FFM2 - Mini I Flashcards
(392 cards)
1
Q
Pharmacology
A
Study of substances that will interact with living systems via chemical processes
2
Q
Drug
A
Molecule that will bind to target to exert effect
3
Q
Prototype drug
A
First form of a drug/medication
Is used to formulate alternative forms
4
Q
Pharmacokinetics
A
What body does to drug
5
Q
Pharmacodynamics
A
What drug does to body
6
Q
Toxicology
A
Science of adverse effects of chemicals on body
7
Q
Pharmacogenetics
A
Relationship between persons genetic makeup and response to specific drugs
8
Q
What is main item that NBME tests on for medication names?
A
Generic names of medications
9
Q
Mechanism of action
A
How drug works to produce change in body
10
Q
Pharmacologic drug action
A
Consequences of drug-receptor combination
11
Q
Pharmacologic effect
A
Results of drug action
Consequences of drugs own actions
12
Q
Precaution
A
Used when medication use should be used with care and careful monitoring of patient
13
Q
Contraindication
A
Specific circumstance where medication should NOT be used
14
Q
Relative Contraindication
A
Caution needs to be used when 2 meds used together
Benefits outweigh risks
15
Q
Absolute contraindication
A
Substance can cause life-threatening and should be avoided
16
Q
Black box warning
A
Serious/life threatening risks associated with
Most serious medication warning from FDA
17
Q
Therapeutic effect
A
Beneficial consequence of treatment
18
Q
Adverse event
A
Harmful/abnormal result form medication
19
Q
Pregnancy Risk Catagories
A
A
B
C
D
X
20
Q
Which pregnancy risk catagories are adverse?
A
C
D
X
21
Q
Affinity
A
Strength of interaction between drug and target
22
Q
Potency
A
Amount of drug necessary to produce effect
23
Q
EC50
A
Concentration drug needed to produce 50% of max effect
24
Q
Efficacy
A
Largest effect achieved with drug, regardless of dosage
25
Agonist
Bind to receptor
Produce normal response
26
Antagonist
Bind to receptor
Compete and prevent binding by other molecules
Will block actions OF agonist
27
Full Agonist
Complete 100% activation of receptor
28
Partial agonist
Binding to receptor results in >0% but < 100% of activation even with high concentrations
29
Inverse agonist
Bind to receptor and will produce a response BELOW baseline response
Decreased concentration of drug
30
Competitive antagonist
Bind to same site
Lowers efficacy of medication
Decreases EC50 of medication
31
Noncompetitive anatgonist
Bind covalently to receptor
Permanent reduction of # of receptors
Irreversible
EC50 remains same; efficacy decreases
32
Selectivity
Degree to which drug acts on given site relative to other sites
33
Nonselective drug
Affects many different tissues producing range of effects
34
Selective drug
Affects single organ/system
35
Local effects of medication
Application to site of action
36
Systemic effects
Drug enters circulation and transported to cellular site of action
37
Routes of Administration:
Enteral
Oral, sublingual/buccal, rectal
38
Routes of Administration:
Paraenteral
IV/IA
IM
SubQ
Intradermal
39
Routes of Administration:
Other types
Oral inhalation
Intrathecal/intraventricular
Topical
Transdermal
Vaginal
Urethral
40
Absorption
Entering blood stream from site of administration
41
Distribution
Process which drug reversibly leave bloodstream and enters ECF and tissues
42
Metabolism
Biochemical changes to medication to facilitate elimination from body
43
Elimination
Irreversible removal of medication from body
Renal most common
44
Bioavailability
Extent to which medication reaches systemic circulation
45
Factors affecting Absorption
ph changes
Blood low
Presence/absence of transporters
First pass effect (Liver/GI metabolism)
Drug formulation
46
Factors affecting Distribution
CO and Blood flow
Permeability of capillaries
Degree of binding of drug to proteins in blood/tissue
Lipophilicity of medication
MW
47
Central compartment of body
Highly perfused organs
Heart/Liver/Kidneys
48
Peripheral compartment of body
Fat tissues
Muscle tissues
CSF
49
Instantaneous distribution within body
One-compartment
All fluids/tissues considered part of compartment
50
Delayed distribution within body
Some areas get medication faster than others...
Two-compartments
Distribution into high vascular organs then everywhere else more slowly
51
Metabolism of meds in 3 ways
1)
2)
3)
1) Active med to inactive med
2) Active med to active metabolite
3) Inactive med to active med
52
Volume of Distribution (Vd)
Fluid volume required to contain entire drug in body at same concentration as measured in plasma
53
Equation for Vd
Dose of drug/drug concentration
54
Factors affecting Vd
Drug MW
Lipophilic or hydrophilic
Ionization at pH
Protein binding
Disease states
55
Half Life (T1/2)
Time it takes to reduce plasma concentration by 1/2
56
Clearance (CL)
Volume of blood from which drug is cleared per unit of time
57
Equation of CL
CL(total) = CL(hepatic) + CL(renal) + CL (other)
58
Clearance is dependent on...
