EOB Flashcards
1
Q
Sensitivity
A
TP/(TP + FN)
Probability test detects disease when disease is present
2
Q
Specificity
A
TN/(TN+FP)
Probability test indicates no disease when disease isnt present
3
Q
Positive predictive value
A
TP/(TP+FP)
4
Q
Negative predictive value
A
TN/(TN+FN)
5
Q
Conceptus
A
Product of fertilization
6
Q
Primordium
A
Organ or tissue in early stages
7
Q
Embryonic Period
A
Weeks 3-8
8
Q
Fetal period
A
Weeks 8-38
9
Q
Trimesters
A
Month 1-3, 4-6, 7-9
10
Q
Blastocyst parts (3)
A
Inner cell mass (Embryoblast)
Outer cell mass (trophoblast)
Blastocyst cavity
11
Q
Blastocyst arrival in uterus (week)
A
Week 1
12
Q
Implantation
A
Fusion of Trophoblast and endometrial epithelium
13
Q
Cytotrophoblast
A
Unfused trophoblast cells
14
Q
Syncytiotrophoblast
A
Divided trophoblast cells that are fused into endometrial epithelium
15
Q
hCG
A
Human chorionic gonadotropin
Secreted by Syncytiotophoblast –> prevents menstruation
16
Q
Gastrulation (in general)
A
Week 3
Bilaminar germ disk –> trilaminar germ disk
Endoderm
Mesoderm
Ectoderm
17
Q
Formation of endoderm
A
Epiblast cells migrate through primitive streak to replace hypoblast –> form endoderm
18
Q
Mesoderm formation
A
Epiblast cells migration through primitive streak lie between endoderm and epiblast –> mesoderm
19
Q
Ectoderm formation
A
Non migrating epiblast cells –> ectoderm
20
Q
Ectoderm develops into..
A
EpidermisCNS
21
Q
Endoderm develops into..
A
Inner lining of digestive and respiratory tracts
22
Q
Mesoderm develops into..
A
Muscles, bones, blood, connective tissues, fat
23
Q
Sacrococcygeal teratoma
A
Occurs when primitive streak cells persist
Tumors have a lot of tissues in them, teeth/hair
24
Q
Caudal regression
A
Due to failure of mesoderm formation
Cranial structures normal, inferior structures underdeveloped
25
Locations without mesoderm after gastrulation
Cloacal membrane
Buccopharyngeal membrane
Tightly bound ecto and endoderm
Will form oral and uro-genital-digestive openings
26
3 mesoderm tissues
Paraxial mesoderm
Intermediate mesoderm
Lateral plate mesoderm
27
Formation of intraembryonic coelom
Lateral plate mesoderm splits into somatic and splanchnic mesoderm
Space in between is intraembryonoic coelom
28
Somatic mesoderm development -->
Body wall, conscious sensation and movement
29
Splanchnic mesoderm development -->
Visceral, unconscious sensation and movement
30
Intraembryonic coelom development -->
Body cavities
31
Molar pregnancy
Organism only develops placenta, no embryo
| Villi swell and must be removed
32
Neurulation
```
Week 4 (end of week 3)
Notocord induces ectoderm to thicken = neuroectoderm
```
Neuroectoderm folds, creates neural groove
Neuroectoderm fuses --> neural tube formed (filled with amniotic fluid)
33
Surface ectoderm after neurulation becomes...
Epidermis
34
Direction of neural tube closure
First in middle, then cranially and caudally
35
Closing of neural tube (week)
Near week 4 end
36
Neural crest
Forms when ectoderm cells break off from neural tube and neuroectodermLateral to neural tube
37
Neural crest develops..
```
Neural cells that are outside of CNS
Schwann cells
dorsal root ganglion
Cranial nerve ganglion
Postganglionic neurons
```
38
Paraxial mesoderm condensation results in
Somitomeres --> Somites
39
Somites develop into..
Bone (migrates aroung notochord), muscle, dermis
40
Somite divides into 2 parts
Sclerotome (bone)Dermomyotome (muscle and dermis)
41
B cell development (total)
Stem cell --> Pro B --> Pre B --> Immature B --> Mature B
42
Pro B cell development
D-J rearrangements in H chain
43
Pre B cell development and Ig expression
V-D-J rearrangement in H chainCytoplasmic mu and pre B cell receptors
44
Immature B cell development and Ig expression
VJ rearrangement = Single functional light chain IgM expressed on surfaceas receptor (can't be activated by antigen)
45
Mature B cell
IgM and IgD expressionCell exits bone marrow
46
Bruton's X linked Agammaglobulinemia
Defect in btk genebtk gene product = pro B cell --> further developmentDefect = lack of humoral immunity (no B cells)No tonsils of papable lymph nodes
47
2 T cell types
Alpha-beta
| Gamma-Delta
48
T cell marker on all T cells
CD3
49
T cell markers on alpha beta
CD4 or CD8
50
Activation of T cell (3 steps)
```
Adhesion
Signal 1 (Antigen recognition)
Signal 2 (co-stimulation, B7-CD28)
```
51
Cell adhesion
Adhesion molecules help connect Tcell and APC
LFA-1/CAM-1
Transient connection
52
Antigen recognition and adhesion
TCR recognizes MHC/peptide --> Increased affinity of LFA-1
53
Leukocyte adhesion deficiency
Affects beta2 integrin subunit of LFA-1
54
Antigen recognition
TCR binding induces CD3 signal cascade
55
Costimulatory Signal
CD28-B7 (Most studied)
B7 on APC activated by microbes or innate immune response
Connect with CD28 on Tcell
56
B-cell activation by T cell (general overview)
B cell binds antigen --> Peptide derived and presented by MHC --> T helper cell recognizes
57
Helper T cell action after connected to B cell
CD40Ligand and cytokines expressed (bind to resective receptors) --> B cell activation and proliferation
58
Hapten
```
Small non immunogenic molecule
Needs carrier (eg BSA) Carrier-hapten complex is immunogenic and Ig will react to hapten alone
```
ONLY AFTER COMPLEX IMMUNIZATION
59
IL-2
Made by activated T-cellsBinds (autocrine) to t-cells (IL-2R) and induces clonal expansion and differentiation
60
3 CD4 subsets
Th1, Th2, Th17
61
Th1 cytokine
IFN-gamma
62
IFN-gamma
Activates macrophages--> increased MHC expression, cytokine secretion, reactive O-, NO, lysosomal enzymes
63
IL-12 and Th1
IL12 secreted by innate immunity --> promotes Th1 responses
64
Th2 cytokines
IL-4 --> IgE responseIL-5 --> Eosinophil activationIL-10 --> Suppress Th1IL-13 --> Like IL-4, hypersensitivity
65
IL-4
IgE response
66
IL-5
Eosinophil activation
67
IL-10
Suppresses Th1
68
Th17 cytokines
IL-17AIL17-FIL-22
69
IL-17
Inflammatory diseasesNeutrophil action
70
CD8 activation (overview)
AdhesionAg recognitionCo-stimulationIL-2 (made by CD4 or CTL)
71
CTL mechanism of action
Initiates apoptosis pathway of cellReleases granules (perforins/granzymes) = apoptotic pathway
72
NK cells
Natural killer, kill cells without MHC-1Inhibitory receptor binds to MHC-1/peptide --> no destruction
73
ADCC
Antibody dependent cellular cytotoxicityNK's bind to cells coated in IgG --> Kill cell
74
3 groups of genes involved in birth defects
Growth factor receptorsTranscription FactorsExtracellular matrix proteins
75
Anencephaly
Incomplete development of cranial neural tube --> exposed brain, undifferentiated
76
Myeloschisis
Incomplete development of the caudal neural tubeLumbar spinal cord that is undifferentiated and exposed
77
Spina bifida occulta
AsymptomaticUnfused vertebral arch but not huge opening
78
Meningocele
Only meninges protrude through defective non fused vertebral arch
79
Meningomyelocele
Neural tube breaks from ectoderm, herniates through defect
80
Phenytoin
AnticonvulsantTeratogen --> Fetal hydantoin syndromeHeart malformations, facial clefts, limb defectsMetabolized by phase 1 enzyme of epoxide hydrolase
81
Mercaptopurine
Metabolized by thiopurine methyltransferase (TPMT)
82
Pili
