Fluid Compartments (1) Flashcards
1
Q
Total body water
A
60% of body weight
= 42 L
2
Q
ECF
A
20% of body weight
= 14 L
3
Q
ICF
A
40% of body weight
= 28 L
4
Q
Interstitial fluid
A
3/4 of ECF
= 10.5 L
5
Q
Plasma
A
1/4 of ECF
= 3.5 L
6
Q
Measurement of volume of fluid compartments
A
Dilution method
Adding tracer, allow mixing, measure concentration
Volume = Mass / Conc.
7
Q
Dye for Total fluid compartment
A
Deuterium
(Hydrogen isotope)
8
Q
Dye for ECF
A
Inulin
9
Q
Dye for Blood plasma
A
Evans-blue
(binds albumin)
10
Q
Na+ E/ICF
A
ECF: 135 - 147 mM
ICF: 10 - 15 mM
11
Q
K+ E/ICF
A
ECF: 3.5 - 5.0 mM
ICF: 120 - 150 mM
12
Q
Ca2+ E/ICF
(Total)
A
ECF: 2.1 - 2.8 mM
ICF: 100nM
13
Q
Ca2+ E/ICF
(Free)
A
ECF: 1.1 - 1.4 mM
ICF: 100 nM
14
Q
Cl- E/ICF
A
ECF: 95 - 105 mM
ICF: 20 - 30 mM
15
Q
HCO3- E/ICF
A
ECF: 22 - 28 mM
ICF: 12 - 16 mM
16
Q
Oncotic Pressure
A
Osmotic pressure of proteins
- Proteins are superosmols
17
Q
Hyposmotic / Hypotonic
A
Cell volume increases
18
Q
Hyperosmotic / Hypertonic
A
Cell shrinks
19
Q
Isosmotic urea solution
A
Eventually Hypotonic due to movement of Urea into cell (permeable) causing hypotonicity and cell to swell
20
Q
Osmolarity of most human body fluids
A
290 mOsm/L
21
Q
2 Types of Protein mediated transport
A
- Carriers
- Channels
22
Q
Carriers
A
- Slow
- Can saturate
- Active
23
Q
Channels
A
- Fast
- Can’t saturate
- Passive
24
Q
Primary vs Secondary active T
A
- Prim: Pump
- Sec: Coupled Active + Passive
25
Electrogenic vs Electroneutral T
Electrogenic T creates net charge across membrane
26
Facilitated diffusion
- Faster than free diffusion
- Passive
- Specific
- Integral pm protein
27
Aquaporins
Water transport across membrane
- 11 isoforms
- Passive
28
Special about GLUT4
Insulin dependent
(activates it)
29
GLUT 5
Transport of Fructose along with glucose
30
GLUT2 mech
Regulates glucose levels based on plasma glucose concentration, unlike GLUT1 which works constantly
31
Anion exchanger
Cl- / HCO3-
- RBCs fro CO2 transport
- Passive
- Electroneutral
- Antiporter
32
Na+ / K+ ATPase
- 3Na out, 2K in
- Electrogenic
- Inh: Ouabain
- In all cells
33
3 Ways to regulate Transporters
(in order of speed)
1) Activity (phosphorylation)
2) Trafficking (vesicle storage)
3) Expression (gene exp.)
34
Calcium ATPase
(SERCA)
Responsible for low cytoplasmic Ca levels
- Electrogenic
- SR & SER
- 2 Ca2+
35
ABC Transporter
Active transport of Hydrophobic compounds (Cholesterol, Bile,...)