Half Life - t1/2
Volume of Distribution - Vd
59
Notable CYP-450 Interactions:
Inducers (8)
1) Carbamazepine
2) Chronic alcohol abuse
3) Modofinil
4) Nevirapine
5) Phenobarbital
6) Phenytoin
7) Rifampin
8) St Johns Wort
60
Notable CYP-450 Interactions:
Substrates (5)
1) Anto-epileptics
2) Oral contraceptives
3) Statins (EXCEPT FOR pravastatin)
4) Theophylline
5) Warfarin
61
Notable CYP-450 Interactions:
Inhibitors (16)
1) Acute alcohol overdose
2) Acetomenophen
3) Amniodarone
4) Chloramphenicol
5) Cimitidine
6) Clarithromycin
7) Erythromycin
8) Fluconazole
9) Grapefruit juice
10) Isoniazid
11) Ketoconazole
12) NSAID's
13) Omeprazole
14) Ritonavir
15) Sulfonamides
16) Valporic Acid
62
Types of Tissues
Epithelial
Connective
Nervous
Muscular
63
Characteristics of Epithelium
Avascular
Packed cells with shape/arrangement associated with function
64
Cell characteristics of epithelium
Arranged as sheets or masses
Close to one another
Have intercellular junctions
Polarized
Rest on basal lamina
65
Polarization in epithelium
Distinct surface domains
Apical, Lateral and basal surfaces
66
Classification of cells:
1)
2)
Arrangement
Shape
67
Examples of Arrangement for cells
Simple
Stratified
68
Examples of Shape of cells
Squamous
Cuboidal
Columnar
69
Features of Simple Squamous cells
Width greater than height
One cell layer thick
Nucleus protrudes into lumen
70
Location of Simple Squamous cells
Lining of BV and Lymphatic vessels
Wall of Bowmans capsule
Covering of mesentery
Lining of respiratory spaces/alveoli in lungs
71
Function of Simple Squamous cells
Diffusion
Transportation in/out of lumen
72
Special terminology for certain simple squamous epithelia
Endothelium
Mesothelium
73
Endothelium
Simple Squamous cells lining blood vessels, lymph vessels, lining of heart (atria/ventricles)
74
Mesothelium
Simple Squamous cells lining walls and covering contents of body cavities (C/A/P)
75
Features of Simple Cuboidal cells
Width, depth and height all similar
One cell layer
Centrally located nuclei
76
Location of Simple Cuboidal cells
Wall of thyroid follicle
Walls of kidney tubules (DCT)
Surface of ovary (germinal epithelium)
Interior surface of tympanic membrane
77
Function of Simple Cuboidal cells
Absorption
Secretion
Conduction involving different metabolic processes
78
Features of Simple Columnar cells
Height greater than width
One cell layer
Nuclei seen near basement membrane
79
Location of Simple Columnar cells
Intestinal tract (stomach to rectum)
Gallbladder
Uterus/cervix
Kidney collecting ducts (lower portion of)
Inner ear
Larger glands and ducts
80
Function of Simple Columnar cells
Protection
Lubrication
Absorption
Secretion
Conduction involving different metabolic processes
81
Features of Stratified Squamous cells
Multilayered
Superficial layer is squamous
Can be keratinzied/nonkeratinized
82
Location of Stratified Squamous cells
Epidermis (K)
Lining of oral cavity (NK)
Lips
Lining of esophagus (NK)
Lining of vagina (NK)
83
Functions of Stratified Squamous cells
Barrier
Protection
84
Keratinized Stratified Squamous cells seen...
Dry environment
85
Non-keratinized Stratified Squamous cells seen...
Wet environment
86
Features of Stratified Cuboidal cells
Multilayered
87
Location of Stratified Cuboidal cells
Ducts of sweat glands
Larger ducts of exocrine glands
Anal canal
88
Functions of Stratified Cuboidal cells
Barrier
Conduit
89
Features of Stratified Columnar cells
Multilayered
Basal layer appears cuboidal
Superficial layer appears columnar
90
Location of Stratified Columnar cells
Largest ducts of exocrine glands
Anal canal
Conjunctiva of eye
Male urethra
Submandibular salivary gland
91
Function of Stratified Columnar cells
Barrier
Conduit
92
Features of Transitional Epithelium
Stratified
Upper cells domed shaped
Some cells are binucleated
Apical surface will stain more pink due to actin filaments
93
Location of Transitional Epithelium
Ureters
Urinary bladder
Renal calyces
Urethra
94
Function of Transitional Epithelium
Accommodation of distention
95
Another name for Transitional Epithelium
Urothelium
96
Features of Pseudostratified Epithelium
Appearance of being stratified but is NOT
Some cells do not reach free surface
Nuclei located at different distances from basal lamina
All cells rest on basement membrane
97
Location of Pseudostratified Epithelium
Upper Respiratory Tract
Epididymis
Ductus deferens
Middle Ear
98
Special features usually seen with Pseudostratified epithelium
Ciliated or Stereocilia
Goblet cells
99
Features of Basal Lamina
Acellular
Attachment site
Components synthesized and secreted by epithelial cells
Seen with PAS and Silver salts
100
Layers of Basal Lamina
1) Lamina Densa
2) Lamina Lucida
101
Features of Lamina Densa
Network of fine filaments
102
Features of Lamina Lucida
Clear space between base of cell and Lamina Densa
Cause by artifact
103
Functions of Basal Lamina
1)
2)
3)
Structure Attachement
Compartmentalization
Filtration
104
Function of Basal Lamina:
Attachement
Connection of epithelial cells to connective tissue
105
Function of Basal Lamina:
Compartmentalization
Separates connective tissue FROM nervous, epithelial, and muscular tissue
