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SIMPLE CONTENTS
NEWS & UPDATES
(Krebs LIR
Neuroscience 2017 Contents) V2 PDF
MAPS
OVERVIEW
CELLULAR
MUSCULOSKELETAL
MEANS
OF HOMEOSTASIS
CARDIOVASCULAR
RESPIRATORY
RENAL
GASTROINTESTINAL
ACHIEVEMENT
OF HOMEOSTASIS
METABOLISM
LIVER
NUTRITION
ENDOCRINE
REPRODUCTIVE
ACID BASE BALANCE
SODIUM
& WATER BALANCE,
FLUID COMPARTIMENTS
NEUROSCIENCE
- NEURO-PSYCHO-PHYSIOLOGY
FROM
ANIMAL MODEL TO HUMAN SOFTWARES
NORMAL
VALUES & CONSTANTS
- EQUATIONS
REFERENCES
TOC
DETAILED
CONTENTS
NEWS & UPDATES
MAPS
OVERVIEW
CELLULAR
& MOLECULAR
- VOLUME & COMPOSITION OF BODY FLUIDS
CELL MEMBRANES
TRANSPORT ACROSS
CELL MEMBRANES - DIFFUSION
- OSMOSIS
- ACTIVE
EPITHELIAL
& CONNECTIVE TISSUE - MOVEMENT ACROSS EPITHELIA
RESTING MEMBRANE POTENTIALS, ACTION POTENTIALS,
& NERVE TRANSMISSION - DIFFUSION POTENTIALS &
EQUILIBRIUM POTENTIALS
SYNAPTIC
& NEUROMUSCULAR TRANSMISSION - JUNCTION -
MUSCLE - CONTRACTION & RELAXATION
- METABOLISM
SKELETAL MUSCLE
SMOOTH MUSCLE
CARDIAC MUSCLE
BONE
SKIN
BLOOD
IMMUNE
- DEFENSE
CARDIOVASCULAR
RESPIRATORY
RENAL
GASTROINTESTINAL
/ NUTRITION - LIVER
-
NUTRITION
- HEPATIC & PANCREATIC
ENDOCRINE
/ REPRODUCTIVE - REPRODUCTION
-
METABOLISM
ACID
BASE BALANCE
SODIUM & WATER BALANCE,
FLUID COMPARTIMENTS
NEUROPSYCHOPHYSIOLOGY & NEUROSCIENCE
OVERVIEW
CELLS -
CELLULAR & MOLECULAR - BASIC NEUROPHYSIOLOGY
CENTRAL
PERIPHERAL
- NERVE - SENSORY RECEPTORS - EFFECTOR ENDINGS
AUTONOMIC /
VISCERAL
- PARASYMPATHETIC
- SYMPATHETIC - ENTERIC
SPINAL CORD,
BRAINSTEM & TRACTS - SENSORY & MOTOR
SENSORY
- SENSORY
RECEPTORS - SOMATO-SENSORY PATHWAYS
MOTOR - CONTROL OF MOVEMENT - MOTOR PATHWAYS
SPINAL CORD - SPINAL REFLEXES
BRAINSTEM SYSTEMS
& CRANIAL NERVES
BRAINSTEM & CRANIAL
NERVES
CONTROL OF EYE MOVEMENTS
- CN III OC - IV TRO - VI AB
- STRUCTURES INVOLVED - GAZE
SENSORY & MOTOR
INNERVATION OF THE HEAD & NECK
- CN V TRI - VII FA - IX GL - X VA - XI AC - XI HY
HEARING & BALANCE CN VIII VE - AUDITION & VESTIBULAR SYSTEM
BRAINSTEM SYSTEMS
RETICULAR FORMATION
BREATHING CENTER
HIGHER CORTICAL FUNCTION
CEREBRAL CORTEX
THALAMUS
VISION
MOTOR CONTROL SYSTEMS
BASAL GANGLIA
CEREBELLUM
INTEGRATION OF MOTOR CONTROL
MEMORY, EMOTION / MOTIVATION & HOMEOSTASIS
HYPOTHALAMUS
LIMBIC
OLFACTION / TASTE
PAIN
NORMAL VALUES & CONSTANTS
EQUATIONS
REFERENCES
TOC
MAPS
TOC
OVERVIEW
(Tellingen
2003 Contents) V1 JPG
(Costanzo
BRS 2018 Contents) V1 PDF
(Costanzo
BRS 2018 Contents) V2 PDF
(Costanzo
2013 Contents) V1 PDF
(Baillet
Physiologie 1992 Sommaire) V1 PDF
(Baillet 0
Prologue d'un ensemble de paradigmes a un plan constructif pour la
physiologie (modéliser le vivant) ) V1 JPG
HOMEOSTASIS
BLOOD
COMPOSITION
Blood sugar -
Osmoregulation - Blood pressure (Renin–angiotensin system) - Acid–base -
Fluid balance - Hemostasis - Proteostasis
OTHER
Predictive -
Thermoregulation
TOC
CELL
(Costanzo
BRS 2018) V1 PDF
(Ward Glance 2017 Cell) V1 PDF
(Ward
Glance 2017 Muscles)
V1
PDF
(Baillet 1
Membrane Cellulaire Sommaire) V1 JPG
(Baillet 2
Compartiment Sanguin Sommaire) V1 JPG
(Baillet 3
Communications
endocrines & paracrines Sommaire) V1 JPG
(Baillet
4
Homéostasie mitotique Sommaire)
V1
JPG
(Baillet 5
Communications nerveuses Sommaire)
V1 JPG
(Baillet 6 Myocyte
strie squelettique et synapse neuromusculaire Sommaire)
V1 JPG
(Baillet 7 Synapses du
système nerveux végétatif Sommaire) V1 JPG
(Baillet 8
Myocytes lisses Sommaire) V1 JPG
(Baillet 9
Homéostasie Immunitaire Sommaire) V1 JPG
(Baillet 10 Peau Sommaire) V1 JPG
(Baillet 11
Organisme, système multicellulaire et multicompartimenté Sommaire) V1 JPG
(Baillet 12
Organisation du système nerveux végétatif Sommaire) V1 JPG
(Baillet 13
Microcirculation Sommaire) V1 JPG
(Baillet 14
Myocytes cardiaques Sommaire) V1 JPG
OVERVIEW
nuclei,
endoplasmic reticulum (ER), lysosomes, Golgi apparatuses, mitochondria
Cells:
basic structural and functional unit of body
VOLUME
& COMPOSITION OF BODY FLUIDS
DISTRIBUTION
OF WATER IN THE BODY FLUID COMPARTMENTS
total body water
ICF
ECF
Plasma
Interstitial fluid ultrafiltrate
COMPOSITION
OF BODY FLUID COMPARTMENTS
Units
for Measuring Solute Concentrations
amounts
concentrations
mole millimole
equivalent
osmole Osmolarity
pH
Electroneutrality
of Body Fluid Compartments
principle of
macroscopic electroneutrality
cations anions
Composition
of Intracellular Fluid & Extracellular Fluid
ICF
ECF
Osmolarity
Creation
of Concentration Differences Across Cell Membranes
Concentration
Differences Between Plasma and Interstitial Fluids
Gibbs-Donnan
equilibrium/Ratio
NUCLEUS
Nucleus: contains most of a cell’s DNA; complexed with histones as
chromatin
Roles of the nucleus: transcription, regulation of cell division
Nucleolus : housed within the nucleus; synthesizes ribosomal
RNA
CYTOPLASM
CYTOSOL
Composition of cytosol: differs markedly fromextracellular fluid in
terms of electrolytes and pH
MEMBRANE-ENCLOSED ORGANELLES
Rough ER : protein synthesis
Smooth ER : drug detoxification; lipid and carbohydrate
synthesis
Golgi apparatus : post-translational modification of proteins,
packaging
of substances for intracellular or extracellular delivery, maintenance
of plasma membrane
Lysosomes : important in endocytosis, phagocytosis, autophagy
Acidic pH of lysosomes: removes M6P tags from proteins delivered to
lysosomes from Golgi apparatus
Mitochondria : contain their own DNA encoding for
mitochondrial proteins and transfer RNA
Mitochondrial energy production: occurs through aerobic metabolism;
defective in LHON
Mitochondrial DNA : inherited maternally
CYTOSKELETON
provides structural support and flexibility to cell, aids in cell
motility and division
Microfilaments : myriad functions; composed of G actin
Microtubules : composed of tubulin; components of cilia and
flagella
Intermediate filaments : most abundant of cytoskeletal elements
Intermediate filaments : form desmosomes and hemidesmosomes; example:
spectrin
NON–MEMBRANE-ENCLOSED ORGANELLES
Microvilli : projections of plasma membrane which aug surface
area; present in small intestines and proximal tubule of nephron
Centrioles : composed of microtubules; present in centrosome;
spindle fibers separate chromosome pairs
Cilia : motile or nonmotile; defective in Kartagener syndrome
Kartagener syndrome: ciliary dysmotility, bronchiectasis, chronic
sinusitis, situs inversus
Flagella : important in cell locomotion; present on sperm
Ribosomes : complexes of RNA and protein, which catalyze
protein synthesis using messenger and transfer RNA
JUNCTIONS
BETWEEN CELLS
Function
of tight junctions:
prevent most movement between cells, maintain membrane polarity in
terms of protein distribution between apical and basolateral membranes
Gap junctions: connect the
cytoplasm of adjacent cells; important in cardiac muscle and skin
Desmosomes: cell-to-cell
spot adhesions present on lateral
membrane of cells, which help resist shearing forces in squamous
epithelium
Hemidesmosomes: serve to attach
a cell to the ECM; composed of
cell adhesion proteins such as integrin
TOC
CHARACTERISTICS OF CELL MEMBRANES - MEMBRANE
COMPOSITION
STRUCTURE
LIPID
BILAYER
hydrophilic
hydrophobic amphipathic lipid bilayer
