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Lecture 1
Introduction to Physiology
&
Homeostasis
Physiological determinates of animal performance
1. Vertebrate muscle remodeling 2. Regulation of lipid metabolism
with environmental stress
Research in the
McClelland Lab
Course Syllabus available on LearnLink
****All Quiz and exam questions taken from LECTURE and LAB material
Course Syllabus available on LearnLink
0% O2!
4000-5000m 68 - 81ºC
10% O2 2000-3000m
High H2S
Hierarchical organization of the body
Cells Differentiated and specialized
2) muscle, 2) nerve, 3) epithelial
4) connective cells
Tissues Aggregate of specialized cells
2) muscle, 2) nerve, 3) epithelial
4) connective tissues
Functional units Subunits of an organs
(e.g. multiple nephrons in a kidney)
•Separates external
from internal
•Keep constant
internal envts.
•O2 in, CO2 out
Fig 1.4
The Internal Environment
42 L or 60% body wt
Sensors
Regulated Integrating center
variable
input output
Negative feedback
Effectors
Compensatory response
•Changes in the regulated variable is picked up by the sensors
•Reflex arcs = -ve feedback loop
•Set point compares input
•If s.p = input nothing happens within body
•If s.p ≠ input output causes a compensatory response using effectors, thus creating a –ve feedback
Examples: arterial blood pressure, body temperature, pH, PCO2
See Fig 1.7
Lecture 2- Jan 5
• Some are:
» Learned or required
• Most are:
» Attended by learning
Homeostatic control systems- reflex arc
Afferent Pathway: going to
Efferent Pathway: going away Set point
Stimulus or
error signal +/-
Afferent Efferent
Pathway
Regulated Integrating center Pathway
variable
receptors output
Negative feedback
Effectors
Compensatory response
•Restoration of set point never complete or exact and a persistent error signal keeps
feedback loop in operation
•Hence the term “relatively” stable in definition of homeostasis
Afferent Set Point Efferent
Pathway Pathway
T-sensitive
nerve
endings
Compensatory
Response
Fig 1.9
Intercellular communication
Integral proteins
Transmembrane integral
Peripheral protein
protein
Tight Junctions
Fluid in cristae
Mitochondria
Mitochondrial density / g
O2 consumption / Mb
Hummingbird Human
flight muscle muscle
…cont’d
• Amount of mitochondria in cells can vary
between tissues and animals
• Oxygen consumption of mouse is > than
that of elephant
• And this mouse tissues have a lot more
mitochondria than elephant
• Mitochondria is important in metabolism
and ATP using O2
Biology 2A03
Lecture 3
Protein activity
&
Cell metabolism I
Membranes
Fig 2.15
Mitochondria
•Look at different structures
•Enzymes of Krebs cycle in matrix
•ETC on cristae of inner membrane
•“power house” of cell (generates ATP)
•ATP powers physiological processes
2. Covalent modulation
• Phosphorylation and
dephosphorlyation rxn
• Red triangle (phosphate
groups) gets added to ligand
by enzyme
• Enzyme A: protein kinase
adding PO42-
• Enzyme B: phosphatase
removing PO42-
Fig 3-9, 3-10
Enzymes
• Cell metabolism: sum of all chemical reactions that
occur in cells
1. Anabolism (synthesis)
2. Catabolism (breakdown)
• Virtually every chemical reaction in the body catalyzed
by enzymes
• Often read cofactors (trace metals such as Mg, Fe, Cu,
Zn)
• Or
• Coenzymes derived from vitamins (eg., NAD+, FAD,
and coenzyme A from B vitamins)
WHY DO WE NEED ENZYMES?
•Uncatalyzed they occur at too slow rate (yrs in some cases) due to high
activation energy
•Enzymes decrease activation energy and increase reaction rates by a factor
of 105 to 1017
Fig 3.4a
• Enzyme kinetics: studying rate of reactions
S + E ES P +E
S= substrate Most important step
•
• E = enzyme (unused)
• Rates of enzymes reactions depend upon:
1. Substrate [S] or product [P] concentration (Law
of Mass Action) - ↑ in [S], rxn goes right; ↓ in [P]
rxn goes left
2. Enzyme concentration [E]
3. Enzyme activity (catalytic rate)
- Determines how quickly ligand binds to active
site and is removed
…cont’d
Change in affinity for S
e.g. allosteric modulation
Vmax 2x E
1x E
V0 ½ Vmax V0
Km Km
[S] [S]
Increasing ES complex
Vo = ([S]*Vmax)/(Km + [S])
Vmax
V0 ½ Vmax
Km = 1/affinity
Km1 [S]
Metabolic pathways
A sequence of enzyme-mediated reactions leading to a
specific product
F1 F2
F1 F2
There is no net flow, as equilibrium
The net flow is towards F2, but
Has been reached, however, there
There is flux both ways, unless
Is still flux between the two areas
It is prevented by the cell membrane
Net flux depends upon: 1) Temperature ( ^^ Temp => ^^Flux)
2) Permeability (how porous is the membrane?)