106
Function of Basal Lamina:
Filtration
Movement of blood filtrate within kidney
Negatively charged molecules in lamina lucida/collagen fibrils in lamina densa
Regulated via ion exchange and molecular sieve
107
Composition of Basal Lamina
Laminins
Collagens
Entactins/Nidogen
Proteoglycans
108
Functions of Laminins
Possess integrins
Link basal lamina to basal plasma membrane
109
Functions of Collagens
Type IV collagen
Short filaments
Structural integrity
Molecular sieve
110
Functions of Entactin/Nidogen
Link between laminins and Type IV collagen
Supports cell adhesion
111
Functions of Proteoglycans
Bulk of basal lamina
Protein cores
Attached to cores are negatively charges GAG's
VERY EXTENSIVELY HYDRATED
Role in regulation of ions across basal lamina
112
Types of cell surface modifications
Microvilli
Cilia
Stereocilia
Lateral/Basal foldings
113
Features of Microvilli
114
Features of Stereocilia
115
Features of Lateral folds
116
Types of Junctional Complexes
Zonula Occludens
Zonula Adherens
Macula Adherens/Desmosomes
Gap Junctions
117
Features of Zonula Occludens
118
Features of Zonula Adherens
119
Features of Macula Adherens
120
Features of Gap Junctions
121
Features of Hemidesmosomes
Located on basal surface of plasma membrane
Connects basal PM to basal lamina
122
Locations with hemidesmosomes
Epithelia subjected to abrasion and mechanical shearing
Skin
Cornea
Mucosa of Oral cavity, Esophagus, and vagina
123
Composition of hemidesmosomes
Attachment plaque (plectin and BP230)
Plaque on cytoplasmic side
Intermediate filaments bind to attachment plaque
Integrins bind attachent plaque to ECM
124
Features of Focal Adhesions
Dynamic attachments
Link actin filaments to ECM proteins
125
Composition of Focal Adhesions
Actin filaments
Integrins
Laminin and Fibronectin
126
Role of Focal Adhesions
Attachment and migration of cells
127
CN-I
Name:
Sensory Function:
Motor Function:
Origin from brain:
- Olfactory
- Sensory Nerve - sense of smell
- No motor function
- Cerebrum
128
CN-II
Name:
Sensory Function:
Motor Function:
Origin from brain:
- Optic
- Sensory Nerve - sense of sight
- No motor function
- Cerebrum
129
CN-III
Name:
Sensory Function:
Motor Function:
Origin from brain:
- Oculomotor
- No sensory function
- Motor function - controls 5/7 muscles of orbit/eye
- Midbrain
130
CN-IV
Name:
Sensory Function:
Motor Function:
Origin from brain:
- Trochlear
- No sensory function
- Downward internal rotation of eye (Superior Oblique)
- Midbrain
131
CN-V
Name:
Sensory Function:
Motor Function:
- Trigeminal
- Sensory for facial sensations (pain, hot/cold)
- Motor function for muscles of mastication
- Motor function of myohyloid, anterior belly of digastric; tensor veli palantini; tensor tympani
- Pons
132
Muscles of mastication
Temporalis muscle
Massetter muscle
Lateral/Medial Pterygoid
133
CN-VI
Name:
Sensory Function:
Motor Function:
Origin from brain:
- Abducens
- No sensory function
- Motor function for lateral deviation of eye (Lateral Rectus)
- Pons
134
CN-VII
Name:
Sensory Function:
Motor Function:
Origin from brain:
- Facial
- Sensory function of taste on anterior 2/3 of tongue and sensation of ear
- Motor function of facial expressions (posterior belly of digastric; stapedius muscle)
- Pons
135
CN-VIII
Name:
Sensory Function:
Motor Function:
Origin from brain:
- Vestibulocochlear
- Sensory function of hearing (cochlear) and balance (vestibular)
- No motor function
- Pons
136
CN-IX
Name:
Sensory Function:
Motor Function:
Origin from brain:
- Glossopharyngeal
- Sensory function of taste on posterior 1/3 of tongue
- Sensory of pharynx, posterior portion of eardrum and ear canal
- Motor function of the stylopharyngeus muscle
- Medulla Oblongata
137
CN-X
Name:
Sensory Function:
Motor Function:
Origin from brain:
- Vagus
- Sensory function of pharynx and larynx
- Motor function of pharynx, larynx, and palatal muscles
- Medulla Oblongata
138
CN-XI
Name:
Sensory Function:
Motor Function:
Origin from brain:
- Spinal Accessory
- No sensory function
- Motor function of SCM and trapezius
- Medulla Oblongata
139
CN-XII
Name:
Sensory Function:
Motor Function:
Origin from brain:
- Hypoglossal
- No sensory function
- Motor function of the intrinsic and extrinsic muscles of the tongue
- Medulla Oblongata
140
Membrane potential
Differences in charges between 2 sets of ions
141
ICF or ECF:
Higher concentration of K+
ICF
142
ICF or ECF:
Higher concentration of Na+
ECF
143
ICF or ECF:
Higher concentration of Ca2+
ECF
144
ICF or ECF:
Higher concentration of Cl-
ECF
145
ICF or ECF:
Higher concentration of PO4(3-)
ICF
146
Nernst Equation
Na+, K+
~60 mV log (Concentration outside)/(Concentration inside)
147
Nernst Equation
Cl-
~60 mV log (Concentration inside)/(Concentration outside)
148
Pump Leak model
Pumps: Process using energy to move system away from equilibrium
Leaks:Process that drives a system towards equilibrium
149
Will excess Na+ outside cell change extracellular potential
No
150
Will excess K+ outside cell change extracellular potential
Yes
151
Goldman-Hodgkin-Katz Equation
It's an estimation of Vm when no net current through membrane
152
Which way do ions move?