Fat steroid
Lipid-soluble substances Water-soluble
substances
Phospholipids
: glycerol backbone, fatty acid tails
phosphatidylserine,
phosphatidylethanolamine, phosphatidylcholine,phosphatidylinositol, and
phosphatidylglycerol. Sphingomyelin
Cholesterol
Glycolipids
impermeable to most
hydrophilic substances, which require pores
or transporter systems to penetrate membrane
PROTEINS
fluid mosaic model
INTEGRAL
hydrophobic
interactions
transmembrane
proteins
ion
channels, transporters, & receptors
PERIPHERAL
: Intracellular subcortical
cytoskeleton
Extracellular glycophosphatidylinositol
([GPI]) GPI-anchored proteins
electrostatic
interactions
ankyrin
Fluid mosaic model:
describes ability of proteins to move
freely within lipid bilayer
MORPHOLOGY
In select cell
types, the plasma membrane is folded to augm surface area
TOC
TRANSPORT ACROSS CELL
MEMBRANES
OVERVIEW
Downhill
Uphill
SIMPLE
DIFFUSION
OSMOSIS
CARRIER-MEDIATED
TRANSPORT
facilitated diffusion
primary active transport
secondary active transport
VESICULAR
TRANSPORT
OTHER
TYPES OF TRANSPORT
DIFFUSION
if unfavorable
active transport
Simple -
Facilitated
SIMPLE
DIFFUSION - NOT CARRIER MEDIATED
OVERVIEW
Simple diffusion:
movement of substance down its
concentration gradient across
semipermeable membrane; no energy or transporter required
electrochemical
UNCHARGED
- FICK LAW - Diffusion
of Nonelectrolytes -
can be measured using the following equation
J =
PA(DeltaC)
permeability
coefficient membrane surface area diffusion coeffi cient, partition
coefficient, thickness
net
diffusion
flux
flow (J)
CONCENTRATION
GRADIENT (CA − CB)
PARTITION
COEFFICIENT (K)
DIFFUSION
COEFFICIENT (D)
THICKNESS OF THE
MEMBRANE (ΔX)
DISTANCE
SURFACE AREA (A)
alveoli villi
microvilli capillaries
permeability (P)
Factors
that increase permeability
↑ Oil/water
partition coefficient
↓ Radius (size) of
the solute - Small hydrophobic molecules have the highest permeability
↓ Membrane
thickness
CHARGED
- Diffusion of Electrolytes
ion
- diffusion potential
-electrochemical equilibrium
- electrochemical gradient
Diffusion of
charged
substances: may not
necessarily flow down
their concentration
gradient depending on
electrical potential across
membrane
Cations: tend to
diffuse
into cells
Anions: tend to
diffuse
out of cells
DIFFUSION
OF NONPOLAR AND POLAR SUBSTANCES
Nonpolar substances
such as gases easily diffuse across lipid bilaye
DIFFUSION
OF GASES
Vg = DeltaP X A X d
/ T
OSMOSIS
autonomic nervous
system (ANS) closely monitors total body water (TBW)
Osmosis: diffusion
of water from high to lower concentration across semipermeable
membrane
OSMOLARITY
Osmolarity = g × C
isosmotic
hypo hyper
OSMOLALITY
OSMOTIC PRESSURE
generated
by solute concentration gradient across semipermeable membrane, promotes
osmosis
flow of water
Calculating osmotic pressure (van’t Hoff’s law) equation
π
= g × C × RT
The osmotic pressure increases when the solute concentration increases
Colloid
osmotic pressure, or oncotic pressure
Reflection coefficient (σ)
σ
= 1.0 serum albumin and intracellular proteins
σ = 0 Urea
ineffective osmole
σ = a value between
0 and 1 isosmotic
hypo hyper
Calculating
effective osmotic pressure
CARRIER-MEDIATED
TRANSPORT - CARRIERS
3
TYPES
facilitated
diffusion
primary active transport
secondary active transport
CHARACTERISTICS
Stereospecificity of transport
proteins: recognize only a single isomer of a substance
Saturation
Transport kinetics transport maximum (Tm) (Vmax)
Transport maximum :
above this transport rate, the substance can no longer be transported
into cells
Competition
for carrier binding sites
PORE
Aquaporin
(AQP)
CHANNELS
Ion
channels channel opening selectivity filter
FACILITATED
DIFFUSION - TRANSPORT
CHARACTERISTICS
OF FACILITATED DIFFUSION
Facilitated
transport : occurs down electrochemical
gradient; requires carrier transport molecules
does not require
metabolic energy
passive
rapid
carrier mediated
EXAMPLE
OF FACILITATED DIFFUSION
D-glucose GLUT4
diabetes mellitus
insulin
(PRIMARY)
ACTIVE TRANSPORT
ATPases that move
or “pump”
CHARACTERISTICS
OF PRIMARY ACTIVE TRANSPORT
“Uphill” - against an electrochemical gradient
direct input
of metabolic energy
(ATP) active
carrier
mediated
Active
transport: transport against electrochemical gradient; energy provided
by ATP hydrolysis
Primary
active transport: transport of substance across membrane directly
coupled to ATP hydrolysis
EXAMPLES OF PRIMARY ACTIVE TRANSPORT
Na+-K+
ATPase (Na+-K+ Pump) exchanger
then
secondary active transport in
all cells
Na+
and K+ are transported against their electrochemical gradients
usual stoichiometry
is 3 Na+/2 K+
electrogenic
E1 state E2 state
transport cycle
Cardiac glycosides
ouabain digitalis
Ca2+
ATPase (Ca2+ Pump) -
in
muscle cells
cell (plasma)
membranes (PMCA) sarcoplasmic reticulum (SR) endoplasmic reticulum
(SERCA)
H+-K+
ATPase (H+-K+ Pump)
Omeprazole
SECONDARY
ACTIVE TRANSPORT
simultaneous
movement of two substances across the cell membrane indirectly
coupled to ATP hydrolysis
Secondary active
transport: diffusion of substance down its concentration gradient
drives the transport of other substance against its concentration
gradient
CHARACTERISTICS
OF SECONDARY ACTIVE TRANSPORT
coupled
Na+ gradient
Cotransport
symport
Cotransport: both
substances transported in same direction
same direction
Na+-glucose cotransport (SGLT) and Na+-amino acid cotransport
Na+-K+-2Cl− cotransport SGLT1
Countertransport
antiport, or
exchange
Countertransport: substances move in opposite directions electrogenic
EXAMPLE OF NA+–GLUCOSE COTRANSPORT
EXAMPLE OF NA+–CA2+ COUNTERTRANSPORT OR
EXCHANGE
VESICULAR TRANSPORT
ENDOCYTOSIS (MEMBRANE INVAGINATION)
Endocytosis : internalization of a membrane-bound vesicle containing
extracellular material
Pinocytosis : random
sampling of extracellular fluid
through endocytotic vesicles
Receptor-mediated endocytosis :
receptors located on clathrin-coated
pit
→
complex is internalized after ligand binding
Fusing of the internalized clathrin-coated vesicle with acidic
environment of early endosome →
recycling
of clathrin to cell membrane
Examples of substances
transported through receptor-mediated endocytosis: LDL, transferrin
PHAGOCYTOSIS (ENGULFING)
Phagocytosis: actin-mediated
process whereby membranous extensions engulf solid
particles and internalize them
Oxidative burst: critical for
degradation of phagosomal contents
Phagocytosis: part of innate immunity; carried out in neutrophils
and macrophages; defects result in diseases such as chronic
granulomatous disease
EXOCYTOSIS
Exocytosis: triggered by ↑ in intracellular calcium
OTHER
TYPES OF TRANSPORT
PARACELLULAR
Paracellular
transport: occurs across “leaky” tight
junctions; example: proximal convoluted tubule of nephron
TRANSCELLULAR
(TRANSCYTOSIS)
Transcellular
transport: facilitated by polarized nature of epithelial and endothelial
membranes
CONVECTION
Convection:
transport of substances by the movement
of a medium
INTER
- CELLULAR COMMUNICATION
gap
junctions
Hormones
Paracrines
Autocrine
INTRA - CELLULAR SIGNALING
ligand-gated
channels, G protein–coupled receptors (GPCRs), or enzyme- associated
