other

Front 159

Lead-time bias

Back 159

--early detection confused with increased survival; seen with improved screening (natural history of disease is not changed, but early detection makes it seem as though
survival increased)

Front 160

Pygmalion effect

Back 160

--occurs when a researcher's
belief in the efficacy of a treatment changes the outcome of that treatment

Front 161

Hawthorne effect

Back 161

occurs when the group being studied changes its behavior owing to the knowledge of being studied.

Front 162

Statistical Distribution (Normal distribution, positive skew, negative skew).

Back 162

--Normal = Gaussian = Bell-shaped (mean=media=mode)
--Bimodal is simply 2 humps (2 modal peaks)
Positive skew - Mean > Median > Mode. Asymmetry with tail on right.
Negative skew-- mean < median < mode. Asymmetry with tail on left.
NOTES:
--Mode is least affected by outliers in the sample.

Front 163

Statistical Hypotheses (Null hypothesis and Alternative)

Back 163

Null (Ho) = Hypothesis of no difference (e.g., there is no association between the disease and the risk factor in the population.)

Alternative (H1) = Hypothesis that there is some difference (e.g., there is some association between the disease and the risk factor in the population.)

Front 164

Type I error (alpha)

Back 164

--Stating that there IS an effect or difference when
none exists (to mistakenly accept the experimental
hypothesis and reject the null hypothesis). p =
probability of making a type I error. p is judged
against a preset level of significance (usually
< .05). "False-positive error."

Front 165

Type II Error (beta)

Back 165

--Stating that there is not an effect or difference when
one exists (to fail to reject the null hypothesis
when in fact Ho is false).
--beta is the probability of making a type II error.
"False-negative error."

NOTES:
Power = (1-beta)

Front 166

Power (1--beta)

Back 166

--Probability of rejecting null hypothesis when it is in
fact false, or the likelihood of finding a difference
if one in fact exists.
--It depends on:
(1) Total number of end points experienced by
population (2) Difference in compliance between
treatment groups (differences in the mean
values between groups) (3) Size of expected effect.

Notes:
--If you increase the sample size, you increase
power. There is power in
numbers.

Front 167

Standard deviation vs. standard error

Back 167

COPY from first aid pg. 54 since there be weird symbols.

Front 168

Confidence Interval

Back 168

--Range of values in which a specified probability
of the means of repeated samples would be expected to fall.
CI = range from [mean — Z(SEM)] to [mean + Z(SEM)].
The 95% CI (corresponding to p = .05) is often used. For the 95% CI, Z = 1.96.
NOTES:
--If the 95% CI for a mean difference between 2 variables includes 0, then there is no significant difference and Ho is not rejected. If the 95% CI for odds ratio or relative risk includes 1, Ho is not rejected.
--If the CI between 2 groups overlaps, then these groups are not significantly different.

Front 169

t-test vs. ANOVA vs. chi-squared ( )

Back 169

--t-test checks difference between the means of 2 groups.
--ANOVA checks difference between the means of 3 or more groups.
-- (chi-square) test checks difference between
2 or more percentages or proportions of
categorical outcomes (not mean values).

Front 170

Correlation coefficient (r)

Back 170

--r is always between —1 and +1. The closer the absolute value of r is to 1, the stronger the correlation between the 2 variables.
--Coefficient of determination = r2 (value that is usually reported).

Front 171

Disease Prevention (primary, secondary, and tertiary)

Back 171

1°—prevent disease occurrence (e.g., HPV
vaccination).
2° —early detection of disease (e.g., Pap smear).
3°—reduce disability from disease (e.g.,
chemotherapy).

NOTES:
PDR:
Prevent
Detect
Reduce disability

Front 172

Blood Groups

Back 172

A- A Antigen on RBC surface and B antibody in plasma.
B- B antigen on RBC surface and A antibody in plasma.
AB-- AB antigen on RBC surface; no antibodies in plasma; universal recipient.
O- Neither A nor B antigen on RBC surface; both antibodies in plasma. "UNIVERSAL DONOR"
Rh-- Rh antigen on RBC surface. Rh -- mothers exposed to fetal Rh+ blood may make anti-Rh IgG that can cross placenta in 2nd or subsequent pregnancies and cause hemolytic disease of new born (erythroblastosis fetalis) in fetus that is Rh+. Tx: Rh antigen immunoglobluin (Rhogam) for mother at 1st delivery to prevent future erythroblastosis.