3) Mass of molecule (larger masses are harder)
4) Surface area of regions ( ^^ SA => ^^ Flux)
Diffusion:
- times (t) are proportional to the distance travelled (i.e. x^2)
F = Kp × A × (Co - Ci)
Initial concentration
Flux Area difference between
inside/outside of area of
Permeability constant diffusion
E1 E2 E3 E4
A ↔ B ↔ C ↔ D ↔ P
Na+, K+, Cl- and Ca2+ pass through the membrane with the aid of
selective transmembrane proteins channels
–Magnitude of electrical
driving force
ITC = neg charges ETC = pos charges
• depends on the valence of
the ion being driven
Fig 4.2
Electrochemical Driving Forces
Direction of ion movement depends
on balance between electrical and
Chemical forces
If these are equal the
electrochemical force is ZERO
For this example:
(TOP) Chem > Elec Forces, therefore
there is a net movement outwards
Fig 4-13
2b) Facilitated Diffusion (actually a mediated transport)
Glucose glucose
ECF = ~6mM ICF = ~1 mM
Glucose-6-phosphate
Differs from simple diffusion in
that it involves selective membrane
transporters for large or polar
molecules.
The substrate bonds, causing a
conformational change in the
protein.
Mediated transport can also
become saturated and reach
Bind substrates and undergoesmaximal flux. Simple diffusion will
conformational changes increase, and cannot become
saturated.
Fig 4-11
Fig 4-12
2c) Primary active transport
Intracellular K+ =
extracellular K+ =
Inward movement of K+
Note that an uneven distribution
Of charge is created here.
Fig 4-14
Membranes are “leaky” to ions
Ion pumping to maintain proper
Gradients, produces heat as a
by-product (up to 50% of cellular
Heat production is done this way).
300 mOsm
Hypertonic: Extracellular fluid has a greater # of osmoles of
nonpenetrating solute
Cell shrinks
400 mOsm
Hypotonic: Extracellular fluid has the lower # of osmoles of
nonpenetrating solute
Cell swells
Fig 5-10
Receptors can be intracellular: bind to lipophilic messengers
alters synthesis of a specific protein
-act as transcription factors
M R
This is an example of a
“fast” channel
Channel also acts as the
receptor
Allows channel to open quickly
and briefly
Fig 5-12
2) Enzyme-linked:Ligand-binding domain on extracellular surface and
an enzyme active site on intracellular side
Binding activates tyrosine kinase activity
which phosphorylates a protein - on tyrosine
Fig 5-13
3) G-protein-linked: (activate membrane proteins called
G-proteins and begin a signaling cascade)
G-proteins can be stimulatory (Gs) or
inhibitory (Gi)
1. Regulates a protein channel
e.g. Can open or close a
“slow ” ion channel
- Channel does not act as
receptor
2. Often activates an enzyme
e.g. adenylate cyclase to
α-subunit binds GTP
to become active produce cAMP
Fig 5-14
Second messengers
Intercellular chemical messenger which reaches the cell surface
is called the first messenger
The intracellular messenger produced by the binding of the first
messenger is called the second messenger
Act as chemical relays from the plasma membrane to the
biochemical machinery inside the cell
2
Adenylate cyclase
β GDP GTP
γ α α
GDP GTP
Amplifier
G-protein Substrate 3 enzyme
stimulatory 20x molecules
ATP Second
messenger
cAMP
Activates 4
enzyme
Protein kinase
10x molecules
5
PKA Protein Protein – P PKA
inactive + + active
ATP ADP
6
Cytosol Response in cell
Next slide
-Example of a signal transduction pathway-
Response of the cell (e.g. glycogen breakdown in liver cells)
PKA
10x molecules
active
inactive active
Phosphorylase b Phosphorylase b (100x molecules)
Kinase Kinase Amplification
of hormone signal
inactive active
Glycogen Glycogen
phosphoryase b phosphoryase a(1000x molecules)
2. Systemic circulation
Delivers O2 to tissue and organs,
NOT the lungs.
High pressure system (100mmHg)
Left ventricle Organs and tissues
Right atrium
Both have an arterial components
(blood FROM the heart) and a venous
component (blood TO the heart).
*flow through each of these circuits is
EQUAL!!!!
Fig 14-2
Blood – plasma & cells (erythrocytes, leukocytes, platelets)
1) Plasma water ~92%
Composed of:
proteins ~7% Albumin, antibodies,
Lightest l1
Hematocrit =
lt
Plasma ~54%
lt
ll
Eryhtrocytes ~45%
Plasma EPO
Production of RBC’s in
Bone marrow
Restoration of typical O2
Delivery, cycle is re-balanced
Fig 16-4
Ways to increase red blood cells
Definitions
Polycythemia: RBC’s (hematocrit) levels are too high. An
increase in viscousity makes circulation difficult.
Both of these types are cells are much less numerous in the
blood than RBC’s
Biology 2A03
Lecture 8
Circulation I
The fundamental law of the circulation
. ΔP
Q (or F) =
R
ΔP = pressure difference between 2 points in a circulation system.
P = force/area exerted by blood – generated by heart contractions.
P1 P2
.
Q
R
ΔP = MAP – CVP
= 90 – 0 mmHg
= 1 Systolic P + 2 Diastolic P
Systemic = 90 mmHg
Pulmonary = 15 mmHg
And: Q = deltaP/R
Fig 15-3 Also NOTE: Q pulmonary is equal to the Q systemic, allowing for
an even flow of blood through the system.
Pulmonary Systemic
Low pressure low resistance circuit High pressure & resistance circuit
Fig 14-5
Poiseuille’s Law
L
Q= ΔP π r 4
Q r
8ηl
ΔP
What determines vascular resistance?Since R=
constant
Q
Resistance is smaller
In parallel R1 R2 R3
than any single R
Flow = ΔP /R
CO = MAP/TPR
Vascular system
Inner radius
Arteries ~12 mm Low resistance, little pressure drop, acts as a
pressure reservoir.
microcirculation
Endothelium
(single layer of cells, which
See Fig 15-6
allows for easy diffusion.