- Responsible for multi-drug resistance of cells
- CFTR
36
2 Types of Exocytosis
- Constitutive: Non-regulated continuous
- Regulated secretory pathway (intracellular signalling)
37
Second messenger-gated channels
Controlled by changes of intracellular signaling molecules (cAMP, IP3)
- Sensors on IC membrane
38
VG Ca channels a1 subunit
a1 subunit forms ion pore
39
5 Types of VG Ca channels
- L-Type (long-lasting)
- T-Type (transient)
- N-Type (neuronal)
- P-Type (purkinje)
- R-Type (residual)
40
N-type VG Ca channel
For Synaptic NT release in Brain and PNS
- High activation voltage
41
T-type VG Ca channel
- SA node
- Pacemaker activity
- Low activation Voltage
42
L-type VG Ca channel
- Skeletal, SM, Myocytes Contraction
- High activation Voltage
43
Neurons Em
-70 mV
44
Skeletal muscle Em
-90 mV
45
RBC Em
-10 mV
46
Diffusion potential
Potential difference generated across a membrane when an ion diffuses down its conc. gradient
- Magnitude depends on size of con. gradient
47
Equilibrium potential (Eion)
Membrane potential when the net ion flow through an open channel is 0
48
What can we use to calc Eion
If we know ion conc. on both sides of a membrane and there is no net flow of the ions across the membrane,
= Nernst Equation
49
Relative permeability of Na, K, Cl
K: 1.0
Na: 0.01
Cl: 0.1
50
What happens if the permeability of an ion changes
The membrane potential will change in the direction of the equilibrium potential of that ion
51
Eion of ions K, Na, Cl, Ca
K: -94 mV
Na: +65 mV
Cl: -88 mV
Ca: +130 mV
52
Donnan Potential
Electric potential when impermeable ions (large molecules) create charge imbalance bw 2 compartments leading to unequal distribution of permeable ions
53
Action Potential
A spreading wave of VG Na+ Channel activation (all-or-none)
Spreads without Decrement
Rapid, Transient, Self-propagating.
54
Electrotonic potential
+ Examples
A localized change in the membrane potential in response to a stimulus.
Spreads with Decrement
- EPSP
- IPSP
- Receptor pot.
(size and duration proportional to the stimulus)
55
Receptor Potential
Change in Voltage across a receptor membrane proportional to the Stimulus Strength resulting in Inward current flow
- Sensory receptor
56
Length/Space constant
The distance over which the change in potential decreases to a factor 1/e of its maximal value
Higher S.C = Faster conduction
57
What type of signal is an AP
Digital signal
(all-or-none)
58
What type of signal is a Graded Electrotonic Potential
Analog
(electric pulses of varying amplitude)
59
How does AP form in relation to Electrotonic potential
AP is a result of Electrotonic potential which reaches the threshold voltage and stimulates VG ion channels
60
What is normal threshold potential of a cell for AP
-50 mV
61
Absolute refractory period
- Inactivation of VG Na channels
- No AP can form no matter the strength of the stimulus
62
Relative refractory period
- Hyperpolarization due to K+ channels
- Very strong stimulus needed to overcome the negative charge
63
Inhibitor of VD Na channel
Lidocaine
64
AP conduction is dependent on 2 factors
- Axon diameter (thicker = faster, R = V/A)
- Myelination (saltatory conduction bw nodes of ranvier)
65
Measure of Drug potency
EC50
Effective concentration of a drug required to reach 50% or the drug's max effect
66
Measure of Drug efficacy
Emax
Max effect which can be expected from the drug
67
Constitutive activity
Receptors which are active even in the absence of a ligand
But can still change effect when ligand is present
68
Signaling by GTP-binding protein
- GEF (guanidine exchange factor) removes GDP from G-protein, allowing GTP to bind
- GAP (GTPase activating protein) cleaves GTP to GDP, inactivating the G-protein
69
G-Protein Coupled Receptors (GPCR)
Structure
- 7 TM domains
- Heterotrimeric (a, B, y)
70
G-Protein Coupled Receptors (GPCR)
Mechanism of Action
1) Ligand binds causing binding of receptor to G-protein
2) GTP to GDP
3) a-GTP dissociates from By
4) Act on effectors
71
Gs
Act. of Adenylyl cyclase increasing cAMP
1) ATP to cAMP
2) cAMP act. of PKA
(PDE breaks down cAMP)
72
Gi/o
Inh. of Adenylyl cyclase decreasing cAMP
1) cAMP drops, PKA drops
2) K+ channel act. = hyperpol.
3) Ca2+ channel inh
4) PLA2 act.