Front 173

Coagulation, Complement, and Kinin pathways

Back 173

Look at Pg. 345

Front 174

Hemophilia A

Back 174

Deficiency of Factor VIII

Front 175

Hemophilia B

Back 175

Deficiency of factor IX

Front 176

Vitamin K deficiency

Back 176

Decreased synthesis of factors II, VII, IX, X, Protein C and S.

Front 177

Procoagulation vs. Anti-Coagulation components

Back 177

Look at Pg. 346

Front 178

Platelet Plug formation

Back 178

Look at Pg. 346 for diagram.

Front 179

Acanthocyte (spur cell)

Back 179

Associated Pathology:
Liver disease, abetalipoproteinemia

Front 180

Basophilic stippling

Back 180

Pathology:
--Thalassemias, Anemia of chronic disease, Iron deficiency, Lead poisoning.

Front 181

Bite Cell

Back 181

G6PD deficiency

Front 182

Elliptocyte

Back 182

Hereditary elliptocytosis

Front 183

Macro-Ovalocyte

Back 183

Pathology:
--Megaloblastic Anemia (also hypersegmented PMNs), marrow failure.

Front 184

Ringed Sideroblasts

Back 184

Pathology: Sideroblastic anemia

Front 185

Shistocyte, Helmet cell

Back 185

DIC, TTP/HUS, traumatic hemolysis

Front 186

Sickle Cell

Back 186

Sickle cell anemia

Front 187

Spherocyte

Back 187

(1)Hereditary spherocytosis, (2) autoimmune hemolysis.

Front 188

Teardrop cell

Back 188

Bone marrow infiltration (E.g. myelofibrosis).

Front 189

Target Cell

Back 189

HbC disease, Asplenia, Liver disease, Thalassemia.

Front 190

Heinz bodies

Back 190

Process: Oxidation of iron from ferrous to ferric form leads to denatured hemoglobin precipitation and damage to RBC membrane. Leads to formation of bite cells.

Pathology: Seen with alpha-thalassemia and G6PD deficiency.

Front 191

Howell-Jolly Bodies

Back 191

Process:
Basophilic nuclear remnants
found in RBCs.
Pathology: Seen in patients with functional hyposplenia or asplenia.

Front 192

Iron Deficiency

Back 192

--1 of 6 causes of Microcytic, hypochromic (MCV < 80) anemia.

--Decreased iron due to chronic bleeding (1st check GI bleeding), malnutrition/absorption disorders or increased demand (e.g., pregnancy) —> Decreased heme synthesis.

--May manifest as Plummer-Vinson syndrome (triad of iron deficiency anemia, esophageal web, and atrophic glossitis).

Front 193

Alpha-Thalassemia

Back 193

--1 of 6 causes of Microcytic, hypochromic (MCV < 80) anemia.
--Prevalent in Asian and African populations
--Defect: alpha globin gene mutations--> decreased alpha-globin synthesis.
DELETION of 4 genes is incompatible with life--> formation of HB Barts (gamma 4), which causes hydrops fetalis.
DELETION of 3 genes --> HGH disease (beta 4)
DELETION of 1-2 genes is not associated with significant anemia.

Front 194

Beta-Thalassemia

Back 194

Prevalent in Mediterranean populations and 1 of 6 causes of Microcytic, hypochromic (MCV < 80) anemia.
Defect: point MUTATIONS in splicing sites and promoter sequences.
BETA-THALASSEMIA MINOR (heterozygote):
(1) beta-chain is UNDERPRODUCED. (2) Usually asymptomatic. (3) Diagnosis confirmed by increased HbA2 (> 3.5%) on electrophoresis.
BETA-THALASSEMIA MAJOR (homozygote):
(1) beta-chain is ABSENT —> severe anemia requiring blood transfusion
(2° hemochromatosis). (2) Marrow expansion ("crew cut" on skull x-ray) —> skeletal deformities. (3) Chipmunk facies.
Both major and minor —> Increased HbF (alpha2gamma2)•
HbS/BETA-THALASSEMIA HETEROZYGOTE: mild to moderate sickle cell disease depending on amount of beta-globin production.