Capillaries contain a single
layer of cells for easy diffusion
of blood.
Fig 15-5
Arteries
Muscular, highly elastic - High elastin to collagen ratio in connective
tissue
Compliance = ΔV moderate compliance to smooth out
ΔP pressure fluctuations from the heart.
Fig 15-7
systolic
PP
diastolic
Arterioles are the major site of
resistance in the circulatory system.
Fig 15-7
systolic
PP
diastolic
• Are well innervated (nerve terminal exists here) and contain smooth muscle
that contracts (vasoconstriction) or relaxes (vasodilation)
• Always some intrinsic tone (basal tone) plus tonic constriction due to basal
firing of Sympathetic Nervous System, e.g when standing
Control of vascular smooth muscle
•Affects contraction of
smooth muscle in vessel wall
Fig 15-12
Reactive hyperemic
•Triggers are same but trigger reasons are different
•Decrease in bloodflow causes metabolites to changes and trigger
an increase in bloodflow
Myogenic response
•Change in vascular resistance in response to stretch of blood
vessels in absence of any external factors
•Regulate bloodflow to be constant in tissues in phase of
stretching the vessel
Increase in blood
entering the tissue
Fig 15-14
Table 15-2
Extrinsic controls
SNS
•Arterioles highly innervated and have α-adrenergic receptors (post-
synaptic) which trigger vasoconstriction through NorEpis
•Changes above or below tonic constriction (nerves always active)
•Important role in controlling whole body arterial blood pressure
Vasodilator hormones
Fig 15-8
Capillaries
•Thin walled tube of endothelial cells
•Permeate most tissues and cells (any cell in body) generally within
1mm from a capillary
•Small in radius but networks have large surface area ~ 10-40 billion
capillaries for a combined surface area of 6000m2
Important for:
1. Exchange of materials between
blood and cells.
2. Normal distribution of ECF
(composed of plasma & ISF)
arterial
PCAP= 38 mmHg PCAP= 16 mmHg
venous
π CAP= 25 mmHg π CAP= 25 mmHg
NFP +
Osmotic Pressure
NFP -
Arterial Venous
See Fig 15-18
end end
Table 15-3
Biology 2A03
Lecture 11
Circulation V
O2, CO2 1) Continuous capillaries
-More common type
plasma
-Small spaces (H20-filled cleft) between
proteins endothelial cells
-Very permeable to lipid soluble molecules
-Less for water soluble solutes & proteins
cleft
Endothelial cell (passage restricted to H20-filled cleft)
-Proteins too large to pass through clefts
Na+, K+ 2) Fenestrated & sinusoidal capillaries
O2, CO2 -Fenestrations can be large enough to
allow large proteins or entire cells pass
proteins (e.g. WBC)
-Highly permeable capillaries
Intracellular -Liver – plasma proteins synthesized
gap
(e.g. albumin)
Fenestrations -Bone marrow – blood cell production
(pores)
See Figure 15.16a+b
Figure 15.17
Bulk Flow
Capillary membranes freely permeable to H2O and small solutes
PIF=1 PIF=1
+12 mmHg π IF=0 filtration -10 mmHg
absorption π IF=0
Blood pressure
pressure
NFP +
Osmotic pressure
NFP -
Arterial Venous
See Fig 15-18
end end
Table 15-3
Filtration ~ 20L / day
Absorption ~ 17L / day
Filtration usually exceeds
absorption with 3-4L entering IF
(= total plasma volume !)
This fluid is returned to the
circulatory system by the
lymphatic system
Lymph flow = ~4L/day
Veins also have one-way valves that ensure movement towards the heart
Fig 14-8
Two cell types display autorhythmicity: Spontaneously generate
action potentials (AP’s)
2) Pacemaker Cells
Determine the rate the heart beats
Located in 2 regions:
i) Sinoatrial node (SA) ii) Atrioventricular node (AV)
SA has a higher intrinsic rate (70 impulses/min) than the AV node
(50 impulses/min).