Protein projections on surface of bacteria (made of pilin)Major role in adherence, attach to receptors on host cellAntigenic, anti-phagocytic, variable
83
Spores
Small metabolically quiescent forms of bacteria, produced as survival mechanismCan withstand extreme environments
84
Exotoxin
Proteins that bind to host cell (B domain) and damage/kill host (A domain)
85
Diptheria toxin
Stops protein synthesisA domain ADP-ribosylates elongation factor 2 --> no protein synthesis
86
Cholera toxin
A domain ADP-ribosylates GTP binding protein, constant cAMP --> diarrhea
87
Tetanus and Botulinum toxins
Cleave vesicle fusion proteinsBlock neurotransmitter release
88
Bacterial endotoxins
1. Integral to bacteria structure2. Composed of lipopolysaccharide3. Gram negative ONLY
89
Steps for microorganism infection
1. Entry2. Spread3. Multiplication4. Transmission5. Pathology
90
TNF-alpha
Endogenous pyrogen (fever)Made by macrophageIncreases vascular permeability --> complement and increased fluid drainage to lymph nodes
91
Type 1 Interferon response
Induce resistance to viral replication (RNA and Protein synthesis level)Increase NK cell receptor ligandsActivate NK cellsInterferons released when cell is killed by virus, induces response in neighboring cells
92
HIV and chemokine relationship
HIV binds to chemokine receptors (CXCR4, CCR5)
93
Th1 pattern of cytokines =
Enhanced phagocytosis
94
Th2 pattern of cytokines
M2 or alternative pattern, wound healing
95
M2 macrophage
Wound repair, fibrosis
96
Superantigen
Activates T cellsBinds to MHC class 2 outside of peptide binding groove and Vbeta of TCR
97
High endothelial venules
Path of naive T cell trafficking to specific peripheral lymphoid tissueHoming based on specific homing receptors interacting with HEV receptors
98
Difference between fungi and human cells
Plasma membraneCell wall
99
Fungi cell wall
90% polysaccharides10% proteinsMannansGlucansChitin
100
Mannan
Mannose polymersAttached to surface proteins
101
Glucans
Glucose polymersStrength
102
Chitin
N-acetylglucosamine polymerStrength
103
Moulds
Form hyphae-Tube like structuresHyphae fusion = mycelium (colony)
104
Yeast
UnicellularBudding reproduction
105
Aflatoxin
Food contaminant
106
Fungi virulence/pathogenesis(steps)
AdherenceInvasionTissue damageHost evasion
107
Fungi adherence
Fungal surface proteins/carbohydrates bind human cell receptors
108
Invasion
Hyphal pathogens
109
Tissue damage
Degradative enzymes
110
Host evasion
Avoid recognitionEscape phagocytic killing
111
Superficial fungi
Environmentally acquired
112
Opportunistic fungi
Emerge in diseased hosts only
113
Pneumocystis jirovecci
Acquired by inhalation, but held in check by immune systemPneumocystis pneumonia in diseased patients
114
Systemic fungi
Infects healthy host Environmental transmission
115
Histoplasmosis
Found in caves, bat is the host
116
Antifungal innate immunity
PAMP's recognized by PRR's
117
Common fungal PAMP and human PRR
PAMP: Beta GlucanPRR: Dectin-1
118
Azoles
Block ergosterol synthesisFluconazoleVoriconazolePosaconazole
119
Allylamines
Block ergosterol synthesisTerbinafine (Lamisil)
120
Polyenes
Bind ergosterol (form pore)Higher toxicityAmphotericin BNystatin (topical)
121
Echinocandins
Block glucan synthesisCaspofunginAnidulofunginMicafungin
122
Pyrimidine Analogs
Block DNA/RNA synthesisFlucytosineRapid resistance, works in combo therapy
123
Fertilization (sperm)
Burrow through corona radiata and zona pellucidaEnzymes released from acrosome
124
Fertilization (oocyte)
Release cortical granules (confirmation change to prevent polyspermy)Finish meiosis IIBegin metabolism
125
Schistosoma mansoni
Flatworm infestation
126
Tapeworm (alternate name)
Cestode
127
Fluke (alternate name)
Trematode
128
Entamoeba Histolytica
Amebic parasite found in dirty water/foodOr Butt stuff
129
Ciliated or flagellate protozoan parasites more common?
Flagellate
130
Trichomonas vaginalis
Sexually transmitted flagellate protozoan
131
T cell development stages
Double negative --> Double positive --> +/-+/- in medulla of thymus
132
Transition from +/+
Recognition of MHC Class II = CDR-4+Recognition of MHC class I = CD-8+No recognition/too strong recognition = apoptosis
133
Cytokine signal transduction
JAK/STAT pathway
134
IL-2 and T cell affinity
Only activated T cells express Alpha unit of IL-2R and will respond to IL-2
135
Th2 defends host against...
Helminthic parasites
136
Th1 defends hosts against...
Foreign intracellular microbes
137
Th17 defends host against...
Extracellular bacteria/fungi
138
Pyrogens
TNF-alphaIL-1IL-6
139
Path of virus after entry into body
Taken up by APC (dendritic cell) --> Travel to lymphoid tissue
140
M1 phagocytosis
Microbe binds to phagocyte receptor --> Phagocyte membrane envelopes microbe --> Fuse with lysosome --> microbe killedTh1 cytokines
141
Positive sense RNA viruses
Virion RNA = mRNAImmediate translation
142
Negative sense RNA viruses
RNA is complementary to mRNA Need RNA dependent RNA polymerase packaged with it to transcribe then translate
143
Double stranded RNA viruses
RNA polymerase needed to make mRNA
144
Problem of monocistronic RNAs in human?
Humans only operate with single mRNA'sViruses translate singe mRNA and cleave product to make multiple proteins
145
Forces driving viral diversity
MutationSelectionReassortmentGenetic drift/founder effect
146
Immune escape
Gradual accumulation of mutations (genetic drift)
147
Productive infection
Cell has appropriate receptors and machinery for viral replication, production, and release
148
Null
Cell does not have appropriate receptors
149
Abortive
No virion formation after entryInsufficient DNA/RNA production or non infectious virions produced
150
Restrictive
Cell is transiently permissive, only few viruses producedNo more production but virus genome still present
151
Gram+ bacteria
Thick peptidoglycanTeichoic acid
152
Gram- bacteria
Outer membrane with LPS
153
LPS
LipopolysaccharideLipid A portion responsible for endotoxin activity
154
FluconazoleVoriconazolePosaconazole
AzoleBlock ergosterol synthesis
155
Terbinafine (Lamisil)
AllylamineBlocks ergosterol synthesis
156
Amphotericin B
PolyeneBinds ergosterol, forms pore
157
Nystatin
PolyeneBinds ergosterol, forms pore
158
CaspofunginAnidulofunginMicafungin
EchinocandinsBlock glucan synthase
159
Flucytosine
Pyrimadine analogBlock DNA/RNA synthesis
160
Giardia lamblia
Most common intestinal protozoan in USDiarrheaWater borne cysts
161
Chagas disease
Parasite that causes heart disease
162
Ascariasis
Infestation of ascaris lumbridoidesNematodeFecal-oral transmission of eggs in contaminated food
163
Percent of babies born with birth defect
3%120,000/year in US
164
Most common birth defect
Congenital heart defect1% of all births40,000 new cases per year
165
Cleft lip prevalence/incidence
P: 1/1000I: 7000 a year
166
Down's syndrome prevalence/incidence
P: 1/1000I: 6000 a year
167
3 major components of embryonic development
Pattern formationAxis specificationOrganogenesis
168
FGFR3 diseases
HypochondroplasiaThanatophoric dysplasiaAchondroplasia
169
FGFR2 disease
Apert syndromeDigit fusion, face hypoplasia
170
Hirschsprung disease
P: 1/5000Lack of nerve cells in enteric tractRET oncogene mutation
171
Hox genes
Anterior/posterior axis
172
Situs inversus caused by...