Front 195

Lead Poisoning

Back 195

--1 of 6 causes of Microcytic, hypochromic (MCV < 80) anemia.
--Lead inhibits ferrochelatase and ALA dehydratase —> heme synthesis.
Also inhibits rRNA degradation, which causes basophilic stippling from the
aggregation of ribosomes.

Front 196

Sideroblastic Anemia

Back 196

--1 of 6 causes of Microcytic, hypochromic (MCV < 80) anemia.
--DEFECT IN HEME SYNTHESIS
--Hereditary: X-linked defect in delta-aminolevulinic acid synthase gene.
Treatment: pyridoxine (B6) therapy.
Reversible etiologies: alcohol, lead.
increased iron, normal TIBC, increased ferritin.
Ringed sideroblasts (with iron-laden mitochondria).

Front 197

Lead Poisoning

Back 197

--Lead inhibits ferrochelatase and ALA dehydratase —> heme synthesis.
--Also inhibits rRNA degradation, which causes basophilic stippling from the aggregation of ribosomes.
--Lead lines on gingivae (Burton's lines) and on epiphyses of long bones on x-ray.
--Encephalopathy and Erythrocyte basophilic chipped paint stippling.
--Abdominal colic and sideroblastic Anemia.
Drops—wrist and foot drop. Dimercaprol and EDTA 1st line of treatment.

Front 198

Megaloblastic Anemia --Folate Deficiency

Back 198

--Impaired DNA synthesis maturation of nucleus delayed relative to maturation of cytoplasm. Ineffective erythropoiesis leads to pancytopenia.
--Findings: hypersegmented neutrophils, glossitis,1 folate, T homocysteine but normal methylmalonic acid.
--Etiologies: malnutrition (e.g., alcoholics), malabsorption, impaired metabolism (e.g., methotrexate, trimethoprim), t requirement (e.g., hemolytic anemia, pregnancy).

Front 199

Megaloblastic Anemia-- B12 deficiency

Back 199

--Findings: hypersegmented neutrophils, glossitis, Decreased B12, Increased homocysteine, Increased methylmalonic acid.
--Etiologies: insufficient intake (e.g., strict vegans), malabsorption (e.g., Crohn's disease), pernicious anemia, Diphyllobothrium latum (fish tapeworm).
--Neurologic symptoms: subacute combined degeneration (due to involvement of B12 in fatty acid pathways).
1. Peripheral neuropathy with sensorimotor dysfunction
2. Posterior columns (vibration/proprioception)
3. Lateral corticospinal (spasticity)
4. Dementia

Front 200

Nonmegaloblastic macrocytic anemias

Back 200

1. Liver disease
2. Alcoholism: macrocytosis and bone marrow suppression can occur in the absence of folate/B12 deficiency
3. Reticulocytosis: reticulocytes are bigger than mature RBCs —> T MCV
4. Metabolic disorder (e.g., orotic aciduria): congenital deficiencies of purine or pyrimidine synthesis
5. Drugs: 5-FU, AZT, hydroxyurea

Front 201

Porphyria Cutanea Tarda

Back 201

Defect: Uroporphyrinogen decarboxylase
Accumulated substrate: Uroporphyrin
Presenting symptoms: Blistering cutaneous photosensitivity. Most common porphyria.

Front 202

Hemophilia A

Back 202

INTRINSIC pathway coagulation disorder (not platelet defect).
--Deficiency of factor VIII
--causes an increased PTT (no change in PT).
--Macrohemorrhage in hemophilia--hemarthroses (bleeding into joints), easy bruising, PTT.