Can take over if SA fails or transmission to
AV is blocked
Fig 14-11
3) Conduction fibers (Bundle of His & Perkinje fibers)
Rapidly conduct (4m/s) AP generated by the pacemaker cells
Cell-cell rate through gap junctions is 0.4m/s
The heart consists of 2 syncytiums (atriums and ventricles)
connected by conduction fibers
Fig 14-9
Autorhythmic Cells
Lecture 12
Circulation V
Mean arterial pressure (MAP) = CO x TPR ΔP = Q x R
The Heart hr x SV
**Know functional anatomy and bloodflow patterns (see p421-422)
Composed of 3 layers • Outer epicardium (connective tissue)
• Myocardium (muscle)
• Endothelium (extends throughout the CVS)
Fig 14-6
• Semilunar valves
– Located between the ventricles and arteries
– Aortic semilunar valve is located between
the left ventricle and the aorta
– Pulmonary semilunar valve is located
between the right ventricle and the pulmonary
trunk
– Function similar to AV- make blood flow in
one direction and prevent it from flowing in
opposite direction
Fig 14-7
Cardiac muscle
Composed of 3 cell types:-
• Contractile cells: majority of cells (99%) have properties of skeletal
(straited-actin and myosin) and smooth muscle (gap junctions)
• All cardiac cell are interconnected (as a syncytium) through Gap Junctions-
protein channels linking cytosols-small in diameter (electric current)
• Concentrated at intercalated disk which contain connections that hold the
cells tightly together and resist mechanical stress (desmosomes)
• Sarcomeres are units of myosin and actin
Fig 14-8
Two cell types display autorhythmicity: Spontaneously generate
action potentials (AP’s)
2) Pacemaker Cells
• Determine the rate of heart beats
• Located in 2 regions:-
Fig 14-11
3) Conduction fibers (Bundle of His & Purkinje fibers)
•Rapidly conduct (4m/s) AP generated by the pacemaker cells
•Cell-cell rate through gap junctions in only 0.4m/s
•The heart consists of 2 syncytiums (atrium and ventricles)
connected by conduction fibers
Fig 14-9
Autorhythmic Cells
4
•AP enters a network of branches along the ventricle
muscle: Parkinje Fibers
•Impulse travels through ventricle from apex
towards valves
•Ventricles have coordinated contractions
Regulation of heart rate (hr) – both rate and flow are regulated
•Heart rate affected by changes in rates of AP generated by pacemakers
Temperature:
•directly alters the intrinsic rate of the SA node, changes hr by
156 bpm/oC
•e.g. 1 degree fever hr is ~85bpm
Regulation of stroke volume
•Volume ejected by ventricles with each heartbeat = stroke volume (SV)
•SV= end diastolic volume (EDV) – end systolic volume (ESV)
If EDV ↑ then SV ↑
EDV
If ESV ↑ then SV ↓
SV
Ejection fraction = SV
EDV ESV
~67% at rest, increases during exercise
p438
~33% of blood still left in heart
Biology 2A03
Lecture 13
Circulation and Kidney I
Summary of cardiovascular due to increased CO & large
changes during mild exercise decrease in skeletal muscle Resist.
- active hyperemic Beta2-
vasodilation
due to large increase in Heart Rate
– Following
hemorrhage:
• Baroreceptor reflex
• Increase in
sympathetic
activity
• Decrease in
parasympathetic
activity
– Result
• Reflex
compensation
Figure 15.27
Figure 12.59
Baroreceptor
reflexes
Baroreceptor reflexes
also facilitate a short term
partial restoration of
blood plasma volume by
reabsorbtion of fluid from
interstitial space and
lymph
kidney
Ureter
undergoes wavelike
contractions of smooth
muscle.
Bladder
smooth muscle with gap
junctions.
urethra
NOTE – all smooth muscles have gap junctions Fig 19-1
THE URINARY BLADDER
ureters
Fig 19-22
urination
Biology 2A03
Lecture 14
Kidney II
ANATOMY OF A KIDNEY
Cortex
Medulla
pyramid
t
renal
t
pelvis
t medulla cortex
t
ureter Nephron
Capsule (outer Uses circulation
tissue) To filter waste
Distal convoluted
tubule Proximal tubule
Common
collecting Loop of Henle…loops into the
duct medulla…important point, will be
covered later.
Fig 19-3
Glomerular
GFR = Glomerular filtration Efferent
Filtration Rate arteriole
Vasa Recta
To Renal Vein
This system uses
Capillaries to help filter
stuff in and out
Fig 19-6
Nephron Components - Blood side
• Peritubular Capillary Bed & Vasa Recta = 2nd capillary bed, site of
reabsorbtion (selective transport from tubule to IF, recovery) &
secretion (selective transport back to tubule, waste disposal)
2 3
1 Excretion
• Glomerular Filtration
passive due to Starling-Landis forces.
2. Tubular Reabsorption
Afferent (a) Many active transport processes for
Arteriole ions and nutrients.
(b) Passive diffusion (ions/nutrients)
Plasma may contain things and osmosis (H20)
that cannot go through the (c) Starling-Landis Forces.
Bowman’s capsule therefore
3. Tubular Secretion
Fig 19-7 tubular secretion =>
Mainly by active transport
1. Glomerular Filtration
• A volume equivalent to 20% of the plasma flowing
through the glomerular capillaries is filtered, forming
the primary urine collected into Bowman’s capsule.