receptors. intracellular receptors
CHANNELS
G
PROTEIN–COUPLED RECEPTORS
membrane-spanning
regions second messenger cyclic 3 5 -adenosine monophosphate (cAMP),
cyclic 3 5-guanosine monophosphate (cGMP), and inositol trisphosphate
(IP3)
G
proteins
cAMP
signaling pathway
adenylyl cyclase
protein kinase A
(PKA)
phosphodiesterase
IP3
signaling pathway: Galphaq
phospholipase C
(PLC)
diacylglycerol
(DAG)
phosphatidylinositol
4,5-bisphosphate (PIP2)
calmodulin (CaM)
protein kinase C
CATALYTIC
RECEPTORS
guanylyl cyclase
tyrosine kinases (TRKs)
Receptor
activation
Intracellular
signaling
INTRACELLULAR
RECEPTORS
hormone
response element
BODY
FLUID pH
Acids
Buffer systems
Acid handling
TOC
EPITHELIAL &
CONNECTIVE TISSUE
EPITHELIA - INTERCELLULAR CONNECTIIONS
Tight
junctions (zonula occludens) “leaky”
Gap junctions
coupling
between myocardial cells
Structure
Types
Apical specializations
Basolateral membrane
Tight junctions
Gap junctions
Other junctional structures
MOVEMENT ACROSS EPITHELIA
Transcellular transport
Water movement
Solvent drag
Transepithelial voltage effects
CONNECTIVE TISSUE
Types
Extracellular
matrix
TOC
DIFFUSION POTENTIALS & EQUILIBRIUM POTENTIALS -
MEMBRANE EXCITABILITY -
MEMBRANE
POTENTIALS, ACTION POTENTIALS, & NERVE TRANSMISSION
membrane potential,
or Vm
action potentials
ion channel
OVERVIEW
RESTING
MEMBRANE POTENTIAL (RMP)
ACTION
POTENTIALS AP
TRANSMISSION
OF ACTION POTENTIALS BETWEEN CELLS
CONDUCTION
VELOCITY
TYPES
OF NEUROTRANSMITTERS
ION
CHANNELS
integral proteins
SELECTIVE
ION
CHANNELS MAY BE OPEN OR CLOSED
THE
CONDUCTANCE OF A CHANNEL
permeability gates
sensors
Voltage-gated
channels
activation gate on
the nerve Na+ channel
inactivation gate
Second
messenger–gated channels
Ligand-gated
channels
nicotinic receptor
on the motor end plate
MEMBRANE
POTENTIALS
“ground.”
resting potential
diffusion
potentials
DIFFUSION
POTENTIALS semipermeable
diffusion potential
is caused by diffusion of ions
size of the
diffusion potential
sign of the
diffusion potential
very few ions
magnitude
EQUILIBRIUM
POTENTIALS
electrochemical
equilibrium
equilibrium potential for K
Example of Na+ Diffusion (Equilibrium) Potential
Na+
diffusion potential
electrochemical
equilibrium
Example of Cl− Diffusion
(Equilibrium)
Potential
Cl−
equilibrium potential
electrochemical
equilibrium
NERNST
EQUATION to calculate equilibrium potentials
at what potential
would the ion be at electrochemical equilibrium?
Approximate values
for equilibrium potentials in nerve and skeletal muscle
DRIVING
FORCE & CURRENT FLOW
IONIC
CURRENT
Ionic current (IX)
direction of ionic
current
magnitude of ionic
current
RESTING
MEMBRANE POTENTIAL - RMP
−70 to −80 mV cell
negative
chord conductance
equation
Goldman equation
The resting
membrane potential is established by diffusion potentials
Each permeable ion
attempts to drive the membrane potential toward its equilibrium
potential
At rest, the nerve
membrane is far more permeable to K+ than to Na+
The Na+–K+ pump
contributes only indirectly electrogenic
Extracellular
ion effects
hyperkalemia
hypokalemia
Transporter
contribution
electrogenic
OVERVIEW
RMP:
dependent on concentration difference and on permeant
ions across cell membrane as well as equilibrium
potential of ions
RMP
is a negative value in most cells
Negative RMP
“powers” cotransport processes and generation of action potentials
SELECTIVE
MEMBRANE PERMEABILITY & EQUILIBRIUM POTENTIAL
Selective
permeability of membranes: a dynamic property; just think of changes in
membrane permeability to various ions during an action potential
Equilibrium
potential:membrane potential at which there is no net diffusion of the
ion across the membrane - Nernst equation
No net K+ flux when
membrane potential is -90 mV
CALCULATING
RMP: THE GIBBS-DONNAN EQUATION
RMP: reflects
equilibrium potential of most permeable ions and those with highest
equilibrium potential
Contribution of K+ to RMP: most permeable ion -> makes largest
contribution to RMP
INTRACELLULAR FIXED ANIONS
Intracellular fixed anions:unable to diffuse out of cells; draw in
cations such as K+
NA+,K+-ATPASE (SODIUM) PUMP
maintains concentration gradient for Na+ and K+ across cell membrane
electrogenic by virtue of removing 3 Na+ ions for every 2 K+ ions that
enter the cell—that is, creates negative intracellular electrical
potential
ACTION
POTENTIALS - EXCITATION - APs
Receptor potential
Terminology
Membrane potential
changes
Currents
inward current
outward current
OVERVIEW
Action
potential: rapid alteration in membrane potential that occurs in
excitable tissues in response to various stimuli
GENERATION OF AN ACTION POTENTIAL IN SKELETAL MUSCLE CELLS
Threshold
value: membrane potential once reached at which fast, voltage-gated Na+
channels open
Hyperpolarization phase: slight delay in which Na+, K+-ATPase pump
reestablishes the original transmembrane Na+ and K+ gradients
PROPERTIES OF ACTION POTENTIALS
“All or
none” phenomenon : if threshold is reached, action potential is
generated; if threshold is not reached, no action potential is generated
aug "Stimulus intensity " > aug frequency of action potential
generation, although action potential amplitude will remain unchanged
Refractory periods: prevent tetany
Absolute refractory period: action potential cannot be generated
regardless of stimulus intensity; occurs during depolarization phase
Relative refractory period: only much larger than normal stimulus
intensity can generate an action potential; occurs during
repolarization phase
Action potentials travel along axon without decrease in signal strength
because of insulating protein myelin
Where myelin is absent (nodes of Ranvier), the action potential travels
by saltatory conduction
TRANSMISSION
OF ACTION POTENTIALS BETWEEN CELLS
Electrical transmission: action potentials transmitted from cell to
cell through gap junctions; occurs in cardiac and smooth muscle
Chemical transmission: primary form by which action potentials are
generated
Chemical transmission: neurotransmitter binds postsynaptic ligand-gated
receptor > depolarization > action potential
Action potential traveling to terminal bouton triggers Ca+ influx and
release of neurotransmitter into synaptic cleft
Binding of neurotransmitter to postsynaptic ligand-gated receptor >
EPSP or IPSP
If summation of EPSPs and IPSPs reaches threshold at axon hillock >
action potential generated
Synaptic neurotransmitters degraded by enzymes in synaptic cleft or
removed by endocytosis to prevent excessive postsynaptic stimulation
CONDUCTION VELOCITY
Conduction velocity: dependent on myelin and axon diameter
Unmyelinated axons: much slower conduction velocity because of absence
of nodes of Ranvier
dim Distance between nodes of Ranvier > dim conduction velocity
TERMINOLOGY
- DEFINITIONS
Depolarization
less negative
Hyperpolarization
more negative
Inward
current
depolarizes
Outward
current
hyperpolarizes
Threshold
potential
Overshoot
Undershoot,
or hyperpolarizing afterpotential
Refractory
period
CHARACTERISTICS
OF ACTION POTENTIALS - DEFINITIONS
Stereotypical
size & shape
Propagation
All-or-none
response