Na+
K+
- Na will move positive charge into cells to move the internal cell potential from -70 to +60 mV (Na+ equilibrium)
- K will move positive charge out of cell to move internal cell potential from -70 to -90 mV
153
Types of graded potentials
Depolarization
Hyperpolarization
154
Electrotonic conduction
Passive process
Localized
Graded process
155
Examples of Graded potentials
Pacemaker potential in heart
Post-synaptic potentials
156
157
EPSP
Excitatory Post Synaptic Potential
Will move to threshold
Na+ will enter
158
IPSP
Inhibitory Post Synaptic Potential
Will move to hyperpolarization
Chloride enters or K+ leaves
159
Types of Graded potential summation
1) Temporal summation
2) Spatial summation
160
Temporal Summation
1 synapse can fire multiple AP's over time
May or may not actual action potential
161
Spatial Summation
Multiple synapses firing at various times intergrating at cell body to determine AP
162
Refractory Period
Period of time when cell is totally or partially inhibited from being able to respond to stimuli
163
Types of Refractory period
1) Absolute - NO AP can be generated bar none
2) Relative - able to achieve AP but requires larger amount of stimuli
164
Aqueous diffusion:
< 100 D
Small molecules
Passive
Nonselective
165
Lipid Diffusion
100 - 1500 D
Passive process
Non-selective
166
Facilitated diffusion
Passive process
Carrier-mediated
Confers selectivity
Able to be saturated
Competative
167
Bulk Transport
Passive process
<15000 but up to 16000 D
Non selective
168
Active Diffusion
Energy Dependent
Carrier dependent
Saturable
Competitive
Selective
169
Endocytosis/exocytosis
Require energy
Large molecules > 100,000 D
170
Efflux transporters
Decrease drug absorption
171
Influx transporters
Increase drug absorption
172
If pH > pKa...what is favored
Ionized H+ and A-
Unionized B and A-
173
Lipophillic
Uncharged or unionized molecule
174
If pH < pKa...what is favored
Unionized HA
Ionized BA+
175
Hydrophilic
Charged or ionized molecule
176
Ion trapping
Ionized forms of meds are more likely to undergo ion trapping - unionized forms will be readily reabsorbed back into system
177
Calculation of pH and pKa for water solubility
178
Absorption:
Sublingual
179
Absorption:
Oral
Small intestine transit time = 3-4 hrs
180
Absorption:
Rectal
Systemic and Local effects
181
Absorption:
Topical
Local effect
182
Absorption:
Transdermal
Systemic effect
183
Absorption:
Pulmonary (gases)
Systemic effects
184
Absorption:
IM
Systemic effect
185
Absorption:
IV
100% bioavailability; systemic effect
186
Absorption:
Pulmonary (aerosols)
Local effect
187
Absorption:
SubQ
Systemic effect
188
Absorption:
Intraarticular
Localized to tissue/organs
Delay systemic effect
189
Absorption:
Intrathecal
Used to bypass BBB
Administration of drugs through CSF
190
Absorption:
Intracardiac
Used for cardiac emergencies
191
Absolute bioavailability
(AUC oral)(Dose IV) / (AUC IV)(Dose oral)
192
F
Bioavailability
193
Absorption:
Intrapleural/intraperitoneal
Local effect
Decreased availability to system
194
Tmax
Time is takes for maximum [Drug] within plasma
195
Cmax
Max [Drug] reached in plasma AFTER administration of dose
196
MTC
Minimum Toxic concentration
197
MEC
Minimum effective concentration
198
Vd
(Drug Dose)(F) / CPo
199
CL total
CL hep + CL renal + Renal others
200
t 1/2
(0.7)(Vd) / CL
201
Steady State
Dose/CL
202
Loading Dose
(Css)(Vd) / F
203
Maintenance Dose
(Css)(CL)(infusion time) / F
204
CL
Rate of elimination / Plasma concentration
205
Dosing Rate
CL / Css
206
Distribution:
BBB
207
Distribution:
Placenta
208
Types of muscles
1)
2)
3)
Skeletal
Cardiac
Smooth
209
Sarcolemma of muscle types surrounded by...