• This “filtrate” contains a representative sample of
everything in the plasma except proteins (& protein-
bound substances)
- M.W cutoff ~ 68,000; smallest plasma protein = albumen
~ 69,000 (albumen is too large to be filtered/secreted)
• Glomerular Filtration Rate = GFR = 180 Litres/day
Efferent
arteriole 125 mL/min
podocyte
Foot processes
Fenestrations/slit pores
Allow for movement of
Proteins under a certain
Specified M.W. (68K Da)
fenestration
Endothelial cell
Glomerulus membrane Basement membrane
(filtration barrier)
Epithelial cell (podocyte)
Fig 19-8 Slit pore
Filtration Barrier
Bowman’s Capsule
Filtration Barrier at
M.W ~ 68,000
• podocyte slit pores
• basement membrane
matrix - negative
charge repels proteins
• endothelial fenestrae
Glomerular capillary
Lecture 15
Kidney III
Renal corpuscle
podocyte
Foot processes
Filtration slit
fenestration
Endothelial cell
Basement membrane
Glomerulus membrane
(filtration barrier) Epithelial cell (podocyte)
Fig 19-8
Slit pore
(between podocytes)
Filtration Barrier
Bowman’s Capsule
Filtration Barrier at
M.W ~ 68,000
• podocyte slit pores
• basement membrane
matrix - negative
charge repels proteins
• endothelial fenestrae
Glomerular capillary
1. Glomerular Filtration
Starling -Landis Forces
involved in glomerular filtration
PBC
PGC
PiGC
PiBC
CCD
Some Patterns of Renal Handling
Filtered & additionally Filtered & largely but Filtered & completely
secreted so totally not completely and reabsorbed, ie most
cleared from blood - reabsorbed nutrients, such as
e.g. PAH = Para- - e.g. H2O, ions, etc glucose, amino acids
amino hippuric acid
Reabsorption Barrier
GFR Cinulin
aquaporins
100mOsm
•No water reabsorption (in this
300mOsm 100mOsm scenario)
1400mOsm 100mOsm
Regulation of NaCl and H2O by the Kidney
100mOsm
•water reabsorbed (in this
water
scenario)
300mOsm 300mOsm
water •Urine has high osmolarity and low
600mOsm 600mOsm volume
water
1000mOsm 1000mOsm
water
1400mOsm 1400mOsm
Regulation of NaCl and H2O by the Kidney
H2O Reabsorption – Regulation by ADH
•Ant diuretic hormone (ADH), a small peptide also known as vasopressin,
released from the posterior pituitary gland by neurosecretory cells that originate
in the hypothalamus
Low O.P High O.P
ADH
water
cAMP/PKA pathway
water
water
Aquaporin 3
Ethanol
(inhibits this)
•Dehydration
•Brain shrinkage
HANGOVER
Regulation of NaCl and H2O by the Kidney
Na+ Reabsorption and its Regulation by Aldosterone
-Na+ reabsorption is coupled to K+ secretion
-Aldosterone is a steroid hormone released from the
adrenal cortex in response to low NaCl in ECF
[Na+] [Na+] [Na+]
receptor
Na+ aldosterone
K+
Na+
Na+ K+
Na+/K+
K+ ATPase
Function of PNS:
Conducts information from external and internal
sensors to the CNS (afferent division) AND from the
CNS to effector organs that are usually muscles and
glands (efferent division).
Efferent division of PNS
-2 Parts:
1) somatic nervous system: motor neurons that
regulate skeletal muscle contractions. Only Excitory
information which causes voluntary action.
2) autonomic nervous system: neutons that
regulate internal organs and structures ( smooth
muscle, cardiac muscle, glands, etc)
Both excitatory and inhibitory information. Involuntary
activity.
Sensory/receptor
Effector organs
Structure of a Typical Neuron
Dendrites: numerous small
Signal Direction branches, receive most of
incoming information from other
neurons via synapses. Results in
Graded Potentials (GP’s).
Cell body or soma: contains most
organelles, metabolic functions.
.
Axon hillock: trigger zone, fires
APs as a result of summation of
GPs. Site of most integration
Axon: thick process, rapidly .
conducts outgoing information
coded as AP’s
Terminals: make synapses with
other neurons or effector cells.
Two neurons communicating:
2.interneurons
Sensory/receptor
1. Afferent neuron (input)
1. Multipolar: most
common neuron, multiple
projections (1 axon, the
rest are dendrites).
2 Cell Types:
B) Glial Cells
- supportive, nutritive, & protective cells of the nervous
system, but NOT directly involved in signal transduction.
These cells insulate > 99% of the distance along the axon.
Nodes of Ranvier occupy < 1% of the total distance.
Kyelin sheath insultates the diffusion of ions, reducing
interference in the signal being sent.
APs are rather slow events involving diffusion of ions.
However, APs can leap at the speed of electricity (~
instantaneous) from one Nodes ot the next Node by saltatory
propagation.
AP conduction velocity may be accelerated up to 1000x by
saltatory propagation.
3 Basic Principles of Membrane Potentials
Depolarization
(membrane Na+ Equilibrium Potential
becomes more
positive)
Repolarization
(return towards
resting spot)
Excitatory, Na+
Inhibitory, K+, Cl-
threshold threshold
Fig 9-8
GPs versus APs
Action Potentials (A.P.’s) result from large local changes of
GNa+ & GK+ (GCl- does not usually change) which occur once the
threshold potential is passed by summation of G.P.’s.
A.P’s only occur in cells where there are “excitable membranes”
==> membranes possessing voltage gated Na+ & K+ channels ==>
in addition to the regular leakage Na+ & K+ channels
GNa+.
~1 millisecond
[Ca2+] = 10-3M
[Ca2+] = 10-8M
Presynaptic
inhibition
2. Cellular respiration:
e.g. C6H12O6 +6 H2O+ 6O2 ===> 12H2O +
6CO2 + 38 ATP
Metabolic Pathways – ATP Synthesis
One of the major roles of metabolic pathways is to convert the
energy in food (stored as fuel) to ATP to power cellular functions
O2 .