IONIC
BASIS OF THE ACTION POTENTIAL
RESTING
MEMBRANE POTENTIAL
high resting conductance to K+ or permeability is
high
Na+ conductance is low
UPSTROKE OF THE ACTION POTENTIAL
Depolarization causes rapid opening of the activation gates of the Na+
channels
activation
gates
inward
Na+ current
overshoot
Tetrodotoxin
lidocaine
REPOLARIZATION OF THE ACTION POTENTIAL
Depolarization
also closes the inactivation gates of the Na+ channels
Depolarization slowly opens K+ channels
and increases K+ conductance
Tetraethylammonium
(TEA)
outward
K+ current
HYPERPOLARIZING
AFTERPOTENTIAL (UNDERSHOOT)
THE
NERVE NA+ CHANNEL
Closed, but available
resting
membrane potential
Open
upstroke
Inactivated
REFRACTORY
PERIODS
Absolute
Refractory Period
Explanation
Relative
Refractory Period
Explanation
Accommodation
hyperkalemia muscle
weakness
PROPAGATION
OF ACTION POTENTIALS
local
currents
cable properties
time constant (τ)
membrane resistance
(Rm)
membrane
capacitance (Cm)
length constant (λ)
Conduction
Velocity is increased by
Changes
in Conduction Velocity
Increasing nerve
diameter ↑
fiber size
Myelination
increased membrane resistance decreased membrane capacitance increased
conduction velocity nodes of Ranvier saltatory conduction
ION
CHANNELS
Activation
closed state
open state
open probability
Selectivity
nonselective
Conductance
Inactivation
CHANNEL
STRUCTURE
CHANNEL
TYPES
Voltage
gated
Ligand
gated
Cys-loop
superfamily
Ionotropic
glutamate receptors
Adenosine
triphosphate receptors
Second
messenger gated
Sensory
channels
Transient
receptor-potential channels (TRPs)
TOC
SYNAPTIC &
NEUROMUSCULAR TRANSMISSION
synapse
TYPES
OF SYNAPSES
ELECTRICAL
SYNAPSES
gap junctions
CHEMICAL
SYNAPSES
An
action potential in the presynaptic cell
Ca2+
enters the presynaptic terminal, release of neurotransmitter
receptors
on the postsynaptic cell membrane
Inhibitory
neurotransmitters
excitatory
neurotransmitters
synaptic cleft
unidirectional synaptic delay
NEUROMUSCULAR
JUNCTION - EXAMPLE OF A CHEMICAL SYNAPSE
STRUCTURE
OF THE NEUROMUSCULAR JUNCTION (NMJ)
NMJ: composed of a
presynaptic motor neuron, synaptic cleft, and postsynaptic membrane;
synonymous with motor end plate
MECHANISM
OF NEUROMUSCULAR TRANSMISSION
AP triggers
exocytosis of ACh from presynaptic neuron by influx of Ca2+
Synaptic delay:
time required for ACh to diffuse across synaptic cleft and bind
postsynaptic nicotinic receptors
End-plate
potential: local postsynaptic membrane depolarization created by binding
of ACh to nicotinic receptors
If end-plate
potential reaches threshold > action potential generated
ACh nicotinic
receptor
Motor
Units
Motoneurons
Sequence
of Events
Synthesis
and storage of ACh in the presynaptic terminal
Choline
acetyltransferase
synaptic vesicles
Depolarization
of the presynaptic terminal and Ca2+ uptake
opens Ca2+ channels
Ca2+
uptake causes release of ACh into the synaptic cleft
Diffusion
of ACh to the postsynaptic membrane (muscle end plate) and binding of
ACh to nicotinic receptors
Na+ and K+ ion
channel
ligand-gated
channels
End
plate potential (EPP) in the postsynaptic membrane
miniature end plate
potential (MEPP)
The
EPP is not an action potential
Depolarization
of adjacent muscle membrane to threshold
Degradation
of ACh
acetylcholinesterase (AChE)
AChE inhibitors (neostigmine)
Hemicholinium
acetylcholine (ACh)
choline acetyltransferase quantal
motor end plate nicotinic receptors end plate potential (EPP)
Na+-choline cotransport
Agents
That Alter Neuromuscular Function
Botulinus toxin
Curare
D-Tubocurarine α-bungarotoxin
Disease—myasthenia
gravis
reduced number of
ACh receptors
Treatment with AChE
inhibitors (e.g., neostigmine)
SYNAPTIC
TRANSMISSION
TYPES
OF SYNAPTIC ARRANGEMENTS
One-to-one
synapses (such as those found at the neuromuscular junction)
One-to-many
synapses
Many-to-one
synapses (such as those found on spinal motoneurons)
SYNAPTIC
INPUT - EXCITATORY & INHIBITORY POSTSYNAPTIC POTENTIALS
Excitatory
Postsynaptic Potentials
(EPSPs)
depolarize
opening of channels that are permeable to Na+ and K+
Excitatory neurotransmitters
Inhibitory
Postsynaptic Potentials (IPSPs)
hyperpolarize
opening Cl− channels
Inhibitory
neurotransmitters (GABA) glycine
INTEGRATION
OF SYNAPTIC INFORMATION - SUMMATION AT SYNAPSES
Spatial
Summation
Temporal
Summation
Other
Phenomena That Alter Synaptic Activity
Facilitation,
augmentation, and post-tetanic potentiation
Long-term
potentiation
Synaptic fatigue
TYPES
OF NEUROTRANSMITTERS
ACETYLCHOLINE
nlcotinlc
ACh receptors
muscarinic ACh receptors
acetylcholinesterase
Pathophysiology
of cholinergic transmission: myasthenia gravis, Parkinson disease,
Alzheimer dementia
NOREPINEPHRINE, EPINEPHRINE, AND DOPAMINE Biogenic
amines -
catecholamines
Monoamines:
norepinephrine, serotonin, dopamine; degraded by MAO and COMT
NE
postganglionic sympathetic neurons α or β receptors reuptake (MAO)
(COMT) metabolites pheochromocytoma VMA 3-methoxy-4-hydroxymandelic
acid
Norepinephrine:
synthesized by sympathetic neurons, adrenal medulla, locus ceruleus
E
adrenal medulla
D
midbrain inhibits prolactin secretion
D1
receptors
D2 receptors
Parkinson disease
Schizophrenia
L-dopa
dopaminergic
neurons
Adrenergic neurons
normetanephrine
metanephrine
Dopaminergic
pathways: nigrostriatal, mesolimbic, tuberoinfundibular pathways
SEROTONIN
Biogenic
amine
brain stem
Serotonin:
although most is located in the enteric nervous system, serotonin is
best known for its role in depression and mood disorders
HISTAMINE Biogenic
amine
hypothalamus
mast cells
GLUTAMATE
most prevalent
excitatory neurotransmitter
ionotropic
receptors
NMDA AMPA
receptors kalnate receptors
metabotropic
receptors (mGluRs)
Glutamate : primary
stimulatory neurotransmitter of the central nervous system; excess
activity > seizures
GLYCINE
inhibitory
neurotransmitter
increase Cl−
conductance
Glycine: primary
inhibitory neurotransmitter of spinal cord; pathophysiology: tetanus
toxicity
AMINOBUTYRIC
ACID (GABA)
inhibitory
neurotransmitter
GABAA receptor
ionotropic
benzodiazepines and
barbiturates
GABAB receptor
metabotropic
GABA: primary
inhibitory neurotransmitter of the brain; pathophysiology: Huntington
disease
NITRIC
OXIDE
inhibitory
neurotransmitter
NO synthase
NEUROPEPTIDES
Neuromodulators
Neurohormones
neuropeptides
axonal transport
Neuropeptides: alter gene expression > longer duration of action
Cotransmission: release of multiple substances simultaneously from
presynaptic neuron, allowing for more complex communication between
neurons
PURINES
ATP
cotransmitter
neuromodulators
TOC
SKELETAL MUSCLE
excitation-contraction
coupling
OVERVIEW
CONTRACTION
MUSCLE
STRUCTURE & FILAMENTS
Skeletal muscle:
joins bone to bone; cells large diameter and multinucleated
Transverse (T)
tubules: interconnect sarcolemma membrane and sarcoplasmic reticulum
Sarcomeres:
functional unit of skeletal muscle; overlapping of myosin and actin
filaments; striated appearance
myofibrils SR
transverse tubules (T tubules)
thick and thin
filaments sarcomeres
Z line to Z line
THICK
FILAMENTS
A band
Myosin
heavy chains light chains “tail” two
“heads” regulatory light chain essential light chain