73
Gq/11
Increase in I.C Ca2+ conc.
1) Stim. of PLC
2) PIP2 to IP3 and DAG
3) DAG activates PKC
4) IP3 increases sarcoplasmic and ER Ca2+ release
5) MLCK - muscle contraction
6) Act. of cAMP phosphodiesterase
(cAMP, PKA, inhib. of MLCK)
74
G12/13
Regulates guanine nucleotide exchange factors
1) Activation of Rho Kinase by Rho-GTP
2) Smooth muscle contraction
75
Ca2+ channels in ER (RyR)
IP3 receptors
- RyR1: Skeletal muscle
- RyR2: Cardiac receptor
- Ryr3: Others
76
B-arrestin on GPCR
1) GPCRK phosphorylates the activated receptor with Ligand
2) Receptor binds B-arrestin
3) B-arrestin uncouples the receptor from G-proteins (desensitization)
77
a1- AR
- NE > E
- Gq/11
- Increase: IP3, Ca
- SM contraction
78
a2 - AR
- NE > E
- Gi/o
- dec: cAMP, Ca
- Inc: K+
- Presynaptic inhibition
79
B1 - AR
- NE = E
- Gs
- cAMP inc.
- Heart
80
B2 - AR
- E > NE
- Gs
- cAMP inc.
- Smooth m. Relaxation
81
B3 - AR
- NE > E
- Gs
- cAMP inc.
- Adipocytes
(Thermogenesis)
82
Ion channels
- Faster than GPCR
- Uses paracrine signaling
- Neurotransmitters
83
Ach-R
Nicotinic: Na+ / K+
Inh. by Curare
(Excitatory)
84
Glutamate-R
- NMDA: Na+ / K+ / Ca2+
- AMPA, Kinate: Na+ / K+
(Excitatory)
85
GABA-R
Type A&C: Cl-
(Inhibitory)
86
Glycine-R
Cl-
(Inhibitory)
87
2 types of Cholinergic-R
- Muscarinic
- Nicotinic
88
Muscarinic Ach-R
- Activate GPCR
- Inh. by Atropine
- M1, M3, M5: Gq/11
- M2, M4: Gi/o
89
Receptor Tyrosine Kinase (RTK)
- GF, Insulin
- E.C binding site, I.C tyrosine kinase domain
90
RTK mechanism
1) Ligand binding causes dimerization
2) Autophosphorylation
3) SH2 domain of GRB2 recognizes phosphotyrosine
4) Signaling pathway
91
RTK signaling pathway
1) GRB2 recruits SOS
2) SOS activates RAS by GDP to GTP
3) MAPK produced
4) Phosphorylation of transcription factors in Nucleus
5) Cell proliferation / Survival
92
PIP3 Kinase Role
Inhibits Apoptosis pathway
1) PIP3 Kinase binds RTK with SH2 domain
2) PIP2 phosph. to PIP3
3) PIP3 recognized by PDK and PKB
4) PIP3-PDK activates PIP3-PKB
5) PKB phsophorylates "Bad" protein holding the death-inh. protein
93
How does NO synth work?
In soluble guanylyl cyclase
1) Cytosolic Ca with Calmodulin
2) Activates NOsynth
3) NO binds sGC making cGMP
4) PKG increase
5) MLCP act, MLCK inh.