Fig 3.19 O 2-
10 enzymatic steps
Fig 3-22
Aerobic metabolisms of:
ATP CO2
Carbohydrates: Glycolysis + oxidative phosphorylation
Glucose 2 pyruvate 2 ATP & 2 NADH + H+ 2+6
2Pyruvate 2 acetyl-CoA 2 NADH + H+ 6 0
2+18+4 4
2 acetyl-CoA Kreb’s Cycle 2 ATP, 6 NADH + H+
2
& 2 FADH2
3ATP / NADH + H+, 2ATP / FADH2 38 ATP
Short-term regulation
ATP
Phosphocreatine (PCr)
ATP stores work
Glycogen ADP + Pi Movement
Membrane transport
Long-term regulation Molecular synthesis
Oxidation of:
Glucose and Glycogen
Fats
Proteins
Short-term regulation of [ATP]
0-10 seconds
ATP hydrolysis and Phosphocreatine
buffering
PCr + ADP + H+ ATP + creatine
CPK
4 to 120 seconds
Glycolysis
Glucose + 2Pi + 2ADP
2lactate + 2ATP + H2O
Oxygen required
1. Gas exchange:
movement of O2 from environment to
cell (mitochondria) & movement of CO2
in opposite direction
2. Cellular respiration:
e.g. C6H12O6 +6 H2O+ 6O2 ===> 12H2O +
6CO2 + 38 ATP
Anatomy of the respiratory tract
Conducting zone -
no gas exchange
between air & blood
here
Respiratory zone
Fig. 17-2
Biology 2A03
Lecture 23
Respiration I
Anatomy of the respiratory tract
Larynx
trachea
Conducting zone -
Primary no gas exchange
Bronchi between air & blood
Secondary here
Bronchi
Tertiary
bronchi
Respiratory zone
Alveolar sac
Respiratory
Alveoli
bronchioles
Fig. 17-2
Anatomical features
Little cartilage or
smooth muscle – allows
gas exchange with blood
Diffusion rate = K x A x ΔP
T
T: Thickness
A: Surface Area
K: Permeability Gas Constant
Intrapleural fluid
Muscus, negative pressure
Parietal pleura
attached to thorax
Visceral pleura
attached to wall of lungs
The flexible, lubricated connection created by the negative intrapleural space
ensures that when thorax changes size during breathing, the lungs will follow
Fig 17-9
Breathing Cycle
Inhalation - active phase during both rest & exercise
•External intercostal muscles pull ribs out & up
•Diaphragm shortens and moves down
•Due to elastic recoil of thoracic & •Internal intercostal muscles pull ribs
lung components in and down
Thoracis pressure
Biology 2A03
Lecture 24
Respiration II
Technique used to measure air volume
Spirometry
Spirometer record
Tidal Volume = amount of air breathed in and out on a single breath ~ 0.5 L
Inspir. Res. = max. amount that can be inhaled above normal inhalation ~ 3 L
Expir. Res. = max. amount that can be exhaled beyond normal exhalation~1.5L
Resid. Vol. = amount left inside, cannot be exhaled even with max. effort ~ 1L
Insp. Capacity = tidal volume + insp. reserve ~3.5 L
Functional Residual Capacity = exp. reserve + residual volume ~2.5 L
Vital Capacity = exhale maximally, then quantify max inhalation ~ 5.0 L
Total Lung Capacity = measured after maximal inhalation , ~ 6.0 L
Minute Ventilation = total air flow into (and out of) the respiratory system per minute
Dilution Factor = (300 mL new + 2500mL old)/ 300 mL new = 9.3 times (
dilution facto
==> Alveolar O2 is much lower , & alveolar CO2 is much higher , than in outside air
==> Alveolar O2 & CO2 values become closer to those in outside air during exercise
when tidal volume increases & anatomic dead space remains unchanged
Minute alveolar ventilation = f x (VT – VD)
Anatom.
dead
space
gets
= (500ml x 12breaths) – (150ml x 12 breaths)
pushed
into
150
alveoli
= 4200ml/min instead of 6000 without VD
2 x f = 8,400 mL/min.
2 x VT = 10,200 mL/min.
Table 17-1
Partial Pressure- a measure of the thermodynamic
activity of gas molecules
diffuse
Gases dissolve according to their partial pressures, not
react necessarily according to their concentrations
.
Dalton’s Law:
Total pressure = sum of partial pressure
Room air: Total Pressure = PN2 + PO2 + PCO2 + PH2O
[1 mole of any gas occupies about 22.4 L @ STP (standard temperature &
pressure]
Note: the same principles apply to N2 (mole fraction = 79%), we generally pay little
attention to N2 as it is an inert gas
In a fluid phase, situation is more compl
Partial pressure of a gas in a fluid is equal to the partial
pressure of that gas in the air phase with which the fluid is in equilibrium (real or
theoretical equilibrium)
Henry’s Law = concentration of a dissolved gas is proportional to the partial pressure &
to the solubility coefficient
The capacity of water to hold O2 ( 7 mL/ 1000 mL water) is much lower than the
capacity of air to hold O2 ( 210 mL/1000 mL air)
Lecture 25
Respiration III
PO2
Alveolar partial pressures are
All in 160 PCO2 Alveolar air very different from outside
mmHg 0.3
(Torr)
air
100
40
Pulm artery Pulm veins
The partial pressures are the same
100 between compartments. Where the
40 46 40
changes occur are @ the alveoli and at
the capillaries, where diffusion can
cause a change in the gas content of
the blood. NEED TO KNOW THESE
PARTIAL PRESSURES!!
Systemic veins
These areas of diffusion have
100 significantly different pressures
40 46 Systemic arteries 40 compared to the previous compartment
Fig 16-3
Hemes Globins
P P + P P P
X H+ X H X H+ X H+ X H+
O2 Fe 2+ - - - - - - - - - - - - - --- - CO2
O2 Fe2+ - - X- - - X- - X- - - -X - -X - - - - CO2
Hemes Globins
P P + P P P
O2 - X H+ X H X H+ X H+ X H+
Fe 2+
- - - - - - - - - - - - --- - - NH2 CO
2
O2 Fe2+ - - X- - - X- - X- - - -X - -X - - - - - NH2 CO
2
- 1st O2 helps the 2nd, & the 2nd helps the 3rd; 4th is not helped
4x O2
Hb Hb(O2)4
(Product =
% Hb-O2)
Fig 18-8
(driving force)
Loading point in pumonary capilaries
200
150
100
Venous
reserve
50
PvO2 PaO2
0
Fig 18-8
Situation at rest
Important “design features” of the sigmoidal curve:
• Flat region at top provides an important safety margin
for O2 loading during:
-high altitude exposure
- respiratory diseases
- shift in blood curve to right during exercise
2. Knee and steep part is strategically located to facilitate
a greater O2 unloading during exercise with only a
relatively small decrease in systemic tissue PO2 and
therefore in PvO2
@ 40 torr ==> ~75% Hb-O2
@ 20 torr ==> ~35% Hb-O2
So a small decrease in PvO2 creates a large increase in O2
unloading during exercise .