Front 203

Hemophilia B

Back 203

--Intrinsic Pathway coagulation defect (NOT platelet disorder)
--Deficiency of factor IX which causes an increased PTT.
--Macrohemorrhage in hemophilia--hemarthroses (bleeding into joints), easy bruising, PTT.

Front 204

Vitamin K deficiency

Back 204

--Causes a general coagulation disorder (not platelet disorder)
--Results in decreased synthesis of factors II, VII, IX, X, protein C, and Protein S.
--Leads to an increased PT and PTT.

Front 205

Normal Heme synthesis

Back 205

Pg. 354

Front 206

Bernard-Soulier Disease

Back 206

--Defect: Decreased GP1b (responsible for platelet-to-collagen adhesion).
--Defect in platelet plug formation--> increased bleeding time (BT)
--Labs: Decreased PC and increased BT.

Front 207

Glanzmann's Thrombasthenia

Back 207

--One of the platelet disorders.
--Defect: Decreased GpIIb/IIIa (responsible for platelet-to-platelet aggregation).
--Labs: (1) Blood smear shows no platelet clumping. (2) NO change in PC (3) Decreased BT

Front 208

Idiopathic Thrombocytopenic purpura (ITP)

Back 208

--Platelet disorder which causes decreased platelet survival.
Defect: anti-GpIIb/IIIa antibodies
--Causes a peripheral platelet destruction.
Labs: Increased Megakaryocytes.

Front 209

Thrombotic Thrombocytopenic purpura (TTP)

Back 209

Platelet disorder because of decreased platelet survival.
--Defect: ADAMTS13 (vWF metalloprotease) --> decreased degradation of vWF multimers.
--Pathogenesis: Increase in large VWF multimers --> Increased platelet aggregation and thrombosis.
Labs: (1) Schistocytes, (2) Increased LDH.
Symptoms: Pentad: (1) Neurologic sx (2) Renal sx (3) Fever (4) Thrombocytopenia (5) Microangiopathic hemolytic anemia.

Front 210

Von Willebrand's Disease

Back 210

--Mixed platelet and coagulation disorder
--Intrinsic pathway coagulation defect: Decreased vWF --> normal or Increased PTT (depends on severity; vWF acts to carry/protect factor VIII).
--Defect in platelet plug formation: Decreased vWF --> defect in platelet-to-collagen adhesion.
--Mild but most common inherited bleeding disorder autosomal dominant. Treatment DDAVP (desmopressin), which releases vWF stored in endothelium.
Labs: (1) No change in PC (2) Increased BT (3) No change in PT (4) No change or Increased PTT.

Front 211

DIC

Back 211

--Mixed platelet and coagulation disorder
--Widespread activation of clotting leads to a deficiency in clotting factors, which creates a bleeding state.
Causes: Sepsis (gram negative), Trauma, Obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion (STOP Making New Thrombi).
Labs: Schistocytes, increased fibrin split products (D-dimers), Decreased fibrinogen, Decreased factors V and VIII.
OTHERS: (1) Decreased PC (2) Increased BT (3) Increased PT (4) Increased PTT.

Front 212

Factor V Leiden

Back 212

--Most common cause of inherited hypercoagulability
--Defect: Mutant factor V that can not be degraded by protein C.

Front 213

Prothrombin gene mutation

Back 213

--Defect: Mutation in 3' untranslated region.
--Associated with venous clots.

Front 214

Antithrombin III deficiency

Back 214

--Inherited deficiency of antithrombin--> reduced increase in PTT after administration of heparin.

Front 215

Protein C or S deficiency

Back 215

--Decreased ability to inactivate factors V and VIII.
--Increased risk of thrombotic skin necrosis with
hemorrhage following administration of warfarin.

Front 216

Leukemia vs. Lymphoma

Back 216

Leukemia—lymphoid neoplasms with widespread involvement of bone marrow. Tumor cells are usually found in peripheral blood.

Lymphoma—discrete tumor masses arising from lymph nodes.
Presentations often blur definitions.

Front 217

Leukemoid reaction

Back 217

--Often confused with leukemia.
--Increased WBC count with left shift (e.g. 80% bands) and Increased leukocyte alkaline phosphatase, usually due to infection.