Basal or external lamina
210
Composition of External Lamina
Collagen Type IV
Laminin
Perlecan
211
Composition of Skeletal Muscle Cells
- Long, multinucleated cells
- Long, oval nuclei seen at periphery of cells
- Nuclei underneath the sarcolemma
212
Origin of Skeletal Muscle
Mesodermal
213
Embryonic formation of skeletal muscles
1)
2)
3)
1) Mesenchymal myoblasts fuse and form myotubes (with many nuclei)
2) Myotubes differentiate into muscle fibers
3) Some don't differentiate - satellite cells
214
Function of muscle Satellite cells
Form new muscle fibers after injury
215
Endomysium
Surrounds muscle fiber (single muscle cell)
216
Contents of endomysium
Small BV's and small nerve branches
217
Composition of endomysium
Type I and type III collagen
218
Perimysium
Surround group of muscle fibers (fasicles)
219
Contents of Perimysium
Contains larger BV's and nerves
220
Composition of perimysium
Type I collagen
221
Epimysium
- Sheath of DCT surrounding collection of fascicles
222
Contents of epimysium
Major vascular structures and nerves
223
Composition of epimysium
Type I collagen
224
Myotendinous junctions - meeting of what 2 structures
Muscle fibers and tendon
225
At transition of muscles and tendon of myotendinous junction, fibers seen
Collagen
226
Blood supply of skeletal muscles
High vascularity
227
Reason for high vascularity of skeletal muscles
High O2 req
High energy requirements
228
What are neurovascular bundles?
Where vasculature/nerves enter muscles
229
Function of Muscle Spindles
Stretch detection in the muscle fibers
230
Structure of Muscle Spindles
Connective tissue capsule surrounding fluid filled space
Space contains thin, non-striated fibers filled with nuclei (intrafusal fibers)
231
Function of intrafusal muscle fibers
Proprioception
Detect amount and rate of length change in muscle
232
Function of Golgi Tendon Organs
Detection of tension in tendons
233
Clinical Correlation:
Polymyositis
Inflammatory disease attacking endomysium of muscles
234
Clinical Correlation:
Polymyositis S/S
Loss of muscle tisse
Progressive SYMMETRICAL proximal muscle weakness
235
Clinical Correlation:
Dermatomyositis
Inflammatory disease affecting perimysium
236
Clinical Correlation:
Dermatomyositis S/S
Progressive SYMMETRICAL proximal muscle weakness along with cutaneous findings
237
A-bands
Comprised of H-band
Area where overlap of myosin and actin fibers occur
Will remain the same with contraction/relaxation
238
I-bands
Actin filaments
Area with shorten/expand with contraction/relaxation
239
Z-line
Beginning and ending of ONE Sarcolemma unit
240
H-band
Area within A band where myosin filaments do not overlap actin filaments
241
M-line
Area where mysoin attaches
242
Thick myofilaments
Myosin
243
Structure of myosin
2 heavy chains = thin, motor proteins with heads twisted together
4 light chains = Binding sites
244
Thin myofilament
Thin, helical actin filaments running between thick filaments
245
Regulation sites of thin filamaments
Tropomyosin
Troponin
246
Structure/Function of Tropomyosin
Coil of 2 polypeptide chains situated in a groove between 2 actin strands
Will block myosin from binding to actin filaments
247
Structure/Function of Troponin:
1) Troponin T
2) Troponin C
3) Troponin I
Troponin T = attaches to tropomyosin
Troponin C = Ca2+ binding site
Troponin I = regulates myosin/actin interaction
248
Function of accessory muscle proteins
Maintain efficiency of contraction
Maintain speed of contraction
249
Examples of accessory muscle proteins (8)
Titin
𝛼-actinin
Nebulin
Myomesin
C protein
Tropomodulin
Desmin/Vimentin
Dystrophin
250
Function of:
Titin
- Anchor thick filaments to Z line
- Will prevent excessive stretching of sarcomere
251
Clinical correlation:
Dilated cardiomyopathy
Mutation of TTN gene encoding titin
252
Function of:
𝛼-actinin
- Bundle thin filaments into parallel arrays
- Anchor thin filaments to Z line
253
Function of:
Nebulin
- Runs parallel to actin filaments
- Helps anchor 𝛼-actinin to actin filaments to Z line
- Regulate length of thin filament during muscle development
254
Function of:
Myomesin
- Myosin binding protein
- Holds thick filaments at M line
255
Function of:
C protein
- Myosin binding protein
- Holds thick filaments at M line
- Will form stripes on either side of M line
256
Function of:
Tropomodulin
- Small protein attached to free part of actin
- Maintain/regulate length of actin filament in sarcomere
- Affects length-tension relationship in contractions
257
Function of:
Desmin/Vimentin
- Intermediate fibers - form lattice around sarcolemma at Z line
- Attaches Z discs to one another and to sarcolemma
- Crosslink/stabilizes myofibrils
258
Function of:
Dystrophin
- Seen beneath cell membrane
- Links laminin and agrin of external lamina to actin filaments (thru membrane)
259
260
Clinical Correlation:
Muscular Dystrophy
- Disorder where organ/tissue wastes away
- Progressive weakness and wasting of muscles
- Links actin cytoskeleton to sarcoglycan complex
- Sarcoglycan complex links to external lamina/laminin
- Laminin links to collagen fibers for endomysium
- Impairment of dystrophin causes microruptures in cell membranes - cell death
261
Function of sarcoplasmic reticulum
Concentrate and sequester Ca2+
262
Consists of...