THIN
FILAMENTS
I bands
Actin
G-actin F-actin
rigor
Tropomyosin
Troponin
TnC Ca2+-binding
protein
TnI
inhibit
actin/myosin interaction
TnT
tethers
the troponin complex to tropomyosin
ARRANGEMENT
OF THICK & THIN FILAMENTS IN SARCOMERES
Sarcomeric structure
Z
disks
crossbridges striated
A bands
I bands
bare zone
M line
Cytoskeletal
Proteins - Structural proteins
Actinin
α-Actinin
Titin
Dystrophin
Nebulin
SKELETAL
MUSCLE
myofibril
sarcolemma muscle fiber tendon fiber insertion and origin
SARCOPLASM
myoglobin
TRANSVERSE
TUBULES & THE SARCOPLASMIC RETICULUM SR - MEMBRANE SYSTEMS
T
tubules
dihydropyridine receptor
SR
site of Ca2+ storage and release
terminal cisternae
Triad excitation–contraction coupling
Ca2+ ATPase (Ca2+
pump) (SERCA)
calsequestrin
ryanodine receptor
NEUROMUSCULAR JUNCTION NMJ
motor endplate acetylcholine (ACh) nicotinic ACh receptors
(nAChRs)
Nicotinic acetylcholine receptors
motor endplate potential
Sodium channels
Signal termination
CONTRACTION
- STEPS
IN - EXCITATION-CONTRACTION COUPLING - IN SKELETAL MUSCLE -
Motoneuron action potential to muscle contraction
OVERVIEW
Motoneuron action potential
Action
potentials - Triad Role
T tubules L-type
Ca2+ channels (dihydropyridine receptors) tetrads
Depolarization
of the T tubules
Ca2+ release
channels (ryanodine receptors)
RyRs
increase in intracellular Ca2+ concentration
Ca2+ binds to troponin C
conformational change in troponin
Cross-bridge cycling
Myosin
binding
no ATP is
bound (A) rigor
state
ATP then
binds to myosin (B)
Adenosine
triphosphate binding
Adenosine
triphosphate hydrolysis
Myosin is
displaced toward the plus end of actin
power
(force-generating) stroke (D)
Adenosine
diphosphate release
Relaxation
SR
Ca2+-ATPase (SERCA)
MECHANISM OF CONTRACTION : THE SLIDING-FILAMENT THEORY
Calcium-induced
Ca2+
release: action potential transmitted from sarcolemma to T tubules
→ Ca2+ release from sarcoplasmic reticulum
Binding of
Ca2+ to troponin →
conformational change in troponin →
tropomyosin displaced → myosin
binding to actin (cross-bridging)
Sliding of
filaments: dependent on repetitive cycles of cross-bridging, pivoting,
and detachment of actin and myosin
Cross-bridge
cycling shortens the sarcomeres, pulling the Z disks closer together,
and muscle contracts
Muscle
relaxation: energy-requiring process dependent on pumping Ca2+ back into
sarcoplasmic reticulum
Absence of
Ca2+ → ↓ binding to troponin →
tropomyosin resumes original conformation → no more actin-myosin binding
TYPES OF CONTRACTION
Strength
of contraction: depends on number of muscle fibers recruited
Tetanus:
high-frequency stimulation →
summation of muscle twitches → tetany
Isotonic
muscle contraction: constant force produced in setting of changing
muscle length
Isometric muscle contraction:
constant force produced in setting of unchanging
muscle length
REGULATION OF CONTRACTION
Motor unit:
a single α-motor neuron and all of the corresponding muscle fibers it
innervates
The smaller
the motor unit (i.e., the fewer muscle fibers supplied by a motor unit),
the more precise the control of the muscle
Creation of
muscle tension: determined by degree of actin-myosin myofilament overlap
Length-tension
relationship:
similar to the Frank Starling relationship in cardiac
physiology: the greater the length and corresponding actin- myosin
overlap (to a point), the greater the tension developed
TYPES OF SKELETAL MUSCLE FIBER
Fast-twitch
fibers: use glycogen and anaerobic
metabolism →
fatigue easily but good for explosive high-intensity activity of short
duration
Fast-twitch
fibers: very little myoglobin →
whitish in color
Slow-twitch
fibers: use aerobic metabolism
so do not fatigue easily; rich in myoglobin →
red appearance; common in
muscles controlling posture
MECHANISM
OF TETANUS
MECHANICS
isometric
contraction length is held constant preload no shortening
Isotonic
contractions load is held constant (afterload) shortening
LENGTH-TENSION
RELATIONSHIP isometric contractions
Passive
tension
Total
tension
Active
tension
Active tension is
proportional to the number of cross-bridges formed
FORCE-VELOCITY
RELATIONSHIP isotonic contractions
velocity of
shortening decreases as the afterload increases
speed of
cross-bridge cycling
Stimulation
frequency
Twitch responses
Summation
Tetanus
Recruitment
TYPES OF SKELETAL MUSCLE FIBERS
Slow twitch Type I
Fast
twitch Type II
Type
IIa
Type IIx
Skeletal muscle adaptations
Atrophy
Hypertrophy
Muscle proprioceptors
Muscle
stretch receptors
Golgi tendon organ
PARALYSIS
Agents that affect nicotinic acetylcholine receptors
Agonists:
Succinylcholine
Antagonists
alpha-Bungarotoxin
Agents that affect acetylcholinesterase activity
myasthenia
gravis
TOC
SMOOTH MUSCLE
OVERVIEW
myosin
actin
STRUCTURE
Smooth
muscle : typically arranged around hollow organs; contraction reduces
lumen diameter
Smooth
muscle cells: nonstriated in appearance because of lack of sarcomeres
Absence
of sarcomeres →
contraction not dependent on
length-tension relationship
CONTRACTILE UNITS
Thick filaments
heavy
chains
light chains
essential light chain regulatory
light chain MLC20
“sidepolar”
Thin filaments
Caldesmon
Ca2+- calmodulin (CaM)
Calponin
Assembly
dense
bodies (desmosomes)
ORGANIZATION
vimentin
and desmin
dense plaques
adherens junctions
MEMBRANE SYSTEMS
L-type
Ca2+ channels (dihydropyridine receptors)
Ca2+ release from the sarcoplasmic reticulum (SR) via ryanodine
receptors
Caveolae
Sarcoplasmic reticulum inositol
trisphosphate (IP3)
Calcium-induced
calcium-release channels
Inositol
trisphosphate–gated calcium channels
NEUROMUSCULAR JUNCTION
autonomic
nervous system (ANS)
sympathetic nervous
system, parasympathetic nervous system, and enteric nervous system
varicosities
TYPES
OF SMOOTH MUSCLE
UNITARY
(SINGLE-UNIT) SMOOTH MUSCLE - PHASIC
Visceral
smooth muscle: predominant type
of smooth muscle in body; functions as syncytium
Unstable
RMP of smooth muscle in intestinal tract: gives rise to slow waves and
spike potentials
Pacemakers
unitary
uterus,
gastrointestinal tract, ureter, and bladder
slow
waves
gap
junctions
Action potentials
MULTIUNIT SMOOTH
MUSCLE - TONIC
Multiunit
smooth muscle: much less abundant
than single-unit smooth muscle; does not function as syncytium;
regulated by the autonomic nervous system
iris,
ciliary muscle of the lens, and vas deferens
densely
innervated
VASCULAR SMOOTH
MUSCLE
MECHANISMS IN
CONTRACTION - STEPS IN - EXCITATION-CONTRACTION COUPLING - IN SMOOTH
MUSCLE
no
troponin
Slow
waves → spike
potentials → muscle
contraction
Sustained
contraction: involves Ca2+ binding to calmodulin and activating myosin
light-chain kinase
Smooth muscle
relaxation: requires active pumping of Ca2+ into sarcoplasmic reticulum
CALCIUM
SOURCE
Hormones
& neurotransmitters
Calcium
influx - Depolarization of the
cell membrane opens voltage-gated Ca2+ channels
receptor-operated
Ca2+ channels (ROCCs)
Calcium-induced
calcium release CICR
“Ca2+
sparks”
Inositol
trisphosphate
G
protein–coupled receptors (GPCRs)
(IP3)–gated
Ca2+ channels
pharmacomechanical
coupling
CONTRACTION
Intracellular
[Ca2+] increases
thick-filament
regulated