Front 218

Hodkin's Lymphoma

Back 218

--Presence of Reed-Stemberg cells
--Localized, single group of nodes; extranodal rare;
contiguous spread (stage is strongest predictor of prognosis)
--Constitutional ("B") signs/symptoms—low-grade
fever, night sweats, weight loss
--Mediastinal lymphadenopathy
--50% of cases associated with EBV; bimodal distribution
—young and old; more common in men except for
nodular sclerosing type
Good prognosis = increased lymphocytes, Decreased RS

Front 219

Non-Hodgkin's Lymphoma

Back 219

--May be associated with HIV and immunosuppression
--Multiple, peripheral nodes; extranodal involvement
common; noncontiguous spread
--Majority involve B cells (except those of lymphoblastic T-cell origin)
--Fewer constitutional signs/symptoms
--Peak incidence for certain subtypes at 20-40 years of age

Front 220

Burkitt's Lymphoma

Back 220

--1 of non-hodgkin's lymphoma
--Neoplasm of mature B cells
Defects: t(8;14) c-myc gene moves next to heavy-chain Ig gene (14).
--"Starry-sky" appearance (sheets of lymphocytes with interspersed macrophages).
--Associated with EBV.
--Jaw lesion in endemic form in Africa; pelvis or abdomen in sporadic form

Front 221

Diffuse Large B-cell lymphoma

Back 221

--1 of non-hodgkin's lymphoma
--Neoplasm of mature B cells
--Most common adult NHL.
May be mature T cell in origin (20%).
--Usually older adults, but 20% in children.

Front 222

Mantle Cell Lymphoma

Back 222

--A type of Non-hodgkin's lymphoma
--Neoplasm of mature B cells
--Older males
Defect: t(11,14)
Comments: Poor prognosis, CD5+

Front 223

Follicular Lymphoma

Back 223

--A type of Non-Hodgkin's lymphoma
--Neoplasms of mature B-cells
--Happens in adults
Defect: t(14;18) bcl-2 expression
--Difficult to cure; indolent course; bcl-2 inhibits apoptosis.

Front 224

Adult T-cell lymphoma

Back 224

--Caused by HTLV-1
--Neoplasms of mature T-cells
--Adults present with cutaneous lesions;
especially affects populations in Japan,
West Africa, and the Caribbean.
--Aggressive.

Front 225

Mycosis fungoides/Sezary syndrome

Back 225

--Neoplasms of T-cells
--Type of Non-Hodkin's lymphoma
--Adults present with cutaneous patches/nodules.
--Indolent CD4+.

Front 226

Multiple Myeloma

Back 226

--Monoclonal plasma cell ("fried-egg" appearance)
cancer that arises in the marrow and produces large
amounts of IgG (55%) or IgA (25%).
--Most common 1° tumor arising within bone in the elderly (> 40-50 years of age).
Associated with:
(1) increased susceptibility to infection (2) Primary amyloidosis (AL)
(3) Punched-out lytic bone lesions on x-ray (4) M spike on protein electrophoresis (5) Ig light chains in urine (Bence Jones protein)
(6) Rouleaux formation (RBCs stacked like poker
chips in blood smear)
Distinguish from Waldenstrom's macroglobulinemia
—> M spike = IgM (--> hyperviscosity symptoms); no
lytic bone lesions.

Front 227

Monoclonal Gammaopathy of undetermined significance (MGUS)

Back 227

Monoclonal plasma cell expansion without the symptoms of multiple myeloma.

Front 228

Acute Lymphoblastic leukemia/lymphoma (ALL)

Back 228

--effects Children less than 15 years
--May present with bone marrow involvement in childhood or
mediastinal mass in adolescent males.
--Bone marrow replaced by increased lymphoblasts.
--TdT+ (marker of pre-T and pre-B cells), CALLA+
Most responsive to therapy.
May spread to CNS and testes.
t(12;21) —> better prognosis.