Longitudinal tubules with enlarged region at the end (terminal cisternae)
263
Terminal cisternae associated with
T-tubules
1 T-tubule flanked by 2 terminal cisternae
264
1 T-tubule with 2 associated flanking terminal cisternae are called...
a Triad
265
Membranes of T-tubules continuous with...
Muscle fiber membranes
266
Lumen of T-tubules continuous with...
ECF
267
Function of T-tubules
Allow AP to move rapidly from cell surface into interior fiber to reach terminal cisternae
268
Composition of cardiac muscle
- Striated, single nucleus (rare for 2)
- Elongated/branched cells bound to intercalated discs
- Contraction involuntary, vigorous, rhythmic
269
Origins of Cardiac muscle
- Splanchnic mesoderm cells
- Will form primitive heart tube
- Cells align into chainlike array
- Cells form complex junctions between intercalated discs
270
Structure of intercalated disc in Cardia muscle
Cells in one fiber branch and join cells of another fiber
271
Cardiac muscle fiber components
- Single nucleus (sometimes 2, rare)
- Contain myosin/actin filaments arranged in sarcomeres
- 40% of cell volume is mitochondria
- Store FA's stored as TG's in lipid droplets
272
Components of intercalated discs
- Gap junctions
- Desmosomes
- Fascia adherens
273
Function of ______ in Cardiac muscle:
Gap junctions
Ionic continuity between cells
Allows cells to act in multinucleated syncytium
274
Function of ______ in Cardiac muscle:
Desmosomes
Macula Adherens
275
Function of ______ in Cardiac muscle:
Fascia adherens
Ribbon-link structure to stabilize non-epithelial tissue
Anchors actin filaments
276
Organells of cells located in...
Juxtanuclear region
277
Granules located in atria
Atrial natriuretic factor (ANF)
Brain natriuretic factor (BNF/BNP)
278
Function of ANF and BNF
Inhibit renin secretion in kidneys
Inhibit contraction of vascular smooth muscle
279
Function of lipofuscin granules
Pigment seen in older cardiomyocyte cells
280
Composition of Smooth muscle
- Collection of spindle cells with one central nucleus
- NO STRIATIONS SEEN
- Slow, involuntary movements
281
Origin of smooth muscles
282
Smooth muscles found where in the body?
Everywhere!
Wall of BV and airways
GIT
Pupillary dilation
Lens shape
etc...
283
Regulation of smooth muscle contraction
Electrical signals
Chemicals
Hormones
Drugs
284
Response of SM depends on:
1)
2)
3)
1) Function of tissue
2) ° of innervation from ANS
3) Expression of receptors for chemicals/hormones
285
Smooth muscle cells attached to one another via...
Desmosomes
Gap junctions
286
Types of fibers seen in Smooth muscle
Think, thin and intermediate filaments
287
Function of:
Thin filaments
Attach to dense bodies
Function like Z disc (one sarcomere from one another)
288
Function of:
Dense bodies
- Contain 𝛼-actin for thin filament attachment
- Attachment sites for intermediate filaments and adhesive junctions
289
Function of:
Intermediate filaments
Desmin/vimentin
290
Arrangement of Smooth muscle in GIT
Sheets of opposing fibers
Form inner circular layer
Outer longitudinal layer
291
Peristalsis
Contraction of inner and outer opposing layers of smooth muscle
292
Arrangement of Smooth muscle in vasculature (BV)
Seen in tunica media of blood vessels
Contracts to narrow lumen of BV
293
Seen in which types of BV's?
Medium arteries
Small arteries
294
Myoepithelial cells
- Seen in glands
- Share basal lamina of secretory/duct cells
- Contract to express contents from ducts out of gland
- Contraction mediated via calmodulin process
295
Myofibroblasts
- Possess vimentin
- Contain higher amounts of actin/myosin
- Capable of contractions
- Contract during wound healing
296
Excitation-contraction coupling
Events between generation of AP in skeletal muscle cell and release of Ca2+ from SR
297
First receptor to open to AP in skeletal muscle
Dihydropyridine receptors (DHPR)
298
Dihydropyridine is what types of receptor?
Voltage gated Ca2+ channels
299
How are DHPR arranged and where are they arranged?
1) Arranged in rows
2) On the T-tubule
300
What is the receptor associated with DHPR?
Ryanodine receptors
301
Describe Ryanodine receptors
Ca2+ release channels
302
How are Ryanodine receptors/channels opened?
1) AP signal in T-tubule causes conformational change in DHPR
2) Conformational change opens Ryanodine channels
3) Ca2+ released from SR
303
How is Ca2+ removed from intracellular concentration?