calmodulin
myosin
light chain kinase
phosphorylates
myosin light
chain
Ligand-gated
Ca2+ channels IP3-gated Ca2+ release channels
calponin and
caldesmon
RELAXATION
Calcium
renormalization
Store
refill
storeoperated Ca2°
channel (SOC)
Stim1
Orai
Dephosphorylation
LATCHBRIDGE
FORMATION
REGULATION
OF CONTRACTION
Smooth
muscle contraction: typically not under voluntary control but can be
affected by the autonomic nervous system
Rho-kinase
Protein
kinase C
Mechanisms
That Increase Intracellular Ca2+ Concentration in Smooth Muscle
Voltage-gated
Ca2+ channels
Ligand-gated Ca2+
channels
IP3-gated Ca2+
channels phospholipase C (PLC)
Ca2+-Independent
Changes in Smooth Muscle Contraction
(Ca2+-sensitization)
(Ca2+-desensitization)
MECHANICS
Contraction
rate
Length adaptation
Vascular smooth muscle contraction & relaxation
TOC
CARDIAC MUSCLE
STRUCTURE
Cardiomyocytes
: interconnected through gap junctions →
syncytium; sarcomeres cause striated appearance
Troponin
Communication
pathways
sinoatrial node
Pacemaker
Gap junctions
intercalated discs
desmosomes and fascia adherens
Cellular branching
syncytium
Transverse
tubules and sarcoplasmic reticulum
electromechanical transduction
Location
Diads
MECHANISMS
IN CONTRACTION
Cardiac
mechanism of contraction: sliding filament mechanism; extracellular
Ca2+ plays important role; contraction in “all or none” manner
REGULATION
OF CONTRACTION
RMP
potential of cardiac cells: unstable → pacemaker activity
Effects of SNS: +
chronotropy, + dromotropy, + inotropy, + lusitropy
Effects of PNS: -
chronotropy, - dromotropy, - inotropy
CONTRACTILITY
REGULATION
Calcium-induced
calcium release
dihydropyridine
receptors
ryanodine receptors
trigger flux
Ca2+-induced Ca2+ release (CICR)
Contractility
regulation
Sympathetic
activation
Calcium channels
Calcium pump
phospholamban
Relaxation
Calcium release
PRELOAD
DEPENDENCE
Cardiac
output
Frank-Starling law
of the heart
Length-dependent
activation
Preload
limits
ENERGY
SOURCE
myocardial
infarction
TOC
COMPARISON
OF SKELETAL MUSCLE, SMOOTH MUSCLE, & CARDIAC MUSCLE
TOC
BONE
OVERVIEW
FORMATION
ANATOMY AND GROWTH
REMODELING
REGULATION
Bone formation
Endochondral
ossification
Membranous ossification
Cell biology of bone
Osteoblast
Osteoclast
Parathyroid hormone
Estrogen
TOC
SKIN
CONTENTS
(Baillet 10 Peau ) V1 JPG
Skin
layers
Epithelial cell junctions
Exocrine glands
TOC
BLOOD
Hemoglobin electrophoresis
Coombs test
Platelet plug formation (primary
hemostasis)
Thrombogenesis
Coagulation and kinin pathways
Vitamin K–dependent coagulation
TOC
IMMUNE SYSTEM
(Baillet 9
Homéostasie Immunitaire) V1 PDF
CONTENTS
(Baillet 9
Homéostasie Immunitaire) V1 JPG
TOC
CARDIOVASCULAR
(Costanzo
BRS 2018) V1
PDF
(Ward
Glance 2017) V1 PDF
(Baillet 11
Organisme, système multicellulaire et multicompartimenté Sommaire) V1 JPG
(Baillet 12
Organisation du système nerveux végétatif Sommaire) V1 JPG
(Baillet 13
Microcirculation Sommaire) V1 JPG
(Baillet 14
Myocytes cardiaques Sommaire) V1 JPG
(Baillet
15
Pompe cardiaque Sommaire)
V1 JPG
(Baillet
16
Du
potentiel d'action a l'ecg : excitation de la pompe cardiaque Sommaire) V1 JPG
(Baillet
17
Secteurs
haute et basse pression Sommaire)
V1 JPG
(Baillet
18
Circulation
coronaire et métabolisme myocardique Sommaire)
V1 JPG
(Baillet
19
Homéostasie
circulatoire a court terme (pression artérielle) Sommaire)
V1 JPG
CONTENTS
HEART
CARDIAC
MECHANICS
CARDIAC
PERFORMANCE - CARDIAC OUTPUT =
HEART RATE X STROKE VOLUME. CAN ALSO BE CALCULATED WITH FICK PRINCIPLE,
PALPATING METHOD
Cardiac cycle - Afterload - Preload - Frank–Starling law - Cardiac
function curve -Venous return curve
Stroke volume (= end-diastolic volume − end-systolic volume)
Ejection fraction (= stroke volume / end-diastolic volume)
Cardiac output is mathematically to systole
Inotropic, chronotropic, and dromotropic states
Cardiac input (= heart rate x suction volume Can be calculated by
inverting terms in Fick principle)
Suction volume (= end-systolic volume + end-diastolic volume)
Injection fraction (= suction volume / end-systolic volume)
Cardiac input is mathematically to diastole
Frank–Starling law of the heart
Wiggers diagram
Pressure volume diagram
ULTRASOUND
Fractional shortening = (End-diastolic dimension End-systolic dimension)
/ End-diastolic dimension - Aortic valve area calculation - Ejection
fraction - Cardiac index - Left atrial volume
HEART RATE
Cardiac pacemaker - Chronotropic (Heart rate) - Dromotropic (Conduction
velocity) - Inotropic (Contractility) - Bathmotropic (Excitability) -
Lusitropic (Relaxation)
MYOCARDIAL
OXYGEN SUPPLY & DEMAND
PATHOPHYSIOLOGY
OF MYOCARDIAL ADAPTATIONS
ELECTROPHYSIOLOGY
OF THE HEART - ELECTRICAL
CONDUCTION SYSTEM OF THE HEART - CONDUCTION
Conduction
system
- Cardiac electrophysiology - Action potential cardiac atrial
ventricular - Effective refractory period - Pacemaker potential -
Electrocardiography P wave PR interval QRS complex QT interval ST
segmentT waveU wave - Hexaxial reference system
Electrocardiogram
Cardiac marker
Cardiac action potential
ELECTROCARDIOGRAM
CHAMBER
PRESSURE
Central venous - Right atrial ventricular pulmonary artery wedge - Left
atrial ventricular - Aortic
OTHER
Ventricular remodeling
VASCULAR
/ HEMODYNAMICS
BLOOD FLOW
Compliance - Vascular resistance - Pulse - Perfusion
BLOOD PRESSURE
Pulse pressure - Systolic - Diastolic - Mean arterial pressure -
Jugular venous pressure - Portal venous pressure - Critical closing
pressure
ARTERIAL
PRESSURE MAINTENANCE - REGULATION
OF BLOOD PRESSURE
Baroreflex - Kinin–kallikrein system - Renin–angiotensin system -
Vasoconstrictors - Vasodilators - Autoregulation - Myogenic
mechanism - Tubuloglomerular feedback - Cerebral autoregulation -
Paraganglia - Aortic body - Carotid body - Glomus cell
Baroreceptor
Baroreflex
Renin–angiotensin system
Renin
Angiotensin
Juxtaglomerular apparatus
Aortic body and carotid body
Autoregulation
Cerebral Autoregulation
HEMODYNAMICS
Under most circumstances, the body
attempts to maintain a steady mean arterial pressure
When there is a major and immediate
decrease (such as that due to hemorrhage or standing up), the body can
increase the following
Heart rate
Total peripheral resistance (primarily due to vasoconstriction of
arteries)
Inotropic state
In turn, this can have a significant
impact upon several other variables
Stroke volume
Cardiac output
Pressure :
Pulse pressure (systolic pressure - diastolic pressure)
Mean arterial pressure (usually approximated with diastolic pressure + 1/3
pulse pressure)
Central venous pressure
FLUID
EXCHANGE IN THE CAPILLARIES
PATHOPHYSIOLOGY
OF HEART FAILURE
CIRCULATORY
INSUFFICIENCY
REGIONAL CIRCULATION
END OF CONTENTS
CARDIAC
MECHANICS
CARDIAC CYCLE : COMPOSED OF SYSTOLE & DIASTOLE
Systole
Diastole
Pulse
pressure: ↑ in hyperthyroidism, aortic regurgitation; ↓ in aortic
stenosis
HEART VALVES - Function to establish one-way flow of blood in the heart
Atrioventricular valves: mitral and tricuspid valves
Atrioventricular
valves: prevent backflow of blood into atria during systole
Semilunar valves: aortic and pulmonic valves
Semilunar
valves: prevent backflow of blood into ventricles during diastole