DyneinPolycystin-2
173
Type I hypersensitivity
Immediate - IgEAntigen exposure --> Th2 activation --> IL-4 and IgE --> IgE + mast cells --> Release of mediators (After repeat exposure)
174
Histamine
Immediately released
175
Late phase (activated mast cell)
Release of prostaglandins and leukotrienesAnd Cytokines (TNF-a, IL-4, IL-5)
176
Type II hypersensitivity
Tissue/organ specificAntibody/antigen complex --> Complement activation --> inflammation and tissue injury (neutrophils, ROS)
177
Drug induced hemolytic anemia
Drug (hapten) binds to RBC --> induces pathway for hapten Ab generation --> Ab bind to RBC --> lysis or phagocytosis or complement activated phagocytosisOccurs when hapten binds to own cell
178
Grave's disease
HyperthyroidismAntibodies bind to TSH receptor --> constitutive release of thyroid hormonesCan pass from mother to to child
179
Rheumatic fever
Group A Streptococcal pyogenesStreptococcal cell wall stimulates Ab response --> antibodies cross react with heart tissue antigens
180
Type III hypersensitivity
Soluble immune complex - systemicComplex becomes larger --> complement mediated recruitment of activation of inflammatory cells
181
Serum sickness - Type III hypersensitivity
Patients given bolus of foreign antibody (against specific disease eg. tetanus) --> antibodies made against antigen --> antigen:antibody complexes form --> type III hypersensitivity
182
Arthus reaction
Inject antigen --> antigen:antibody complexes form --> complement activation --> inflammation (neutrophil recruitment)
183
Systemic Lupus Erythematosus
Systemic auto immune disease (Type III hypersensitivity)Making antibodies against nuclear antigens --> Ag-Ab complexes --> Complement levels decrease --> kidneys affected
184
Type IV Hypersensitivity (DTH)
Antigen introduced --> Processed by APC --> Th1 recognition --> macrophage activation CD4 or CD8
185
Contact hypersensitivity
DTH
186
Active immunization
Immunized individual acquires immunity to specific antigen
187
Passive immunization
Preformed antibodies providing temporary protection
188
T independent antigen
Repeating epitopes that cross link Ig receptors on B cellsActivates B cell without use of T cellNo memory, no H chain switching, no affinity maturation
189
Conjugate vaccine
Add T-I antigen to carrier protein --> internalized and presented by B cell --> t cell activation --> B cell activation --> Ab secreted
190
Conjugate vaccine examples
Hib, PCV14, Meningococcal
191
4 methods of resistance
Enzymatic degradationAltered target Decreased uptakeIncreased efflux
192
Concentrated dependent killing
Higher concentration = more rapid, complete cell kill. Decreased resistance
193
Time dependent killing
Saturation of killing occurs at low multiples of MIC
194
Cell wall inhibitors
Beta-lactamsGlycopeptides
195
Cell membrane inhibitors
DaptomycinPolymyxins
196
Nucleic acid inhibitors
Fluoroquinolones
197
Protein Synthesis inhibitors
50S ribosome30S ribosome
198
Metabolic inhibitors
SulfonamidesTrimethoprin
199
Difference between Penicillins and cephalosporins
Cephalosporins have 6 membered ring, penicillins have 5 Cephalosporins have 2 R groups
200
Penicillin binding protein
Enzymes that catalyze last step of cell wall synthesis
201
PBP and Beta lactam
B-Lactam is structurally analagous to D-Ala-D-Ala --> react with PBP and create intermediate so cell wall is not fully synthesized
202
Beta lactamase
Breaks bond in Beta lactam ringMolecule disabled
203
Beta lactamase inhibitor
Binds to beta lactamase so it can't functionExtends life of beta-lactam drug
204
Natural penicillin
Narrow spectrumStreptococci, treponemaPenicillin G, VK
205
Anti-staphylococcal
Narrow spectrumStaph-MSSA onlyHas beta-lactamses
206
Amino penicillins
Broad spectrum - Gram+ (not MRSA), some gram(-)Augmentin
207
Ureido penicillin
Piperacillin+tazobactamVery broad spectrum (enhanced gram- incl. Pseudomonas)
208
1st generation Cephalosporin
Narrow (Gram +)Staphylococci, streptococciCefazolinCephalexin
209
2nd generation Cephalosporins
Broader than 1st gen, includes anaerobes
210
3rd generation cephalosporin
Broad, enhanced gram-PseudomonasCeftriaxone - does not cover pseudomonas
211
4th generation cephalosporins
Very broad spectrumEnhanced gram(-), includes PseudomonasCefepime
212
5th generation cephalosporins
CeftarolineBroad spectrum, MRSA coverageBinds to altered target site on MRSA
213
Monobactams
Inhibits gram negatives onlyPoor PBP binding of gram+Penicillin allergies
214
Carbapenems
Stable to most Beta-lactamasesVery broad, used rarely to avoid resistance
215
Beta lactam adverse effects: Common
GI: Nausea/loose stoolsTaking drug for a while/high doses
216
Beta lactam uncommon/rare adverse effects
Uncommon: Hypersensitivity - Non IgE mediated rashRare: Hypersensitivity - anaphylaxis
217
Vancomycin
Large, tricyclic glycopeptideCell wall inhibitor - binds to D-ala-D-ala so it cant bind to PBPStep before Beta lactam
218
Vancomycin spectrum and target
Only active vs gram (+)Drug of choice for MRSAClinical resistance is low
219
Vancomycin ADME
A: Not absorbed orallyD: Does not cross BBBM: NegligibleE: KidneyMonitor drug concentration, keep 10-20ug/mL
220
Vancomycin toxicity
1. Nephrotoxicity2. Red-man syndrome- Flushing, erythema, angioedema-Not IgE3. Ototoxicity
221
Daptomycin
Cell membrane inhibitorGram(+) via Ca dependent interaction w/membraneMRSA - Alternative to Vancomycin
222
Polymyxins
Binds with negative LPS --> permeability changes, leakage, cell deathGram(-)Last resort for MDR-organisms
223
Polymyxins Adverse Effects
NephrotoxicityNeurotoxicityTopical combination products are safe
224
Most common Fluoroquinolones
Ciprofloxacin (Cipro)Levofloxacin (Levaquin)Moxifloxacin (Avelox)Gemifloxacin (Factive)
225
FluoroquinoloneMoA, Spectrum, Resistance, PK/PD
MoA: Inhibit DNA gyrase and topoisomerase- blocks DNA replication, inhibit nucleic acid synthesisBroad spectrum: Gram +/-, atypicals, TBOral absorption
226
Fluoroquinolone adverse effects
GI: Loose stoolsCNS: HA, lightheadedness, nervousnessSkin: PhotosensitivityBoxed warning: Tendonitis/rupture, peripheral neuropathy, dysclycemiaNot good for children or prego chicks (unless benefit > risk)
227
50S ribosomal unit protein synth inhibitor
MacrolidesOxazolidinonesLincosamidesChloramphenicol
228
30S ribosomal unit protein synth inhibitor
AminoglycosidesTetracyclines: Doxycycline
229
Aminoglycoside/Tetracycline MoA
Bind to 30S ribosomePrevent binding of incoming charged tRNA
230
50S subunit drug MoA
Bind to 50S subunit and block peptide bond formation
231
Macrolides
Azithromycin (Zithromax)Inhibit protein synthesisBacteriostatic, time dependent killing, anti-inflammatoryLow level resistance (efflux pump)High level resistance (target site modification)Broad spectrum: Gram+, Neisseria, TreponemaChoice for atypicals
232
Macrolides clinical use
STI: Chlamydia, GonorrheaRTI: Pharyngitis, otitis, CAP
233
Macrolide adverse effects
GI (higher than most classes)May increase QTc interval
234
Erythromycin Drug interactions
P450 inhibitor
235
Oxazolidinones (Linezolid)
Inhibits protein synthesis at early stageNarrow spectrum: Gram+Alt for MRSA
236
Linezolid Adverse effects
GISkin rashesSerotonin syndrome: SSRI's use blocked because MAO inhibition by drug
237
Lincosamide: Clindamycin
50S inhibitorBroad spectrum: Gram(+), anaerobes, toxoplasmaAdverse effects: Diarrhea, C.difficile colitisOlder drug
238
Chloramphenicol
50S binding --> block peptide bond formationBroad spectrum: Gram(+), (-) anaerobes
239
Chloramphenicol adverse effects
Reversible bone marrow suppressionAplastic anemiaGray baby syndrome
240
Aminoglycosides
Irreversible binding to 30S --> enzyme modificationSpectrum: Gram (-), synergistic activity with gram(+) cell wall agentsHigh dose, extended intervalRequire serum level monitoring
241
Aminoglycoside toxicity
Nephrotoxicity (5-25%)-5-7 daysOtotoxicity (1-5%)Neuromuscular blockade
242
Tetracycline
Doxycycline, tigecycline (MDR)Bind to 30S, block initiation complexBroad spectrum: Gram(+/-)
243
Tetracycline adverse effects
GIPhotosensitivityBad in children