Ca2+ pump
Ca2+-ATPase pump
304
Other name for Ca2+-ATPase
SERCA
Sarcoplasmic endoplasmic reticulum calcium ATPase
305
How many molecules of Ca2+ does the SERCA pump back into the SR?
2 molecules of Ca2+ for every 1 ATP hydrolyzed
306
Steps to induce a contraction of muscle:
1) Troponin-tropomyocin complex covers myosin binding site on actin
2) Myosin is bound to ADP and Pi
3) AP signal is released to muscle membrane
4) Ca2+ released via RYN receptors/channels in SR
5) Ca2+ binds to Troponin-C; activates movement of tropomyosin from binding site
6) Myosin binds to binding site
7) Binding triggers conformational change in myosin head - power stroke occurs
8) ADP + Pi dissociate; ATP binds to myosin head
9) ATP binding causes detachment of myosin from actin; ATP immediately hydrolyzed to ADP + Pi
10) Myosin returns to resting state
307
Steps to allow for relaxation
1) Cycle continues AS LONG AS ATP/Ca2+ present at all times
2) Ca2+ re-sequestered in SR via SERCA
3) Ca2+ lvls drop; tropomyosin moves over myosin binding site on actin
308
What occurs when ATP is not available?
Myosin and actin will remain attached to one another - rigor mortis
309
What difference is there between Ca2+ binding in skeletal muscle and smooth muscle
- Ca2+ binding in skeletal muscle occurs with Troponin C
- Ca2+ bind in smooth muscle occurs with calmodulin
310
Sliding Filament Theory
Sliding part of actin past myosin generates muscle tension
311
Energy sources during muscle contraction
ATP
Creatine Phosphate
Carbs/Glycogen/Glucose
FA's/TAG's
312
Cells that generate AP in the heart
Pacemaker cells
313
Propagation of AP in the heart
SinoAtrial node
314
Difference between SR in skeletal muscle and cardiac muscle
Cardiac muscle SR is less dense and not as well developed
315
30% of heart is comprised of
Mitochondria
316
Why the high amount of mitochondria in the heart?
Increase ability for oxidative capacity and generation of ATP
317
Pacemaker cells able to undergo...
Spontaneous depolarization to generate AP
318
Reason for long duration of cardiac AP
Slow inward movement of Ca2+ thru voltage gated L type Ca2+ channels in sarcolemma
319
Composition of voltage gated L type Ca2+ channels...
5 subunits
𝛼1, 𝛼2, β, 𝛾, δ
320
Other name of 𝛼1 subunit
Dihydropyridine receptor
321
Amount of Ca2+ entering cardiac muscle cell...
Normally, small amount.
322
Absence of extracellular Ca2+
Duration of AP is shorter and unable to initiate contraction of heart
323
Ryanodine receptors in cardiac muscle - opens what kind of channel
Calcium gated calcium channel
Influx of Ca2+ initiates release OF Ca2+ from SR
324
Removal of excess Ca2+ from cardiac muscle cells
Through sarcolemma Na+/Ca2+ antiporter and Ca2+ pump
325
Type of NS stimulation on heart
Sympathetic NS
326
Types of Sympathetic receptors in cardiac muscle
β1 adrenergic
327
Sympathetic receptors are connected to which signaling pathway in cardiac muscle?
cAMP/PKA
↑ Ca2+ entry into cells
328
How often will myocardial ATP pool turnover?
Every 10 seconds
329
Which products produce 60-90% of the cardiac ATP generated?
Fatty Acid Oxidation
330
Differences between skeletal/cardiac muscle and smooth muscle
- Smooth muscle has no troponin
- Smooth muscles are not arranged in sarcomeres
331
Direct Entry of Ca2+ into Smooth muscle cell
- Enters via voltage-gated, ligand-gated, or mechanically gated channels
- Some cells (BV) have stretch activated channels
- Ca2+ entry induces Ca2+ release from SR
332
Second messenger Signaling of Smooth Muscle
- Chemical messenger binds to GPCR
- GPCR causes release of IP3
- IP3 binds to receptors on SR membrane
- Binding releases Ca2+ from SR
333
Release of Ca2+ for relaxation
- Removal of Ca2+ via Ca2+ pumps and exchangers
- Move Ca2+ into ECF and SR
334
Differences in Contraction in Smooth muscle vs Skeletal/Cardiac muscle
Smooth muscle have Pi associated with the myosin head AND with the MLC
335
Regulation of actin/myosin interaction in smooth muscle
Altering properties of myosin itself - phosphorylation of MLC
336
Phosphorylation of MLC =...
Activation of MLC binding to actin filaments
337
Enzyme that phosphorylates MLC
MLC Kinase
338
Activation of MLC Kinase due to
Ca2+-Calmodulin complex
339
Relaxation of smooth muscle due to which enzyme?