Front 229

Small Lymphocytic lymphoma (SLL)/Chronic lymphocytic leukemia (CLL)

Back 229

--affects older adults
--Often asymptomatic; smudge cells in peripheral blood smear;
warm antibody autoimmune hemolytic anemia.
--SLL same as CLL except CLL has T peripheral blood
lymphocytosis.

Front 230

Hairy Cell Leukemia

Back 230

--Mature B-cell tumor in the elderly. Cells have filamentous,
hairlike projections.
--Stains TRAP (tartrate-resistant acid phosphatase) positive.



NOTES:
--Osteoclast bone cells stain + for TRAP.

Front 231

Acute Myelogenous Leukemia (AML)

Back 231

--affects adults
--Auer rods;
--INCREASED circulating myeloblasts on peripheral smear; adults.
--M3 responds to all-trans retinoic acid (vitamin A), inducing differentiation of myeloblasts.

Front 232

Chronic myelogenous
leukemia (CML)

Back 232

--Defined by the Philadelphia chromosome (t[9;22], bcr-abl);
myeloid stem cell proliferation; presents with T neutrophils,
metamyelocytes, basophils; splenomegaly; may accelerate and
transform to AML or ALL ("blast crisis").
--Very low leukocyte alkaline phosphatase (vs. leukemoid reaction).
--Responds to imatinib (anti-bcr-abl antibody).

Front 233

Heparin

Back 233

MECHANISM: Cofactor for the activation of antithrombin, thrombin, and Xa. Short half-life.
CLINICAL USE: Immediate anticoagulation for pulmonary embolism, stroke, acute coronary syndrome, MI, DVT. Used during pregnancy (does not cross placenta). Follow PTT.
TOXICITY: Bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions. For rapid reversal (antidote), use PROTAMINE SULFATE (positively charged molecule that binds negatively charged heparin).
NOTES
--Newer low-molecular-weight heparins (e.g., enoxaparin) act more on Xa, have better bioavailability and 2-4 times longer half-life. Can be administered subcutaneously and without laboratory monitoring. Not easily reversible.
--Heparin-induced thrombocytopenia (HIT) — heparin binds to platelet factor IV, causing antibody production that binds to and activates platelets leading to their clearance and resulting in a thrombocytopenic, hypercoagulable state.

Front 234

Lepirudin, bivalirudin

Back 234

Hirudin derivatives; directly inhibit thrombin. Used as an alternative to heparin for anticoagulating patients with HIT.

Front 235

Warfarin (Coumadin)

Back 235

MECHANISM: Interferes with normal synthesis and gamma-carboxylation of vitamin K–dependent clotting factors II, VII, IX,
and X and protein C and S.
--Metabolized by the cytochrome P-450 pathway. In laboratory assay, has effect on EXtrinsic pathway and INCREASED PT. Long half-life.
CLINICAL USE: Chronic anticoagulation. Not used in pregnant
women (because warfarin, unlike heparin, can frozen plasma.
cross the placenta).
--Follow PT/INR values.
TOXICITY: Bleeding, teratogenic, skin/tissue necrosis,
drug-drug interactions.
NOTES: For reversal of warfarin overdose, give vitamin K.
--For RAPID reversal of severe warfarin overdose, give fresh frozen plasma.

Front 236

Clopidogrel, Ticlopidine

Back 236

MECHANISM: Inhibit platelet aggregation by irreversibly blocking ADP receptors. Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa expression.
CLINICAL USE: Acute coronary syndrome; coronary stenting. incidence or recurrence of thrombotic stroke.
TOXICITY: Neutropenia (ticlopidine).

Front 237

Aspirin

Back 237

MECHANISM: Acetylates and irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) to prevent conversion of arachidonic acid to thromboxaneA2 (TxA2). INCREASED bleeding time. No effect on PT, PTT.
CLINICAL USE: Antipyretic, analgesic, anti-inflammatory, antiplatelet drug.
TOXICITY: Gastric ulceration, bleeding, hyperventilation, Reye's syndrome, tinnitus (CN VIII).

Front 238

Abciximab

Back 238

Mechanism: Monoclonal antibody that binds to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation.
Clinical use: Acute coronary syndromes, percutaneous transluminal coronary angioplasty.
Toxicity: Bleeding, thrombocytopenia.