PRINCIPAL HEART SOUNDS - Reflect valve closure and/or pathologic states
S1: closure of AV valves
S1: closure
of AV valves; typically auscultated as a single sound
S2: closure of semilunar valves
S2: normally
“split” during inspiration
S2: best
appreciated in the 2nd or 3rd left intercostal space
S3: ventricular gallop
S3: presence
reflects volume-overloaded state
S4: atrial gallop
S4: atrial
contraction against a stiff ventricle, often heard after an acute
myocardial infarction
VENTRICULAR PRESSURE CHANGES DURING THE CARDIAC CYCLE
S1:
due to closure of AV valves in early
systole from ↑ ventricular pressure
S2: due to closure of semilunar valves in early
diastole because pulmonic/aortic pressures exceed
intraventricular pressures
CARDIAC
PERFORMANCE assessed by
measuring cardiac output
CARDIAC
OUTPUT
CO = HR X SV
oxygen consumption
CO = O2
consumption / A - V O2 gradient
STROKE
VOLUME
Stroke
volume (SV)
Stroke volume = EDV
- ESV
Ejection
fraction EF
Ejection
fraction = SV/EDV
Determinants
of stroke volume
Stroke volume:
dependent on preload, contractility, and afterload
Preload: “load”
placed on ventricle at start of systole; equivalent to EDV
Frank-Starling
relationship: increased preload (to a point) results in increased CO
Increased preload →
↑ stretching of sarcomeres → ↑ sensitivity to Ca2+
Contractility: ↑
with digitalis, sympathetic stimulation ; ↓ in heart failure
Afterload: ↑
in aortic stenosis and hypertension, ↓
with intra- aortic balloon pump
Mechanical
characterization of contraction
Laplace
relationship: myocardial wall tension needs to ↑
in
order to generate an ↑
intraventricular pressure to overcome an ↑
afterload
Left
ventricular hypertrophy: occurs by addition of sarcomeres in parallel
Stroke work:
↑ with
increasing SV or by maintaining constant SV in face of ↑ afterload
Pressure-volume
component of stroke work: work used to push SV into high-pressure
arterial system (major component)
Kinetic-energy
component of stroke work: work used to move ejected SV at a certain
velocity (minor component)
VENOUS
RETURN VR
Effect
of venous return on cardiac output by influencing preload
Venous return: rate
determined by pressure gradient between systemic veins and right atrium
Venous return is
decreased at increased right atrial pressures
Venoconstriction or
intravenous volume infusion → ↑ systemic venous pressure → ↑ venous return and CO
Venodilation or loss of blood → ↓
systemic venous pressure → ↓
venous return and CO
On average, CO
and venous return need to be perfectly matched to ensure adequate CO
and arterial perfusion and prevention of venous congestion
Other
determinants of venous return
Respiratory pump: ↑ VR during
inspiration due to ↓
intrathoracic and ↑
abdominal pressures
VENTRICULAR
PRESSURE-VOLUME LOOPS
Phase I:
ventricular filling in diastole after opening of mitral valve
Phase II:
isovolumic ventricular contraction after closing of mitral valve
Phase III: ejection
of blood after opening of aortic valve
Phase IV:
isovolumic ventricular contraction after closing of aortic valve
ATRIAL
PRESSURE CHANGES DURING THE CARDIAC CYCLE
a wave: atrial
contraction →
slight ↑ in atrial
pressure
c wave: isovolumic ventricular contraction and inward bulging of AV valves
→ large ↑ in atrial pressure
x descent: start of ventricular ejection →
rapid ↓ in atrial
pressure
v wave: atrial filling after closure of AV valves →
gradual ↑ in
atrial pressure
PATHOPHYSIOLOGY
OF THE MAJOR VALVULAR DISEASES
Aortic
stenosis
Aortic
stenosis: ↑
afterload, ↓ stroke
volume, pulsus parvus et tardus
Aortic
regurgitation (insufficiency)
Aortic
regurgitation: ↓
effective SV, widened pulse pressure
Aortic
regurgitation: increased SV and decreased diastolic pressure → Water Hammer pulse on
exam
Mitral stenosis
Mitral
stenosis: rheumatic
fever still most common
cause
Mitral stenosis: associated with large diastolic pressure difference between
left
atrium and ventricle
Mitral stenosis: ↑ left
atrial pressures → ↑ hydrostatic pressures
in
pulmonary circulation → pulmonary edema
Symptoms of
pulmonary
edema: dyspnea, reduced
exercise capacity
Treatment of severe symptomatic mitral stenosis: mitral valve repair
(commissurotomy),
balloon valvuloplasty, or
valve replacement
Mitral
regurgitation (insufficiency)
Mitral
regurgitation: mitral valve does not form good seal → blood
flows into left atrium during early systole
Precise
symptoms of mitral regurgitation depend on temporal course of the mitral
regurgitation; acute onset →
severe symptoms; chronic onset →
typically asymptomatic or minor symptoms
Pathophysiology
of murmurs
Murmurs:
most likely with high-flow velocity in large vessels
MYOCARDIAL
OXYGEN SUPPLY & DEMAND
MAIN
DETERMINANTS OF MYOCARDIAL O2 SUPPLY
Coronary blood flow
Coronary
blood flow: dependent on length of diastole, diastolic perfusion
pressure, coronary vascular resistance
Left ventricular
myocardial perfusion largely occurs during diastole
Diastolic
perfusion
pressure: driving force for coronary artery perfusion; equal
to diastolic pressure in proximal aorta; augmented with use of
intra-aortic balloon pump
Coronary
blood flow: left
ventricular myocardial
perfusion largely occurs
during diastole
Vascular
resistance: ↑
by
atherosclerotic narrowing
of coronary vessels
Local vasodilatory substances: adenosine, hydrogen ions, and potassium
Arterial O2 content
O2-carrying
capacity
of blood dependent on hemoglobin concentration and efficiency
of oxygen exchange across the pulmonary membrane
Severe anemia
compromises myocardial O2 supply
DETERMINANTS OF
MYOCARDIAL O2 DEMAND
Heart rate
Determinants
of myocardial O2 demand: heart rate most important
Myocardial wall
tension
Increased
preload, contractility, or afterload → ↑ wall tension → ↑
O2 demand
Contractility
PATHOPHYSIOLOGY OF
ANGINA PECTORIS
Angina
pectoris: occurs when myocardial O2 demand exceeds O2 supply
Coronary artery
spasm can cause Prinzmetal angina; difficult to diagnose
PATHOPHYSIOLOGY
OF MYOCARDIAL ADAPTATIONS
ADAPTATIONS TO INCREASED AFTERLOAD
Concentric
hypertrophy → stiff ventricle →
predisposes to diastolic congestive heart failure
Concentric hypertrophy: sarcomeres added in parallel →↓ wall
tension
ADAPTATIONS TO INCREASED PRELOAD
Eccentric
hypertrophy: occurs in “volume- overloaded” hearts
Eccentric hypertrophy: sarcomeres are added in series to elongate the
ventricle and increase ventricular lumen volume
ELECTROPHYSIOLOGY
OF THE HEART
OVERVIEW
Backup nodes
will “fire” if the SA node fails to generate an action potential
ELECTROPHYSIOLOGIC BASIS OF SPONTANEOUS DEPOLARIZATION OF SA NODE &
OTHER BACKUP NODES
RMP of nodal
tissues constantly depolarizing because of Na+ leak
Phase 4:
membrane Na+ permeability → continuous
depolarization
Phase 0:
when threshold potential is reached Ca2+ channels open, generating an
action potential
Phase 3:
Ca2+ channels close, K+ effluxes, and membrane potential is restored
AUTONOMIC INFLUENCE ON HEART RATE
PNS ↓ maximum
diastolic potential → slower heart rate
Slope of phase 4 depolarization: ↑ by SNS, ↓
by PNS
Threshold for AP generation: ↑ by SNS,
↓