244
Tetracycline drug interaction
Cations impair absorptionMay decrease effect of oral contraceptives
245
Sulfonamide
Folate inhibitorsUsed in combinationBlock purine production and nucleic acid synthesisBroad spectrum: Gram(+/-)
246
Nitrofurantoin
Inhibits several enzyme systems: Acetyl CoA --> inhibit metabolismGram(-) - E.coliBladder infectionsGI, rash, pulmonary
247
Guanosine analogs
AcyclovirValacyclovirFamciclovirChain termination (inhibits DNA chain elongation)Genital herpesValacyclovir = acyclovir prodrugFamciclovir: HIgher doses, less frequent
248
CMV antivirals
Ganciclovir: similar to acyclovirValganciclovir (Ganciclovir prodrug)
249
CMV antivirals adverse effects/drug interactions
GI, insomnia/confusion, rashBone marrow toxicity, mutagenic/embryotoxicityInteract with myelosuppressive agents, seizure potential
250
Foscarnet MoA, spectrum/use
Inhibits DNA polymerase - pyrophosphate analogCMV, Acyclovir resistant HSV
251
Foscarnet Adverse effects/interactions
NephrotoxicityBone marrow toxicityElectrolyte imbalance
252
Cidofovir
Cytosine nucleotide analogInhibits DNA polymeraseCMV, acyclovir resistant HSV
253
Cidofovir adverse effects
NephrotoxicityBone marrow toxicityCarcinogenic, mutagenic
254
Adamantanes
Influenza antiviralInhibit viral uncoatingInfluenza A only
255
Adamantanes ADR
CNS: dizzy, nervous, insomniaGITeratogenic, embryotoxic
256
Sialic acid analogs
Inhibit viral neuraminidase: clumping of virionsInfluenza A/B
257
Sialic acid analog ADR
Zanamivir: CoughOseltamivir: GIPeramivir: Skin
258
Fiber types
CollagenReticularElastic
259
Collagen properties
Tensile strength
260
Reticular fiber properties
Tensile strength
261
Elastic fiber properties
Resiliency
262
Proteoglycan properties
Rigidity, porosity
263
Mast cells
Granules contain bioactive substances: Histamine, leukotrienes, proteolycansSlow release of granule regulates innate immune responses
264
Histamine
Causes bronchoconstriction by inducing contraction of smooth muscleTriggers vasodilation, lowers BP
265
Epinephrine
Binds to adernergic receptorsSmooth muscle relaxation in airways, smooth muscle contraction
266
Exposure
Contact with a microbe
267
Infection
Acquisition by a hostSynonymous with disease
268
Commensalism
Microbe that co-exists with host
269
Mutualism
Host and microbe benefit
270
Colonization
Microbe found in non sterile site without causing disease
271
Latency
Microbe harbored without causing damage
272
Disease
Clinical evidence that microbe is causing damage to host tissues
273
Pathogen
Microbe that causes disease or damage to host
274
Sepsis
Systemic response to an infectious agent - bacterial, viral fungal
275
Sepsis clinical responses
Change in temperatureTachycardiaTachypneaAlteration in white blood cell count
276
Sepsis mediators
ComplementCoagulation cascadePro-inflammatory mediatorsAnti- inflammatory mediators
277
Sepsis benefits? White cells, Tachycardia, Tachypnea, fever
White cells combat infectionTachycardia increase COTachypnea increases ventilationFever inhibits microbial growth
278
Septic shock
Sepsis and evidence of insufficient organ perfusion and oxygen delivery
279
Treating sepsis
Lactate measurementBlood culturesBroad spectrum antibioticsFluid resuscitation
280
Sepsis epidemiology
~750,000 cases in N. America~40,000 children30-35% mortality in adults, 10% in children19,000,000 cases worldwide
281
Acute inflammation causes
Foreign intruderTissue necrosisTraumaImmune reactions
282
Vascular reactions
VasodilationIncreased permeabilityVascular stasis
283
Cellular reactions
ExtravasationChemotaxisActivationPhagocytosis
284
Vasodilation
Arteriolar dilation --> hyperemia --> Rubor, calorRedness/heat
285
Increased permeability
Endothelial gapsNeutrophil entry is easierEdema
286
Vascular stasis
Slowed blood flow, more time for leukocytes to contact endothelial cells
287
Extravasation
Roll, bind, squeeze through epitheliumRoll: SelectinsAdhesion: IntegrinsTransmigration: PCAM-1
288
Chemotaxis
Respond via receptors, locomotion based on chemical gradient
289
Activation
Increase defensive functions - more enzymes
290
Phagocytosis
OpsinizationEngulfmentKilling/degradation
291
Chronic inflammation
Prolonged durationMacrophages, lymphocytes, plasma cell
292
Chronic inflammation causes
Acute inflammationPersistent infectionsProlonged irritationAutoimmunity
293
Lymphocyte-Macrophage interaction
Activate macrophage --> TNF-a/IL-1 activates lymphocyte --> Activated lymphocyte IFN-gamma --> Macrophage activated
294
Granulomatous inflammation
Special form of chronic inflammationEpithelioid macrophagesMyobacterium TB, histoplasmosa capsulatum, non infectious materials resistant to degradation
295
Leukocytosis
Increase in leukocytesAccelerated release from marrowImmediate release of storage pools (Vasculature, spleen)
296
C-Reactive Protein
Liver response to inflammation'Binds to damaged tissue and microbes, activates complement/pro-inflammatory cytokines
297
Hematopoietic cells
Erythroid precursorsMegakaryocytesLymphocytesPlasma cellsMonocytes/macrophages
298
Stromal cells
Fibroblasts/reticulinAdiposeOsteoclasts/blastsEndothelial cells
299
Hematopoietic stem cell
MultipotentSelf renewalDifferentiation
300
Simple squamos cells
Wider than tallFried egg appearance Allows materials to pass through
301
Simple squamos examples
Endothelium - lining of blood/lymph vessels, heart cavitiesMesothelium - lining of serous cavities: Pericardium, peritoneum
302
Simple cuboidal
Width = depth = heightPrevalent in secretory/absorption
303
Simple cuboidal examlpes
Thyroid folliclesSmaller ducts/glandsGerminal epithelium of ovaryKidney ducts
304
Simple columnar
Taller than wide, oval nucleus @ baseProtection and secretion
305
Plain tall columnar
Mucosa of stomachSI, LIGall bladderBigger ducts of glands
306
Ciliated Columnar
Cells with ciliaUterus and oviducts
307
Pseudostratified columnar
All cells touch BM but do not reach surface
308
Pseudostratified columnar w/motile cilia
Respiratory system: Nasal, larync, trachea, oviducts
309
Pseudostratified columnar w/motile cilia and goblet cells
Respiratory system
310
Goblet cells
Mucous secreting cells
311
Pseudostratified columnar w/non motile cilia
Epididymis
312
Pseudostratified columnar non ciliated
Ductus deferens
313
Stratified squamos example
Skin, lining of cavities opening to skin: Mouth, vestibule of nose, anusMore than 1 layer
314
Keratinzed stratified squamos
Protective layer of keratin formedEpidermis
315
Non keratinzed stratified squamos
Mucous membraneMoist cavities
316
Stratified cuboidal: Description and example
Secretion2 layers, top layer is definitively cuboidalSweat glands, large ducts
317
Stratified columnar
RareLarge ducts of exocrine glandsBasal layer is cuboidal, apical surface is columnar
318
Transitional
Lines excretory passages of urinary tractTransition form between stratified squamos and columnarSurface cells binucleate
319
Bladder fill and transitional epithelium
Full bladder: Surface cells stretched - squamosEmpty: Cuboidal surface domelike
320
Apical surface specialization
MicrovilliaCiliaSterocilia
321
Lateral surface specialization
Intercellular junctions
322
Basal surface specializations
Basement membraneJunctional specializations
323
Microvilli
Fingerlike extensions from apical surface (1-2um)Core of actin filamentsBrush borderAbsorptive epithelium
324
Terminal web
Horizontal web of actin, anchor microvilli
325
Glycocalyx
Extracellular coat bound to plasmalemma of enterocyte microvillia
326
Cilia
Long (5-10um) cytoplasmic extensionsNo actin core9+2 doublet formation of tubulin - axonemeFacilitate flow of fluid over epithelium
327
Intraflagellar transport
Cargo molecules loaded at base --> Use kinesin to move up --> dynein to move down
328
Primary cilia dyskinesia: Males
SterilityMale flagellum of sperm affected, cilia in testis
329
Primary cilia dyskinesia: females
Cilia in oviducts affectedFertile but increased ectopic pregnancy
330
Hydrocephalus internus
PCDEpendymal cells in ventricles play role in CSF circulationFluid accumulation in brain