MLC Phosphatase
340
Function of MLC Phosphatase
Dephosphorylation of MLC
341
Latch State of myosin
Dephosphorylation of myosin while attached to actin
342
Control of Latch mechanism for smooth muscle
- MLCP dephosphorylation MLC
- Dephosphorylation during actin/myosin binding = latch state
- Cross bridge proceeds just MUCH slower
- Actin/Myosin complex has ↓ affinity for ATP
343
Latch mechanism is sustainable for
BV's, spinchters, and hollow organs
344
Rationale for Latch mechanism
Prolonged contractions using minimal ATP
345
Types of smooth muscle
Single-unit
Multi-unit
346
Single Unit Smooth muscle seen
Walls of hollow viscera
347
Multiunit Smooth muscle seen
Iris of eye
348
Divisions of the ANS
1) Sympathetic NS
2) Parasympathetic NS
3) Enteric NS
349
Describe the Enteric NS
Located within the GIT
Connected to CNS via parasympathetic/sympathetic fibers
350
Neural plexuses of Enteric NS
Submucosal plexus
Myenteric plexus
351
Submucosal plexus:
Where:
Function
Between submucosa and circular muscle layer
Controls secretions and GI blood flow
352
Myenteric plexus:
Where:
Function
Between circular muscle and Longitudinal muscle layers
Controls motility, contractions, and relaxation
353
Parasympathetic system located where in spinal cord?
Cranial and sacral
354
Sympathetic system located where in spinal cord?
Thoracolumbar
355
Only NT transmitted in Parasympathetic system
Acetylcholine (ACh)
356
NT transmitted in Sympathetic NS
Norepinephrine
Acetylcholine (ACh)
357
Preganglionic fibers of Para/Sympathetic NS secreted...
Acetylcholine (ACh)
358
Receptor type in the Parasympathetic NS
(pre to post ganglion)
Nicotinic receptors in the post ganglion
(nAChR)
359
Receptor type in the Parasympathetic NS
(post ganglion to target tissue)
Muscarinic receptor
360
Receptor type in the Sympathetic NS
(pre to post ganglion)
Nicotinic receptors in post ganglion
361
EXCEPTION:
Receptor type in the Parasympathetic NS
(pre ganglion to target tissue)
Seen in adrenal medulla
There are no post receptor fibers
Targer Adrenal medulla tissue directly
362
Receptor type in the Sympathetic NS
(post ganglion to target tissue)
1) Regular target tissue = Adrenergenic
2) Exception to the rule: sweat glands (muscarinic)
363
Nerves types according to what NT they release
1) Cholinergic - ACh
2) Adrenergic - Nor/Epinephrine
364
Types of ACh receptors and their specific mechanism of function
(Ligand, Voltage, GPCR, etc)
Nicotinic (nAChRs)- Ligand gated ion channel
Muscarinic (mAChRs) - GPCR
365
Types of Adrenergic receptors and their specific mechanism of function
(Ligand, Voltage, GPCR, etc)
𝛼-adrenergic; β-adrenergic
GPCR
366
Long preganglionic fibers
Short post ganglionic fiber
Short pre ganglionic fiber
Long post ganglionic fiber
367
Cells in adrenal medulla affected by pre-ganglionic secretion of ACh?
Chromaffin cells
368
Muscarinic receptors:
Stimulatory
M1, M3, M5
369
Muscarinic receptors:
Inhibitory
M2, M4
370
Stimulatory muscarinic receptors activate which type of G protein
Gq
371
Inhibitory muscarinic receptors activate which type of G protein
Gi
372
Activation of Gq protein leads to...
Increased PLC and increased Ca2+
373
Activation of Gi protein leads to...
Inhibition of Adenylate cyclase (AC) and decrease in cAMP
374
Activation of Gs protein leads to...
Stimulation of Adenylate Cyclase
Increased production of cAMP
375
Adrenergic receptors
𝛼1, 𝛼2
β1, β2, β3
376
Adrenergic receptors:
Stimulatory
𝛼1 = stimulates Gq protein
β1, β2, β3 = stimulate Gs protein
377
Adrenergic receptors:
Inhibitory
𝛼2 = stimulates Gi protein
378
Post ganglionic innervation at which sites?
Smooth muscle
Cardiac
Secretory glands
379
↑ intracellular Ca2+ stimulates...
Contraction of smooth muscle
380
↑ cAMP stimulates...on smooth muscle
Relaxation
381
↑ cAMP on cardia muscle stimulates...
↑ HR and ↑ force of contraction
382
Sympathetic responses to CVS
↑ HR = SA/AV node, β1
↑ force = β1 on atrial/ventricular muscles
↑ dilation of BV in skeletal muscles - β
↓ dilation of skin BV -
383
CO
of heartbeats per minute
384
SV
Amount blood pumped by each ventricle with each contractionSV
385
EDV
End distolic volume - amount of blood left in ventricle after diastole/relaxation
386
ESV
End systolic volume - amount of blood left in ventricle after systole/contraction
387
Calculation of SV
EDV - ESV
normal should be around 70 mL
388
Calculation of CO
CO = SV - HR
389
MAP
Mean arterial pressure
Average arterial pressure during one contraction of heart
390
Calculation of MAP
DP + 1/3 (SP-DP)
CO x TRP
391
TPR
Total Peripheral Resistance
Total resistance of BV to blood flow thry them
392