PvO2 decreases because of increased consumption
(increased metabolic rate) in the systemic tissues.
This is helped by 3 additional factors during exercise:
Hemes Globins
P P + P P P
O2 - X H+ X H X H+ X H+ X H+
Fe 2+
- - - - - - - - - - - - --- - - NH2 CO
2
O2 Fe2+ - - X- - - X- - X- - - -X - -X - - - - - NH2 CO
2
pH 7.6
pH 7.4 PCO2 = 55 Torr
P50
Loading pt.
During exer.
pH 7.6
pH 7.4 PCO2 = 55 Torr
Hemes Globins
P P + P P P
O2 - X H+ X H X H+ X H+ X H+
Fe 2+
- - - - - - - - - - - - --- - - NH2 CO
2
O2 Fe2+ - - X- - - X- - X- - - -X - -X - - - - - NH2 CO
2
pH 7.4
PCO2 = 55 Torr
pH 7.2 Temp = 39ºC
Loading
point during
exercise
pH 7.6
pH 7.4 PCO2 = 55 Torr
PO2 (torr)
Biology 2A03
Lecture 27
Respiration V
CO2 Transport in Blood
There is a lot more CO2 than O2 in the blood
10 % - physically dissolved in plasma and RBC cytoplasm
30% - chemically combined with hemoglobin (Hb) as
carbamino-CO2
60% - as the HCO3- ion, mainly dissolved in the plasma
carbonic
anhydrase
CO2 + H2O <====> H2CO3 <====> H+ + HCO3-
X
slow fast
Buffered Moves into plasma in
by Hb exchange for Cl-
Fig 18-11
So the Bohr Effects (and temperature effects) are not
just restricted to exercise.
Even at rest, small H+ & CO2 Bohr effects and temp. effects
shift the O2 dissociation curve slightly to the right in the
systemic capillaries, .
Apneustic Pneumotaxic
center center
Stimulates inhilation Terminates inhilatio
Rhythmicity center
Autorhythmicity and inhibit each other
I neurons x x E neurons
Fires during Fires during
Inhilation exhalation
Spinal cord
Ventilatory muscles for inhalation
Fig 18-15 (Diaphragm and intercostals)
Central Regulation of Ventilation
Apneustic and pneumotaxic centers: in pons sets pattern
and depth of breathing
I and E neurons of the rhythmicity center: in medulla set
the rate of breathing
Activity of the whole “respiratory control center” is
affected by:
-Movement and position receptors in limbs (joint-tendon receptors)
-Stretch receptors in windpipe
-Plasma hormones (e.g. epinephrine increases ventilation)
-Plasma K+, lactate
Peripheral chemoreceptors: monitor PaO2, pH, PaCO2
Central chemoreceptors: monitor PaCO2 (arterial)
Central Chemoreceptors
Figure
Central Chemoreceptors
Central chemoreceptors are the most important controls
of breathing
Located in the medulla near the rhythmicity centre and
monitors PCO2 only
Actually monitors the pH of the ECF (CSF) and reflects
the PCO2 of the CSF
Even slight increase from a setpoint of PaCO2= 40.5
Torr will cause CSF pH to decrease and stimulate
ventilation (and vice versa)
Every breath is triggered by a slight increase in PaCO2
Peripheral (“Arterial”) Chemoreceptors
Carotid
Chemareceptors
Peripheral chemoreceptors
(H+ does not easily cross
blood brain barrier)
Hyperventilation decreased PCO2
and therefore H+
Fig 18-19
2. CO2/HCO3- system:
H+ + HCO3- CO2 + H2O
OH- + CO2 HCO3-
The protein and CO2 buffer systems are in equilibrium with
each other, & with all other less important buffer systems
(e.g. phosphate, ammonia) - by the isohydric principle.
c.a.
However: [H2CO3] <===> Dissolved [CO2] = PaCO2 x aCO2
constant constant
constant
Regulated by breathing ~ fast
pHa = ~ 6.1 + log [HCO3-] 24 mmoles/L
40.5 torr * 0.03 mmoles/L
PaCO2 x aCO2
The log stuff is approx 20 normally)
pHa = 7.4
*
pHa is regulated at 7.4 by keeping [HCO3-] at 20
PaCO2 x aCO2
Respiratory acidosis - PaCO2 is too high (therefore pHa too
low) due to hypo-ventilation.
-If it’s a chronic effect, kidney slowly compensates by
accumulation of HCO3- (excreting H+).
======>
The Henderson-Hasselbalch Equation
(H. Smith (1954) - “a most useful monument to human laziness”)
regulated by metabolism & kidney -slow
~constant ~constant
constant
regulated by breathing -fast
pHa = ~ 6.1 + log [HCO3-] 24 mmol/L
*
pHa is regulated at 7.4 by keeping [HCO3-] at 20
PaCO2 x aCO2
Respiratory acidosis - PaCO2 is too high (therefore pHa too
low) due to hypo-ventilation.