331
Stereocilia
Long, immotile, branched microvilliaMale reproductive tractInner ear sensory hair cells
332
Zona occludens
Extends around entire perimeter of cell, apical area
333
Tight junctions
Fused ridges of tightly packed transmembrane proteinsRapidly formed and disassembled Block lateral movement of lipids and membrane proteins
334
Zonula adherens
Basal to zona occludensAdjacent plams membranes separated by 15-20nm gap, filled with plaque containing e-E-cadherin between
335
Macula adherens/desmosomes
points of adhesion, 25-35nm separationCadherin within space, tonofilaments anchor within cell
336
Clostridium perfringens and j(x) complexes
Attacks zona occludens J(x)Food poisoningDehydration
337
Heliobacter pylori and j(x) complexes
Binds to extracellular domain of zonula occludens in stomach --> decrease tyrosine kinase signalingGastric ulcers, carcinomas
338
Viruses and j(x) complexes
Attachment and endocytosis of reovirus to JAM protein of zonula occludens
339
Parasites and j(x) complexes
Dust mitesCleave zonula occludens proteins, loss of barrier in lungs results in exposure and immune response
340
Gap junctions (Nexus)
2-3nm separationDirect electrical and chemical communication
341
Connexon
Bridge between nexus'
342
Connexin 26
Inner ear - deafness
343
Connexin 32
PNSDegenerative disease, charcot-marie-tooth
344
Connexin 50
Congenital cataracts - blindness
345
Basement Membrane
Thin sheet of extracellular material at basal surfaceSeparation of epithelial cell and CT
346
Basal lamina
Extracellular supportive structure - only EMLamina lucidaLamina densa
347
Hemidesmosome
Anchors intermediate filaments of cytoskeleton to BMHalf desmosome
348
Lamina propria
Below BMSupport to epithelium
349
Exocrine glands
Ducts opening to surface
350
Endocrine
Release products into blood or lymph
351
Merocrine/eccrine
Release of products with cell membrane intact - Exocytosis
352
Apocrine
Part of cell membrane released (mammary glands)
353
Holocrine
Bulk release of whole cell or cytoplasm (Sebaceous glands)
354
Epithelial metaplasia
Reversible conversion of one mature cell to another typeAll epithelial
355
Cardiac muscle nuclei location
Center
356
Skeletal muscle nuclei location
Periphery
357
Cardiac muscle histological description
More redCentral nucleiLots of cytoplasmBranching
358
Skeletal muscle histological description
Nuclei in peripheryWide cellsStriations
359
Smooth muscle histological description
Many evenly scattered nuclei
360
Calcium signaling for muscle contraction
Ca increase --> Ca2+/Calmodulin complex activates Myosin light chain kinase --> activates myosin light chains --> Myosin light chain phosphatase removes phosphate from LC
361
Difference between smooth and skeletal muscle contraction
Smooth muscles twist and can lockUse less energy
362
Multiunit smooth muscle synaptic transmission
Each cell receives synapse
363
Unitary (visceral) smooth muscle synaptic transmission
Few synapses, transmitted via gap junctions
364
3 blood vessel wall components
Tunica intima: InsideTunica media: MiddleTunica adventitia: Outisde
365
Tunica intima composition
Endothelial cells and loose connective tissue
366
Tunica media composition
Smooth muscle
367
Tunica Adventitia composition
Dense irregular connective tissue
368
Vessels ranked by thickness: Highest to lowest
Artery >> Vein >> Lymphatic vessel
369
Difference between artery and vein TM
Smooth muscle in Artery
370
Capillaries composition
Endothelial cells and basement membraneNo smooth musclePinocytotic cellsTight junctions
371
Continuous capillaries
Least permeable, endothelial cells have tight junctions and no fenestrations
372
Fenestrated capillaries
More permeable, endothelial cells have tight junctions with fenestrations
373
Functions of basal laminae
Structural supportBarrier or selective filterInfluences cell polarity and differentiationPromotes and guides cell migration
374
Fibronectin
Connects fibroblasts1 geneBinding sites for many components (collagen, fibrin, cells)
375
RGD
Cell binding domain of fibronectin
376
Integrins
Protein on cells that bind to fibronectinAlpha/beta chainsSome have RGD receptorsTransmembrane signaling
377
Integrin activation
Leukocyte rolling on endothelial cells --> reaches point with activating factors (site of infection) --> signaling cascade --> integrin in active confirmation
378
Leukocyte Adhesion Deficiency
Lack of integrin Beta2
379
LAD I
Structural defects in integrin
380
LAD II
Absence of selectin ligand
381
LAD III
Defects in integrin activation
382
Brown fat location
CervicalSupraclavicularParavertebral
383
White fat function
Energy storageInsulationCushioning
384
Brown fat function
Heat regulation
385
Brown fat heat generation
Uncoupling of respirationRich vascularization spreads heat
386
Cushioning locations
Palm of handButtocksOrbit of eyeKidney
387
Hematochezia
Passage of blood through the anus
388
Melena
Black feces resulting from upper GI bleed/upstream colon
389
Peri-partum hemorrhage
Childbirth bleed
390
Gross hematuria
Blood in urine
391
Hemo-pericardium
Blood in lung/heart
392
Ecchymosis
Hematoma associated with skin or mucous membraneBruise
393
Hemostasis trio of components
1. Vasculature and hemodynamics2. Platelets3. Coagulation cascade
394
Vascular response of hemostasis
1. Vasoconstriction2. Endothelium: When broken, collagen interacts with blood, release vWF --> Platelet adhesion trigger3. Formation of platelet plug
395
Fibrinogen
Links one platelet to another
396
Coagulation Cascade
Create fibrin glue to support platelet plug until endothelium/matrix remodeling
397
Virchow's triad
Increase risk for thrombosisInjuryBlood flow: Stasis/turbulenceCoagulation pathway: hypercoagulability
398
Congenital Atresia
Valve does not form
399
Mass effect
Pregnancy or tumor squeezing veins
400
Ischemia
Hypoxia
401
Infarct
Ischemic necrosis (Death of downstream tissues due to vessel narrowing) caused by artery occlusion
402
Embolus
Detached mass carried by bloodThromboemboli most common
403
Cardiogenic shock
Heart Pump failure
404
Hypovolemic shock
Massive blood loss, fluid loss from burns
405
Enterococcus faecalis
Gram positive CocciNormal flora in gutHighly resistant, including vancomycin
406
Gram Positive Cocci
Strep. pyogenes (group A)Strep. pneumoniaeStrep. viridans (normal flora)Staph. aureusStaph epidermidis (normal flora)Group B beta-hemolytic strep: Strep. agalactiaeEnterococcus faecalis
407
Central tolerance
Deletion of self reactive clones of lymphocytes - negative selection
408
Peripheral tolerance
Lymphocyte interacts with antigen --> no subsequent response
409
Clonal anergy
T cell recognize self antigen but no Co-stimulatory signalFunctional unresponsiveness
410
Regulatory T cells
FoxP3, CD25 - markers for regulatory T-cellsInhibit T cell activationInhibit T cell effector functions
411
Activation induced cell death
Apoptosis induced by apoptotic proteinsDeath ligands
412
Receptor editing (B-cell)
New light chain rearrangement replacing original VL chain in B cell
413
Molecular mimicry
Normal foreign antigen response cross reacts with self antigen(Rheumatic fever)
414
Celiac disease HLA typing
95% DQ2DQ8Used for diagnostic exclusion
415
Multiple Sclerosis
Autoimmune response against myelin sheath --> demyelinationAnimal model: EAETransfer disease to healthy animal --> recipient gets disease
416
Insulin dependent diabetes mellitus
Insulitis in islet cells
417
Rheumatoid factor
Autoantibodies against Fc portion of IgG
418
X-linked agammaglobulinemiaBruton's
Defect in btk gene, disrupted B cell developmentPro --> pre blocked
419
Selective IgA deficiency
Deficiency in IgAAnaphylactoid rxn to blood transfusion
420
Hyper IgM immunodeficiency
Lack of CD40L (t cell help)Elevated IgM and low/no class switching to other Ig'sX-linked
421
CVID - Common variable immunodeficiency
Immunoglobulin deficiencyB cell and Ig deficiencyWide varietyRecurrent infectionLymphoproliferative diseasesAutoimmune cytopenias
422
DiGeorge syndrome
Thymic aplasia: Thymus doesn't form --> low T cell countHypocalcemia, congenital heart defects