94
Serine-Threonine Kinase-R
1) TGF-B (transf. growth f-B)
2) Binds type II subunit
3) Phosphorylated domain
4) Kinase activity on
5) Phosphorylation of target protein
95
Enzyme activity Linked -R
- GH receptor with no intrinsic TK activity
- Signaling mediated by JAK to activate STAT
- Gene regulation in Nucleus
- Cytokines, Prolactin, GH
96
Non-RTK associated-R
Steps
1) Ligand binding leads to JAK phosphorylation
2) Phosphorylation of receptor
3) Phosphorylation of STAT
4) Dimerized STAT enters nucleus to regulate gene expression
97
I.C Receptors
- For Hydrophobic molecules (Steroids, TH, VitD)
1) Binds Hsp90
2) NLS revealed
3) Receptor goes to Nucleus for transcription regulation
98
Thick muscle Filaments
- Contains myosin
- 1 pair of heavy chains
- 2 pairs of light chains
- Form 2 heads with ATPase
- Cross bridge: 2 heads on 1 myosin arm
99
Thin muscle Filaments
(Skeletal)
- 3 Proteins
- Actin, Tropomyosin, Troponin
100
Tropomyosin
- At rest blocks myosin binding sites on Actin
- Needs to move in order for contraction to occur
101
Troponin
- TnT: Attaches troponin to tropomyosin
- TnI: Inh. of actin-myosin interaction by blocking binding site
- TnC: Ca2+ binds here to move tropomyosin out of way allowing Myosin to bind Actin (contraction)
102
Electromechanical Coupling
Process where an electrical signal triggers Ca2+ release from SR initiating Muscle contraction
103
Electromechanical Coupling
Steps
1) AP propagates in T-tubules
2) Membrane depol. causes DHP-R change (L-VGCC)
3) RyR activated via mechanical coupling
4) Ca2+ increase, TnC activates, Contraction
104
What Decreases intracellular Ca2+
- Na+ / Ca2+ Exchanger (out)
- Ca2+ Pump (out)
- SERCA (to SR)
- PMCA
105
What binds Ca2+ in SR?
- Calreticulin
- Calsequestrin
Ca Storage and release from SR.
106
Myosin Cross-Bridge Cycle
(Sliding Filament Theory)
1) Myosin head binds Actin filament
2) Myosin does Power Stroke pulling Actin to center of Sarcomere
3) ATP binds myosin releasing it from Actin
4) ATP hydrolyzed and E used to Recock head
107
What happens when no ATP is in muscle
Rigor position
No ATP to dissociate Myosin head from actin filament causing a tight attachment and stiffness
108
Isometric Contraction
Muscle contraction without change in length of muscle
- Tension/Tone/strength increases
109
Isotonic Contraction
Muscle contraction without change in the force of contraction (tone)
- Length changes
- Constant level of force
110
Name when Isotonic and Isometric work together
Auxotonic contraction
111
Length-Tension relationship
Force of muscle contraction depends on the length of the sarcomere
112
Temporal summation muscle
When multiple stimuli are applied to a muscle in quick succession and they sum up
113
Slow Oxidative Motor units (I)
- Sustained movements (standing, posture)
- Less fatiguable
- Red fibers (myoglobin)
114
Fast Motor units (II)
- During bursting movement (jump, sprint)
- Glycolytic
- More fatiguable
- White fibers
115
Types of Muscle growth
- Lengthening
- Hypertrophy: Doubling myofibril diameter
- Hyperplasia: New fibers as a result of injury
116
Muscle fatigue
- Accumulation of Lactate in sarcoplasm, pH drop, Ca binding to TnC decreases
- Accumulation of Pi in sarcoplasm, Ca released from SR decreases, Ca sens. decreases, less a-m binding
117
Smooth Muscle
- Spindle shaped
- No sarcomeres
- No T-tubules
118
Thin muscle Filaments
(Smooth)
- Actin
- Tropomyosin
- NO TROPONIN
119
Single Unit SMC
- Gap Junctions
- Large regions contract in unison
- Characterized by spontaneous pacemaker activity
120
Multi-unit SMC
- Each cell has its own innervation
- Tightly regulated
121
Tonic contractions of SMC
Depol. does not peak beyond the electrical threshold (basal activity)