-If it’s a chronic effect, kidney slowly compensates by
accumulating HCO3- (excreting H+)
e.g. TH
estrogen
Adipose tissue
e.g. leptin
testosterone
3 Classes of Hormones
1. Amines (derived from a.a.
synth - Adrenomedullary hormones
(catecholamines):
Dopamine - n/t & hypothalamic
1 hormone which
e.g. TH
estrogen
Adipose tissue
e.g. leptin
testosterone
3 Classes of Hormones
1. Amines (derived from a.a. tyrosine, tryptophan):
synth - Adrenomedullary hormones
(catecholamines):
Dopamine - n/t & hypothalamic
1 hormone which inhibits prolactin
secretion
Norepinephrine & epinephrine -
n/t’s & adrenomedullary hormones
2
Other amines:
- Serotonin (5-hydroxytryptamine) -n/t
3 & hormone derived from tryptophan -
involved in sleep, surpressing stress
responses, & moods.
4 - Thyroid hormones (T4 = thyroxine,
T3= triodo-thyronine) derived from
tyrosine - regulate metabolic rate,
growth, brain development.
Need to know enzymes and order
2. Protein & Polypeptide Hormones
- the major class of hormones.
- synthesized by proteolytic cleavage of pre-prohormones on E.R.,
& resulting prohormones are then often further cleaved to
hormones during packaging into vesicles by Golgi apparaatus.
- hormones (& pro-hormones, & “pro-fragments”) are released
by Ca2+-initiated exocytosis.
Portal system
Hypothalamus -Pituitary Complex:
- “master endocrine gland(s)”
- “neuro-endocrine interface”
PVN
Release of neurohormones
Bio 2A03
Lecture 31
Hormones II
Hypothalamus -Pituitary Complex:
- “master endocrine gland(s)”
- “neuro-endocrine interface”
PVN
Release of neurohormones
Posterior Pituitary Hormones
-”octapeptides” (8 a.a.’s peptides) synthesized in soma of giant
neurons of the hypothalamus.
-slowly transported down the giant axons by axonal transport &
stored like neurotransmitter in synaptic vesicles in terminal
knobs on blood vessels in post. pituitary.
- released by A.P’s coming down giant axons
1. Antidiuretic Hormone = ADH = Vasopressin
- from giant neurons of supra-optic nucleus (5/6 with 1/6 from PVN.)
- released as a response to low blood volume, low blood pressure,
high ECF osmotic pressure (hypothylamic osmoreceptors).
- promotes water retention at kindey and raises blood pressure by
vasocontricting systemic arterioles.
2. Oxytocin
- from giant neurons of paraventricular nucleus
- reproductive functions – uterine contractions, milk ejection,
orgasm (?)
Anterior Pituitary
Hypophysiotropic hormone
Hypothalamus- pituitary
portal system
Anterior pituitary
hormone
Hypothalamic & Anterior Pituitary Hormones
At least 6 different (probably
more) Hypophysiotropic hormones
= Releasing Hormones (factors) +
Inhibiting Hormones (factors),
from 6 different giant neuron
groups
-
-
-
+
T3, T4 ↑
Short loop –ve
CRH feedback
prevents the
buildup of excess
anterior pituitary
tropic hormone
ACTH
Fig 6-6
Biol 2A03
Lecture 32
Muscle 1
Skeletal Muscle
- Connected to at least 2
bones
- Some exceptions: some facial
muscles, larynx, external
urethral sphincter
Smooth Muscle
- No striations
- Found in blood vessels, GI
tract, uterus
Cardiac Muscle
- Show characteristics of
both skeletal & smooth
muscles
Comparison of skeletal, smooth and cardiac muscle
Structure of a skeletal muscle fiber (cell)
Muscles made up of bundles (fascicles) of muscle fibers
Neuromuscular junction
Each fiber (cell)
controlled by only 1
motor neuron
Multinucleated cells
Myofibrils
Mitochondria
SS – subsarcolemmal
IM - intramyofibril
sarcomere
The Sarcomere A band. Entire myosin bundle + overlapping
regions of actin.
I band. Regions of actin filaments which do not
Classic features overlap myosin. Bisected by Z line.
of sarcomeres
H zone. Area of sarcomere between opposing
ends of actin filaments.
Coupled to SR
Ca2+ channels
Excitation-contraction coupling
1. Action potential targets
charged amino acid residues
in DHP.
DHP = dihydropyridine
receptors.
Recruitment of motor units
Motor unit: motor neuron
5 fibers
and all the fibers that it
innervates
1. Motor units
7 fibers
2. A muscle can have
hundreds of motor units.
The size principle units are
recruited for small muscle
forces. units are
used for larger forces
Lecture 33
Muscle II
The Last One!
Recruitment of motor units
Motor unit: motor neuron
5 fibers
and all the fibers it
innervates
7 fibers
2. A muscle can have
hundreds of motor units.
Muscle tension can be
varied greatly
The size principle Small motor units are
recruited for small muscle
forces. Larger motor units are
used for larger forces
Muscles with low mitochondria are well suited for short bursts of energy use
Eg. In sprinters. Muscles with high mito levels are well suited for long-term endurance
Eg. In marathon runners. The two cannot be converted…but high mito can be trained
To work over shorter distances…low mito cannot be trained for endurance as easily
Smooth Muscle