423
Gamma chain deficiency
SCID: Common gamma chain that is subunit of cytokine receptors (IL-2, 4, 7, 9, 15)T cell and NK cell deficiencyB cell intact (but T cell count affects B cell activation)
424
Adenosine deaminase deficiency
SCID: Severe absence of T cell functionAccumulation of toxic product that kills T cellsT, B, and NK deficiency
425
Bare lymphocyte syndrome (II)
SCID: Lack of MHC class II expression (transcription factor defect)No CD4+ cells --> B cells affected
426
Tcell receptor Excision Circles
Circular genome that is lost during T cell gene rearrangement - should have large amount as child while making T cellsScreen for TREC to diagnose immunodeficiencies
427
PAMPS
Pathogen associated molecular patterns
428
DAMPS
Danger associated molecular patterns
429
PRR
Pattern recognition receptorsCell surface & Intracellular
430
Familial Mediterranean Fever
Autosomal recessiveFever and localized inflammation (skin, serosal membranes, joints)- Neutrophil infiltrationDay-weeksTypically resolve, risk of amyloidosis
431
FMF Genetics
MEFV: Encodes pyrin4 functional domains
432
PYRIN domain
Domain shared by multiple proteins involved in inflammation and apoptosisMember of intracellular PRR family- Sense microbial products --> pro-IL-1beta to active form (NALP3)
433
NALP3 associated autoinflammatory syndromes
Mutation in NACHT domain of NALP3 = 3 autoinflammatory syndromesAutosomal dominant
434
Familial Cold (Urticaria) Autoinflammatory syndrome
Urticaria 30min after cold exposure: IL-1 developmentFever, chill, malaise, joint stiffness, sweating, thirst
435
Muckle-Wells syndrome
Short episodesTemp change as triggerUrticaria-like rash: achingSensory neural Hearing lossHigher risk of amyloidosis (25% in N.America)
436
Neonatal onset multisystem inflammatory disease
NOMIDEarly onset (infancy)Rash at birth- non pruritic urticaria- neutrophilic infiltrateCNS disease- non infectious meningitis- Low IQSensory anomalies-Deafness, optic nerve atrophyArthropathy-Arthritis during flares-Bone enlargement
437
Anakinra
IL-1 blockerBinds to IL-1R blocking IL-1a and IL-1B
438
Canakinumab
Neutralizes IL-1B
439
Rilonacept
Neutralizes IL-1B and IL-1a
440
Gout
Recurrent attacks of acute inflammatory arthritis (accumulation of uric acid)Uric acid crystals are DAMPS and result in IL-1 buildup
441
Chronic Recurrent Multifocal Osteomyelitis
CRMORecurrent lytic bone lesions with swelling and painFevers, inflammation can spread to tissues
442
CRMO treatment
NSAIDsSteroidsTNF-inhibiting agents
443
TNF receptor associated periodic syndrome
TRAPS: Autosomal dominantLong duration of inflammation and feverMigratory erythematous rashMyalgiasConjunctivitis, periorbital swellingTNF binds --> initiate inflammatory response --> receptors don't shed and inflammatory response continues
444
TRAPS treatment
Etanercept: TNF receptor analog
445
PFAPA
Common in childrenRegular occurring fevers, early age of onsetCyclicAphthous stomatitis, lymphadenitis, pharyngitisNormal growth and development
446
Cyclic Neutropenia
Inherited form caused by ELA2 gene mutation21 day cycleANC
447
Severe inflammatory diseases: Cyclic/non cyclicResolve/do not resolve by puberty
Non cyclicDo not resolve by puberty
448
Omenn syndrome
2 weeks-3 monthsMany symptoms: Erythroderma, alopecia, diarrhea, lymphadenopathy, opportunistic infectionsNormal IgGHigh IgELow IgA, IgMMaternal T cells remain, expand and GVHDRAG disorderBMT therapy
449
Allergic Rhinoconjunctivitis epidemiology
20million americans10% children, 10-30% adolescents/teens
450
Quick relief medications for asthma
Bronchodilator: Albuterol, xopenex, maxair
451
Long acting bronchodilators
Salmeterol, formoterol12hr bronchodilation but no anti inflammatory effect
452
Anti inflammatory medications for asthma
Oral corticosteroids, inhaled corticosteroids, leukotriene blockersDecrease airway inflammation - long term use results in improved disease control
453
Telodendria
Branching at end of axon
454
Epineurium
Death connective tissue surrounding nerve
455
Perineurium
Surrounds bundle of nerve fibers
456
Endoneurium
Loose connective tissue, surrounds individual nerve fibers
457
Function of multipolar neurons
Motor
458
Function of bipolar neurons
Special sensory
459
Function of unipolar neurons
Sensory system
460
4 functions of glial cells
1. Surround neurons and hold them in place2. Supply nutrients and oxygen3. Insulate one neuron from the other4. Destroy and remove dead neurons
461
Oligodendrocyte
Form myelin sheath in CNS
462
Astrocytes
Induce blood brain barrier phenotypeMaintain chemical environment for generation of nerve impulsesScaffolding Scar formation
463
Microglia
Phagocytes of CNSMicroglial nodule when virus infects
464
Ependymal cells
Cuboidal to columnar cells arranged in single layer that possess microvilli and ciliaLine the ventricles of the brain and central canal of the spinal cord.
465
Sympathetic opthalmia
Ag sequestration in eye --> damage leads to released Ag --> Tgcells activated and attack antigen in both eyes
466
IFN-gamma and autoimmune diseases
IFN-gamma induces MHC class II molecules to be presented ---> MHC II may present sequestered AG which can induce a response
467
Goodpasture's syndrome
Type II hypersensitivityAbs bind to type IV collagen on basement membranes of kidney and lung
468
Classic neurotransmitters
Contained in small vesicles, located in active zone
469
Dense core vesicles
Contain neuropeptidesLocated further back from active zone
470
Synapsins
Vesicle associated proteinsTether vesicle to cytoskeleton
471
Docking complex
Voltage gated Ca channel and additional proteins
472
Vesicle storage and release
Vesicles sequestered in storage compartment and releasable compartmentCa influx moves storage vesicles to release zone, with help of Rab3A
473
Fusion pore
Similar to gap junction, opening associated with electrical signalMuch faster response
474
Synaptic vesicle recycling
Vesicles release neurotransmitters --> Fused membrane coated in dynamin and clatharin --> taken to early endosome and recycled
475
Ionotropic receptor
Ligand gated receptorDirect receptor channel coupling
476
Metabotropic Receptor
G protein mediated receptor channel couplingSecond messenger mediated receptor/channel coupling
477
End plate potential
EPP: evoked in muscle cell and triggers PSAP and muscle contractionSuper threshold for muscle contraction, safety factor150-200 quanta released
478
MEPP
Miniature end plate potential Constantly happening, spontaneous release of AChMany MEPPS can result in AP
479
Myasthenia gravis mechanisms
1. Bind to ACh receptor and block binding and receptor activation2. Promote endocytosis of ACh --> AChR degradation3. Destroy Postsynaptic surface, less AChR's
480
Lambert-Eaton Myasthenic syndrome
Presynaptic diseaseReduction of Voltage gated calcium channels (Immune attack)Weakness improves with activityTreat with aminopyridines
481
Clostridial neurotoxins
Botulinum toxin A: BotoxBotulinum toxin B: Myobloc- weaken nerve muscle 4-6monthsBind and cleave SNAP 25 (docking zone protein)
482
Clostridium tetani
Passes retrograde along nerve fibersInhibits inhibitory neurons that control spinal motor neurons and brainstem excitabilityAttacks synaptobrevin
483
Wired transmission
Direct connection between pre and post synaptic neurons
484
Volume transmission
Release site of neurotransmitter is some distance from target cellSlower onset, longer effect
485
CNS cessation of neurotransmitters
DiffusionRe-uptake into glial cells and synaptic terminal
486
Retrograde neurotransmitter
Messenger that goes from post synaptic cell to presynaptic cell and induces further neurotransmitter release
487
LTP requirement
Protein synthesis
488
Pre-synaptic inhibition
Inhibitory neuron contacts the terminal of a second presynaptic neuronReleased NT by inhibitory neuron depresses calcium current --> reduces NT release by presynaptic cell
489
Presynaptic facilitation
Facilitating neuron enhances release of NT by other presynaptic neuron
490
Squamous metaplasia: Smokers