Front 239

Methotrexate (MTX)

Back 239

ANTIMETABOLITE
MECHANISM: Folic acid analog that
inhibits dihydrofolate reductase —> decreases dTMP —> Decreased DNA and Decreased protein synthesis.
CLINICAL USE: (1) Cancers-- Leukemia, Lymphomas, choriocarcinoma, and Sarcomas. (2) Non-neoplastic: Abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis.
TOXICITY: 1. Myelosuppression, which is reversible
with LEUCOVORIN (folinic acid) "rescue."
2. Macrovesicular fatty change in liver.
3. Mucositis.
4. Teratogenic.

Front 240

5-fluorouracil (5-FU)

Back 240

ANTIMETABOLITE
MECHANISM: PYRIMIDINE ANALOG bioactivated to
5F-dUMP, which covalently complexes folic acid.
This complex INHIBITS THYMIDYLATE SYNTHASE--> decreases dTMP —> Decreases DNA and decreases protein synthesis.
CLINICAL USE: (1) Colon cancer and other solid tumors, basal cell carcinoma (topical). (2) Synergy with MTX
TOXICITY: 1. Myelosuppression, which is NOT reversible with leucovorin. Overdose: "rescue" with thymidine. 2. Photosensitivity.

Front 241

6-Mercaptopurine (6-MP)

Back 241

ANTIMETABOLITE
MECHANISM: PURINE (thiol) analog —> decreases de novo purine synthesis.
--Activated by HGPRTase.
CLINICAL USE: (1) Leukemias, lymphomas (NOT CLL or Hodgkin's)
TOXICITY: (1) Bone marrow, GI, liver. Metabolized by xanthine oxidase; thus increased toxicity with allopurinol (inhibitor of xanthine oxidase).

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6-Thioguanine (6-TG)

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ANTIMETABOLITE
MECHANISM: SAME AS 6-MP: PURINE (thiol) analog
—> Decreases de novo purine synthesis.
--Activated by HGPRTase.
CLINICAL USE: (1) Acute lymphoid leukemia
TOXICITY: (1) Bone marrow depression, liver.
(2) Can be given with allopurinol.

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Cytarabine (ara-C)

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ANTIMETABOLITE
MECHANISM: Pyrimidine antagonist —> inhibition of DNA
polymerase.
CLINICAL USE: AML, ALL, high-grade non-Hodgkin's lymphoma
TOXICITY: (1) Leukopenia, thrombocytopenia, and megaloblastic anemia.

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Dactinomycin

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ANTITUMOR ANTIBIOTICS
MECHANISM: Intercalates in DNA.
CLINICAL USE: Wilms' tumor, Ewing's sarcoma, rhabdomyosarcoma.
Used for childhood tumors (children ACT out).
TOXICITY: (1) Myelosuppression

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Doxorubicin (Adriamycin), daunorubicin

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ANTITUMOR ANTIBIOTICS
MECHANISM: Generate free radicals. Noncovalently intercalate in DNA --> breaks in DNA --> Decreases replication.
CLINICAL USE: (1) Hodgkin's lymphomas; also for myelomas, sarcomas, and solid tumors (breast, ovary, lung).
TOXICITY: (1) Cardiotoxicity, myelosuppression, and alopecia. Toxic to tissues with extravasation.

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Bleomycin

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ANTITUMOR ANTIBIOTICS
MECHANISM: Induces free radical formation, which causes
breaks in DNA strands.
CLINICAL USE: (1) Testicular cancer (2) Hodgkin's lympoma
Toxicity: Pulmonary fibrosis, skin changes. Minimal myelosuppression.

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Etoposide (VP-16), teniposide

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ANTITUMOR ANTIBIOTICS
MECHANISM: Inhibits topoisomerase II --> Increased DNA degradation.
CLINICAL USE: (1) Small cell carcinoma of the lung and prostate, testicular carcinoma
TOXICITY: (1) Myelosuppression, GI irritation and alopecia.