122
What channel is absent in SMC AP generation
T-type VGCC
123
3 ways to increase I.C Ca2+
- L-VGCC (primary)
- Ligand gated CC
- IP3 gated CC / RyR (SR)
124
How does contraction occur in SMC
1) Calcium binds Calmodulin
2) Ca-Calmodulin activates MLCK
3) Phosphorylates MLC increasing ATPase activity
4) Cross-bridge cycling
125
Ca2+ independent Contraction
1) G12/13 activates GEF
2) Activating Rho-GTP
3) Inh. of MLCP
4) MLCK phosphorylates
126
cGMP effects in SMC
- Activation of phosphatase
- Phosphorylation of IP3R
- Inh. Ca entry to cell
127
B2-AR effects in SMC
1) more cAMP
2) more PKA
3) Phosphorylates/inactivates MLCK
4) no contraction
128
Chemical Synapse
- Diffusion of NT
- Unidirectional
- 1-5 ms delay (to release NT)
- 20nm
- CNS & PNS
129
Electrical Synapse
- Ion transfer
- Bidirectional
- No delay
- 2nm
- CNS, PNS, SMCs, Heart
130
EPSPs
- 0.1-5 mV Depol. for milliseconds
- Ligand-gated non-selective cation channels
- Glutamate
- AMPA, NMDA, mGLU1-8
131
Metabotropic Glutamate -R
mGLU
- Mostly: Gi
- 1&5: Gq
132
IPSPs
- 0.1-5 mV Hyperpol. for milliseconds
OR - Stabilization of Em at Negative values
- Ligand-gated Cl- or K+ channels
- GABA (y-aminobutyric acid)
133
GABA receptors
- GABA-A: Ligand-gated Cl- channel (activated by Benzodiazepine)
- GABA-B: Gi-Protein coupled-R (opening of K+ channels)
134
Types of Summation of Postsynaptic Potentials
- Temporal Summation
- Spatial Summation
- Cancellation
135
Temporal Summation
2 potentials from the same origin occur together at the same time.
2 potentials add together to make a stronger one
136
Spacial Summation
2 Synapses of different origin close to each other add together to have an effect on the postsynaptic potential
137
Cancellation
EPSP and IPSP of the same magnitude added together, cancelling each other out
138
Loading of NT into Vesicles
- H+ ATPase pumps H+ into vesicle
- H+/NT exchanger takes H+ out and NT into vesicle
(Secondary Active Transport)
139
Ach synthesis
- Synthesized from Choline and Acetyl-coA by Choline Acetyl-transferase
- Into vesicle using secondary active transport of NT/H+ exchanger
140
Ach Recycling
- Ach broken down to Choline and Acetate by Ach Esterase
- Uptake of choline using Secondary active transport of Na+/Ach cotransporter
141
Depolarizing Muscle Relaxant
Agonist of Ach-R binds and can not be broken down or breaks down much slower than Ach
Causes over-activation and inactivation of the Na Channels
(Succinylcholine, Carbachol)
142
Non-Depolarizing Muscle Relaxant
Ach-R Antagonist
Binds Ach-R and blocks Na channel signal
(Curare, Turbocurarine, Pancuronium)
143
Myesthenia Gravis
NM autoimmune disease leading to muscle weakness due to auto-antibodies against nAch-R
144
Myesthenia Gravis Treatment
Neostigmine
Inhibits breakdown of Ach in NMJ so more Ach available for binding on Receptor
145
Parasympathetic Nervous System
- Long Preganglionic fiber
- Short Postganglionic fiber
- Ggl in organ
- Postganglionic fiber goes to Muscarinic Ach receptor
(CN, S2-S4)
146
Postganglionic Parasymp. Axon transmitters
- ACh
- VIP
- NO
147
Sympathetic Nervous System
- Short Preganglionic fiber
- Long Postganglionic fiber
- Postggl. use NE (usually)
- Preggl. can go straight to adrenal gland causing E (NE) release
(T1-L2)
148
What do both Parasymp. & Symp. use for signaling from Preggl. to Ggl?
ACh
149
What receptor promotes Renin secretion in the Kidney?
B1-AR
150
Blood Volume
5.5 L
151
Hematocrit
45%
152
Hemoglobin Conc.
120 - 160 g/L
153
Blood H+ conc.
10^-7.4
154
I.C H+ conc.
10^-7.2
155
Blood plasma protein conc.
7 g/dl
156
Blood Oncotic Pressure
28 mmHg
157
Conduction speed of Nerves
- A: up to 120 m/s
- B: 3 - 15 m/s
- C: 0.5 - 2 m/s (unmyelinated)