Ciliated columnar --> stratified squamous
491
Desmoplasia
Way connective tissue respond to neoplasmsCollagenous stroma laid down by desmoplastic fibroblasts
492
Nicotine
AChR agonist
493
Physostigmine
AChE inhibitor
494
D-tubocurarine
Competitive inhibitor of AChR
495
Tetrodotoxin, Saxitoxin
Blocks Voltage gated Sodium channels
496
Conotoxin
Blocks Voltage gated calcium channels
497
Succinylcholine
AChR agonistInactivates end plate sodium channels, desensitization of AChR
498
Organophosphate compounds
Irreversible inhibition of AChE
499
4 mechanisms of Calcium level regulation in nerve terminal
1. Binding to proteins (calmodulin)2. Na symport channel3. Active transport out4. Sequestration
500
EPSP
Fast - ionotropic receptors that pass NA and KInward current = depolarization of postsynaptic membraneMagnitude proportional to amount of NT released
501
IPSP
Fast - ionotropic GABA and Glycine receptorsIncrease Cl- conductance into cell (hypoerpolarization)Or increased K permeability = hyperpolarization
502
ATP depletion
Reduced Oxygen - ischemic damageMitochondrial damageFailure of Na/K pumpDisruption of translational machinery Shift to anaerobic glycolysis --> decrease in pH
503
Elevated cytosolic Ca2+
External: failure of Ca pumpInternal: release from mitochondria/EREnzyme activationDisruption of mitochondria membrane potential
504
Oxidative stress
Reactive oxygen species: Superoxide, H2O2, hydroxyl radicalROS scavengers: Vit C and EEnzymes - superoxide dismutase, catalase, glutathione peroxidase
505
Loss of membrane integrity
ATP depletionIncreased CaIncreased protease activity
506
Protein misfolding
Unfolded protein response activatedUnresolved = apoptosis
507
Genotoxic stress
p53 transcription factor activationCell cycle arrestApoptosis
508
Necrosis
Damage exceeds repair capacityCells swell, leaky membranes, nuclear changesDue to energy failure
509
Coagulative necrosis
Injury causes protein denaturing - infarct
510
Liquefactive necrosis
Hydrolytic enzyme releaseFocal infections, brain infarcts
511
Caseous necrosis
Focal infection and immune responseTB, histoGranuloma
512
Fat necrosis
Focal destruction of fatAcute pancreatitis
513
Gangrenous necrosis
Dry: ischemia, distal limbWet: Superimposed bacterial infectionGasL Deadly form, anaerobic bacterial infection
514
Apoptosis
Intrinsic: Injury to mitochondria inducedExtrinsic: Growth factor trigger
515
Necroptosis
Hybrid of necrosis and apoptosisTNFR ligation
516
Pyroptosis
Self destructCapase-1Pro-inflammatory signals released
517
Neonatal diabetes mutations
Kir6.2SUR1
518
Kir6.2 mutation
Decrease ability of ATP to bind to K-ATP channelNo insulin release
519
SUR1 mutation
Increase Mg2+ and ADP to bindStops ATP binding
520
Myotonia Congenita
Defect in Cl- conductance, slow repolarization after AP --> chance for repeated AP's and thus constitutive muscle contractions
521
Bladder metaplasia
Transitional --> SquamousStones
522
Esophagus metaplasia
Squamous --> ColumnarReflux
523
Dysplasia
Pre-neoplastic changeCellular atypia: Aberrant mutation, enlarged nuclei, nuclear hyperchromasia
524
General somatic afferent fibers
Bring conscious/unconscious sensory memory from body wall and limbs
525
General visceral afferent fibers
Bring sensory information from visceral structures to CNS
526
General somatic efferent fibers
Innervation of voluntary skeletal muscles
527
General visceral efferent fibers
Innervation of cardiac muscles, smooth muscles, and glands
528
Dorsal root ganglions
Afferent nerve fibers
529
Dorsal horn
Entry of sensory information
530
Ventral horn
Location of motor neurons
531
Lateral Horn (Thoracolumbar)
T1-L2Location of preganglionic sympathetic neurons
532
Craniosacral preganglionic nerves
Parasympathetic originsBrainstem and S2-S4
533
Path of efferent sympathetic nerve transmission
Information from CNS --> Travel down to spinal cord --> Leave through lateral horn via ventral root --> Enter spinal nerve --> Enter sympathetic ganglion via white ramus --> Exit sympathetic ganglion via gray ramus --> Travel through spinal nerve to target
534
White ramus
Myelinated connection between spinal nerve and sympathetic ganglionOnly T1-L2
535
Gray ramus
Unmyelinated connection between sympathetic ganglion and spinal nerveAll levels
536
Path of efferent sympathetic nerve transmission (to cervical/lumbar area)
Information from CNS --> Travel down to spinal cord --> Leave through lateral horn via ventral root --> Enter spinal nerve --> Enter sympathetic ganglion via white ramus --> TRAVEL UP OR DOWN SYMPATHETIC CHAIN --> Synapse --> Exit sympathetic ganglion via gray ramus --> Travel through spinal nerve to target
537
Tyrosine --> Epinephrine synthesis pathway
Tyrosine --> DOPA --> Dopamine --> Norepinephrine --> Epinephrine
538
Neurotransmitter synthesis enzymes (Tyrosine --> Epi)
Tyrosine HydroxylaseDOPA decarboxylase D-beta-hydroxylasePNMT
539
Major mechanism for termination of NE action
Reuptake pumpUptake-1
540
Monoamine oxidase
Oxidizes NE to be degraded
541
Cocaine
Inhibits NE re-uptake into nerve terminalMore NE --> enhanced response
542
Imipramine
Tricyclic antidepressantInhibits NE reuptake
543
Tyramine
Indirectly acting sympathomimeticMimics NE activity by using NETaken up by uptake-1 pump --> oxidized by MAOIf MAO-inhibitor --> Not oxidized --> displaces NE from vesicles
544
Resperpine
Root of Rauwolfia serpentinaInhibits vesicular uptake of NE --> depletes vesicle so less NT when released
545
D-beta hydroxylase location
Within vesicle, released during exocytosis
546
Readily Reversible AChE inhibitor
Binds to active site but no covalent bond formation
547
Intermediate reversible AChE inhibitor
Covalent bond formation and then bond hydrolyzed - carbamates
548
Irreversible AChE inhibitor
Non hydrolysable covalent bondOrganophosphate
549
Regeneration
Proliferation of cells and tissue with host replacement tissueLiver regeneration after resection
550
Repair
Combination regeneration and deposition of collagen (scar formation)Dermal wound healing
551
Stimulatory control of cell proliferation and growth
Growth factors and cytokinesHormonesCell-cell interactionsCell matrix interaction
552
Inhibitory control of cell proliferation and growth
Contact inhibitionGrowth factors
553
Stages of liver regeneration
Priming: IL-6 produced by Kuppfer cells make hepatocytes competent to respond to growth factorsGrowth factors: HGF, TGF-a act on primed hepatocytesHepatocytes move from G0 to G1 phase of cell cycle
554
Kuppfer cells
Resident liver macrophages
555
Oval cells
Hepatic ductal cells which accumulate during toxin exposureReplace parenchymal cells and restore function
556
Primary union of skin incision
Clean injurySpace clots --> neutrophil infiltrate --> epithelial cell migration/proliferation --> Macrophage --> Granulation tissue forms --> Collagen begins to bridge wound ~1 week
557
Angiogenesis
Blood vessel formationNotch signaling pathway
558
Secondary union of skin
Larger wound, more inflammation, more granulation tissue fills defect, longer healing timeWound contraction reduces size
559
Labile cells
Continuously dividingEpidermis, bone marrow, GI mucosa
560
Stable/Quiescent cells
Potential to divideHepatocytes, renal tubular epithelium, endothelium, connective tissue, smooth muscle
561
Permanent cells
Unable to divideNeurons, cardiac myocytes, skeletal muscle
562
Determinants of quality of healing
Regenerative capacity, stromal injury, contamination, proliferative activity of connective tissue
563
Excessive repair
Hypertrophic scarsKeloids
564
Characteristics of benign neoplasms
Pushing, smooth borderHistology looks like normal tissueDo no metastasize
565
Malignant neoplasms
Hard tumorInfiltrating, invasive locallyLack of differentiation: anaplasiaMay extend into adjacent tissue or invade nerve sheaths (perineural invasion) and blood vessels (vascular invasion)
566
Invasion of matrix across basement membrane
Tumor cells lose cohesion --> secrete proteolytic enzymes --> Attach to extracellular matrix via receptors for laminin/fibronectin --> locomote through matrix