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Cyclophosphamide, ifosfamide

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ALKYLATING AGENTS
MECHAMISM: Covalently X-link
(interstrand) DNA at guanine N-7. Require bioactivation by liver.
CLINICAL USE: Non-Hodgkin's lymphoma, breast and
ovarian carcinomas.
(2) Also immunosuppressants.
TOXICITY: Myelosuppression;
hemorrhagic cystitis, partially prevented with mesna (thiol
group of mesna binds toxic metabolite).

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Nitrosoureas (carmustine, lomustine, semustine, streptozocin)

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ALKYLATING AGENTS
MECHANISM: Require bioactivation. Cross blood-brain barrier
CNS.
CLINICAL USE: Brain tumors (including glioblastoma multiforme).
TOXICITY: CNS toxicity (dizziness, ataxia).

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Busulfan

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ALKYLATING AGENTS
MECHANISM: Alkylates DNA.
CLINICAL USE: CML. Also used to ablate patient's bone marrow
before bone marrow transplantation.
TOXICITY: Pulmonary fibrosis,
hyperpigmentation.

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Vincristine, vinblastine

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MICROTUBULE INHIBITORS
MECHANISM: Alkaloids that bind to tubulin in M-phase and
block polymerization of microtubules so that
mitotic spindle cannot form. Microtubules are
the vines of your cells.
CLINICAL USE: Hodgkin's lymphoma, Wilms' tumor,
choriocarcinoma.
TOXICITY:
Vincristine—neurotoxicity (areflexia, peripheral
neuritis), paralytic ileus.
--VinBLASTine BLASTs Bone marrow (suppression).

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Paclitaxel, other taxols

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MICROTUBULE INHIBITORS
MECHANISM: Hyperstabilize polymerized microtubules in M-phase so that mitotic spindle cannot break down (anaphase cannot occur). It is TAXing to stay
polymerized.
CLINICAL USE: Ovarian and breast carcinomas.
TOXICITY: Myelosuppression and hypersensitivity.

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Cisplatin, Carboplatin

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MECHANISM: Cross-link DNA.
CLINICAL USE: Testicular, bladder, ovary, and lung carcinomas.
TOXICITY: Nephrotoxicity and acoustic nerve damage.

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Hydroxyurea

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MECHANISM: Inhibits Ribonucleotide Reductase —> Decrease DNA Synthesis (S-phase specific).
CLINICAL USE: Melanoma, CML, sickle cell disease (increased HbF).
TOXICITY: Bone marrow suppression, GI upset.

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Prednisone

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MECHANISM: May trigger apoptosis. May even work on nondividing cells.
CLINICAL USE: Most commonly used glucocorticoid in cancer chemotherapy. Used in CLL, Hodgkin's lymphomas (part of the MOPP regimen). Also an immunosuppressant used in auto immune diseases.
TOXICITY: Cushing-like symptoms; immunosuppression, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis.

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Tamoxifen, raloxifene

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MECHANISM SERMs —receptor antagonists in breast and agonists in bone. Block the binding of estrogen to estrogen receptor–positive cells.
CLINICAL USE: Breast cancer. Also useful to prevent osteoporosis.
TOXICITY: Tamoxifen—may T the risk of endometrial carcinoma via partial agonist effects; "hot flashes." Raloxifene —no increase in endometrial carcinoma because it is an endometrial antagonist.

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Trastuzumab (Herceptin)

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MECHANISM: Monoclonal antibody against HER-2 (erb-B2). Helps kill breast cancer cells that overexpress HER-2, possibly through antibody-dependent cytotoxicity.
CLINICAL USE: Metastatic breast cancer.
TOXICITY: Cardiotoxicity.

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Imatinib (Gleevec)

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MECHANISM: Philadelphia chromosome bcr-abl tyrosine kinase inhibitor.
CLINICAL USE: CML, GI stromal tumors.
TOXICITY: Fluid retention.

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Rituximab

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MECHANISM: Monoclonal antibody against CD20, which is found on most B-cell neoplasms.
CLINICAL USE: Non-Hodgkin's lymphoma, rheumatoid arthritis (with methotrexate).