567
Alpha-1 receptor activation effects
Vasoconstriction
568
Alpha-2 receptor activation effect
Inhibition of transmitter release (NE and ACh)
569
Beta-1 receptor activation effects
Increased cardiac rate (SA node) and force (and output)
570
Beta-2 receptor activation effects
Bronchodilation, vasodilation Only Epinephrine
571
Beta-1 agonist activity
Increased cardiac output, HR
572
Beta-1 antagonist activity
Prevent increase in cardiac output
573
Beta-2 agonist activity
Dilate airways, decrease resistance
574
Beta-2 antagonist activity
Constrict airways, increase resistance
575
Alpha-1 agonist activity
Constrict blood vessels, increase BP
576
Alpha-1 antagonist activity
Dilate vessels, decrease BP
577
Pheochromocytoma
Tumor of adrenal gland, releases Epi and NEIncrease BP, HRHeadache, sweating, hypertensive crisis
578
Route 1 for sympathetic transmission
Preganglionic axon enters sympathetic chain (white ramus) --> synapse --> exit via gray ramus --> postganglionic axon to target
579
Route 2 for sympathetic transmission
Preganglionic axon enters sympathetic chain (white ramus) --> Travel up/down sympathetic chain --> synapse --> postganglionic axon to target
580
Route 3 for sympathetic transmission (thoracic)
Preganglionic axon enters sympathetic chain (white ramus) --> synapse --> Travel to heart via splanchnic nerve
581
Route 4 for sympathetic transmission (Abdominal)
Preganglionic axon enters sympathetic chain (white ramus) --> Splanchnic nerve to target organ --> synapse and postganglionic innervation
582
Parasympathetic preganglionic synapse location
Intramural ganglia on wall of visceral structure
583
Vagus nerve
Parasympathetic nerve which branches off to target organsInnervates GI tract up to splenic flexure
584
Pelvic splanchnic nerves
Sacral portion of parasympathetic divisionPelvic viscera, GI tract distal to splenic flexure
585
Heart muscle sympathetic vs parasympathetic
S: Increase rate/forceP: Decrease rate
586
Bladder urethra sympathetic vs parasympathetic
S: Detrusor relaxation, constriction of sphincterP: Detrusor constriction, relaxation of sphincter
587
Lungs sympathetic vs parasympathetic
S: BronchodilationP: Bronchoconstriction
588
GI organs sympathetic vs parasympathetic
S: Decreased peristalsis/secretionP: Increased peristalsis/secretion
589
Eye sympathetic vs parasympathetic
S: DilationP: Constriction
590
Glands sympathetic vs parasympathetic
S: Less secretionP: Increased secretion
591
Phenylephrine
Alpha adrenergic agonist
592
Epinephrine
Alpha and Beta adrenergic agonist
593
Scopolamine
Muscarinic receptor antagonist
594
Pupil innervation
Cholinergic and AdrenergicACh = parasympathetic = constriction = miosis *Circular muscle contraction*NE = sympathetic = dilation *Radial muscle contraction*
595
Ciliary muscle innervation
M: ContractionBeta2: RelaxationPrimarily Parasympathetic innervation
596
Vascular smooth muscle innervation
Single innervation: SympatheticAlpha1: ContractionBeta2: RelaxationNO CHOLINERGIC
597
Muscarinic receptors on endothelium
Can release NO which relaxes VSM
598
Sinoatrial node innervation
Dual innervation: Primarily parasympatheticACh & NEBeta1: Increase HR, contractilityBeta2: Only EpiM: Decrease HR
599
Atropine
Muscarinic receptor antagonist
600
GI innervation
Dual innervation: primarily sympatheticM: Contract, peristalsisBeta2: Relax, no peristalsis
601
Sphincter muscle innervation
Dual innervation: primarily sympatheticMuscarinic receptor mediated relaxation (via NO)Alpha1: Contraction, retention
602
Isoproterenol and VSM
Activates B2 --> relaxation
603
Sarin gas
AChE inhibitorIrreversible
604
Wound contraction
Reduction of size of defectMyofibroblasts3-5 days after injury
605
Wound strength
Early (week 1)- 5-10% original strength- Fibrin, re-epithelializationFirst month- Collagen content- 15%Month-years- Collagen linking/remodeling- Max 60% original strength
606
Phases of wound strength
LagRapid increase Slow increasePlateau
607
Keloids vs hypertrophic scars: Similarities
Excessive granulation tissueExcessive collagenInitial morphological similarity
608
Keloids vs Hypertrophic scarsL Differences
Keloids do not regress, recur, extend beyond injury site
609
Biological aging of cells: Increase and decrease
Increase: Organelle damageDecrease: Oxidative phosphorylation, protein synthesis, nutrient uptake, DNA repair
610
Cardiovascular aging
Intimal thickeningVascular stiffnessHypertension, atherosclerosis
611
Urinary aging
Bladder elasticity declines, glomerulosclerosisBladder control problems decline in kidney function
612
Respiratory aging
Loss of elasticity, immunityInfection, reduced exercise tolerance
613
Endocrine system
Hormone levels changeAge associated disease, diabetes, hypotension
614
Liver aging
Decreased blood flow, loss of hepatocytesDrug metabolism declines, Adverse drug reactions
615
GI aging
Gi hormone decrease, smooth muscle atrophyConstipation, Reflux, nutritional defecits
616
Trauma and aging
Inflammation and re-epithelialization is delayed
617
Cumulative damage and aging - Accumulation
Waste product accumulation: LipofuscinAdvanced glycation end products- non enzymatic addition of sugars to proteins- Affect multiple tissues-Skin collagen and lens
618
Hutchinson Gilford Progeria syndrome
Hydrocephalic appearancePremature aging lookAge associated pathology - osteoporosis, insulin resistance, CVDLamin A gene-Splice disorder --> Deletes 50 amino acidsNew protein is progerinDisrupts nuclear envelope
619
Werner's Syndrome
Autosomal recessivePremature wrinkling and graying, age related pathologyCancerMutant gene: WRN-1 (helicase)
620
Telomeres
Added by telomeraseLength shortens after division --> trigger p53
621
Resveratrol
Extends lifespan in lower organisms
622
Rapamycin
Increases lifespanEnhances progerin clearanceImmunosuppressive
623
HPV protein E6
Mimics MDM2Ubiquination and degradation of p53 protein--> loss of tumor suppressor
624
HPV protein E7
Eradicates function of RBRemove brake against proliferation
625
EBV in immune suppressed patients
Activates BCL2Prevents apoptosis
626
Chronic inflammation and cancer promotion
Release factors for cell proliferation by leukocytes or by protease digestion of ECM
627
HER2/neu
Amplification in breast cancer
628
N-myc
Amplification in neuroblastoma
629
Acute leukemias defect
Translocation
630
ZAP-70
Chronic lymphocytic leukemia
631
Chronic phase CML
Elevated WBC, eosiniphilia and basophilia
632
Accelerated phase CML
20% blasts
633
Imatinib (Gleevec)
Inhibits bcr-abl tyrosine kinaseStops leukemia
634
Familial breast cancer cause
BRCA-1, BRCA-2
635
Familial polyposis cause
APC tumor supressor
636
Hereditary nonpolyposis colon cancer cause
Double stranded DNA repair genes
637
Xeroderma pigmentosum cause
Nucleotide excision repair genesUV light exposure --> Pyrimidine-pyrimidine dimers
638
Order for cancerInitiator/promotor
Initiator first then promotor
639
HTLV I
T-cell leukemia/lymphomaCommon in Japan and Caribbean
640
SA node resting tone and effect of ganglionic blocker
ParasympatheticGanglionic blocker = tachycardia
641
Myocardium ventricle resting tone and effect of ganglionic blocker
SympatheticGanglionic blocker = Reduced contractility
642
Basic steps of wound healing
InflammationGranulation tissue formationRe-epithelizalizationWound contraction and ECM deposition
643
Stimuli for GVA (pain)
pH (ischemia/hypoxia)distention (stretch)Spasms of strong activationChemical irritantsLowering of membrane potential for stimulation
644
Granulation cell
ECMInflammatory cellsFibroblastsBlood vessels
645
Wound healing cells
MyofibroblastsSmooth muscleParenchymalLeukocytesEndothelialFibroblasts
646
Cytokines for wound healing
Platelet derived GFTGF betaBasic Fibrobalst GFEpidermal GFVascular endothelial GFIL-1,8
647
Growth factor functions
ProliferationLocomotionDifferentiationAngiogenesisSurvival
648
miRNA tumor suppressor
145Breast, colon
649
Her2/neu treatment
Monoclonal antibody
650
Perineoplastic syndrome
CushingsHypercalcemiaSIA-Dehydrogenase
651
Rituximab
Drug that acts on CD20 of B cells