by PNS
BACKUP PACEMAKERS
Overdrive
suppression: mechanism by which SA node prevents backup pacemakers from
initiating an AP
CONDUCTION PATHWAY OF ACTION POTENTIALS
ACTION POTENTIALS IN CARDIAC MUSCLE
Phases in cardiac myocytes
RMP in
contractile cardiomyocytes: approximately -90 mV
Depolarization:
opening of fast, voltage-gated Na+ channels
Calcium
plateau: balance between K+ efflux and Ca2+ influx
Repolarization:
simultaneous rapid efflux of K+ and cessation of Ca2+ influx
Differences in action potential generation in nodal cells & myocytes
RMP in nodal
cells: approximately -70 mV
Refractory period
Refractory
period: prevents tetany (sustained systole) and places upper limit on
heart rate
EXCITATION-CONTRACTION COUPLING
Excitation-contraction
coupling: “coupling” of ↑ in
membrane potential (excitation) to cell contraction
Force of
cardiomyocyte contraction proportional to intracellular [Ca2+]
Ventricular
relaxation: energy requiring process where Ca2+ is pumped into the
sarcoplasmic reticulum and extracellular fluid
Sympathetic
excitation: + inotropic effect by ↑ influx of
extracellular Ca2+
AUTONOMIC INNERVATION OF THE HEART
Sympathetic (adrenergic) innervation
Sympathetic
innervation of the heart: innervates both atria and ventricles;
parasympathetic innervation is only to the atria
Parasympathetic (cholinergic) innervation
Parasympathetic
nervous system: does not innervate the ventricles; allows for
ventricular escape rhythm to be generated following some forms of
syncope
ELECTROCARDIOGRAM
(ECG)
OVERVIEW
ECGs monitor
electrical activity in heart by recording electrical changes at the body
surface
THE NORMAL ECG
Bipolar
leads (I, II, and III) and unipolar leads (aVR, aVL, and aVF) detect
current in the vertical (frontal) plane
Precordial leads (V1 through V6) detect current in the transverse plane
P wave: atrial depolarization
PR interval: time spent during conduction through AV node
QRS complex: ventricular depolarization
T wave: ventricular repolarization
DETERMINATION OF AXIS
CORRELATION OF ECG WITH CARDIAC EVENTS
ABNORMAL ECGS
Atrial
fibrillation: no P waves, irregular ventricular response
Atrial flutter: sawtooth F (flutter) waves
First-Degree AV block: PR interval uniformly prolonged > 0.2 second
Mobitz type 1 second- degree AV block: PR interval lengthens
progressively until P wave is “dropped”
Second-degree heart block (Mobitz type 2): not all P waves are
conducted, so some P waves will not give rise to a QRS complex
Third-degree AV block: no relationship between P waves and QRS complex
Ventricular tachycardia: often a precursor to potentially fatal
ventricular fibrillation
Wolff-Parkinson-White syndrome: note the presence of the delta wave
ARTERIAL
PRESSURE MAINTENANCE
DETERMINANTS OF MEAN ARTERIAL PRESSURE (MAP)
MAP = CO x
TPR
Poiseuille
relationship : R = 8ηl/πr4
Resistance to fluid flow in a vessel is inversely related to the 4th
power of the radius
Resistance
in circulatory system: determined primarily by diameter of arterioles
rather than large arteries
Medullary
vasomotor center: tonic sympathetic outflow that maintains vasomotor
tone and TPR
RAPID BLOOD PRESSURE CONTROL BY THE AUTONOMIC NERVOUS SYSTEM
Baroreceptor
reflex: dependent on mechanoreceptors in aortic arch and carotid sinuses
CNS ischemic
response: may be seen in stroke to ↑ cerebral perfusion
AUTOREGULATION OF LOCAL BLOOD FLOW
Metabolic
mechanism: demand regulates supply by production of vasodilatory
substance
Myogenic mechanism: VSMC contraction dependent on Ca2+ permeability
VASCULAR COMPLIANCE
Arteriosclerosis:
arteries become noncompliant and contribute to development of
hypertension
Compliant
vessel: able to withstand ↑ in
volume without causing significant ↑ in
pressure
Veins are
much more compliant than arteries
LONG-TERM CONTROL THROUGH REGULATION OF INTRAVASCULAR VOLUME BY THE
KIDNEYS
Kidneys control blood
pressure by regulating intravascular volume
Pressure
diuresis: ↑ BP → ↑ GFR
→
↑
Na+/H2O excretion → ↓
intravascular volume → ↓ BP
RAAS:
activated by renal hypoperfusion
Angiotensin
II: stimulates renal Na+ reabsorption, thirst, and systemic
vasoconstriction
Actions of
aldosterone: stimulates renal Na+ reabsorption and K secretion; ↑
intravascular volume and MAP
Pathology of excess aldosterone: hypokalemic metabolic alkalosis and
difficult to treat hypertension
ADH
secretion: More sensitive to ↑ plasma osmolarity than
↓
plasma volume
Low-pressure
stretch receptors response to ↑ venous
return: ↑ renal
perfusion, ↑ HR
(Bainbridge reflex), ↑ ANP
secretion, ↑ diuresis
ANP: atrial stretching ↑
secretion → promotes diuresis
BNP: ventricular stretching ↑
secretion → promotes diuresis
FLUID
EXCHANGE IN THE CAPILLARIES - CAPILLARY FLUID EXCHANGE
-
ENDOTHELIAL
EXCHANGE PROCESSES
OVERVIEW
STARLING FORCES
HYDROSTATIC PRESSURE OF THE CAPILLARY (Pc)
↓
Capillary hydrostatic pressures: hemorrhage, hypotension,
hypoalbuminemia
↑ Capillary
hydrostatic pressure forces fluid into the interstitium, causing edema
PLASMA ONCOTIC PRESSURE OR PLASMA COLLOID OSMOTIC PRESSURE (Πc)
Plasma
oncotic pressure: keeps fluid in the vascular compartment
↓ Plasma
oncotic pressure leads to fluid accumulation in the interstitium (edema)
INTERSTITIAL HYDROSTATIC PRESSURE (PIF)
Interstitial
hydrostatic pressure: slightly negative because of constant drainage by
the lymphatics
INTERSTITIAL ONCOTIC PRESSURE (PIF)
Interstitial
oncotic pressure: outward force (typically small) exerted by
interstitial proteins
STARLING EQUATION
Small NFP
able to drive capillary filtration due to high permeability of capillary
membrane
PATHOPHYSIOLOGY OF EDEMA
Lymphatic
system: returns excess fluid to the vascular compartment through the
thoracic duct
Dysfunction of lymphatic system → edema
Edema: excess fluid (transudate, exudate, lymphatic, glycosaminoglycans)
in interstitium
PATHOPHYSIOLOGY
OF HEART FAILURE
DEFINITION
SYSTOLIC HEART FAILURE: “PUMP” FAILURE
Systolic
heart failure: pump failure (impaired contractility, increased
afterload)
DIASTOLIC HEART FAILURE
Diastolic
heart failure: impaired ventricular filling during diastole due to
stiff ventricle or obstruction to ventricular filling (e.g., mitral
stenosis)
Examples of
obstruction to left ventricular filling: mitral stenosis, cardiac
tamponade
HIGH-OUTPUT HEART FAILURE
High-output
heart failure: usually precipitated by peripheral conditions in which
the body requires a pathologically elevated CO
COMPENSATORY MECHANISMS IN HEART FAILURE
Compensatory
responses in heart failure: Frank- Starling relationship, myocardial
hypertrophy, neurohormonal activation
CIRCULATORY
INSUFFICIENCY
SIGNS AND SYMPTOMS
Shock: cold
and clammy skin, rapid and weak pulse, confusion, and reduced urinary
output
PATHOPHYSIOLOGIC BASIS FOR CLASSIFICATION OF SHOCK
Types of
shock: cardiogenic, distributive, hypovolemic
Cardiogenic shock: “pump” failure
Distributive
shock: vasodilation →
↓
peripheral resistance →
hypotension →
tissue ischemia
UNSORTED
OVERVIEW
BLOOD VESSELS & BLOOD FLOW
CARDIAC IMPULSE GENERATION AND CONDUCTION
EXCITATION IN ELECTROLYTE DISTURBANCES
CARDIAC ARRHYTHMIAS
VENTRICULAR PRESSURE-VOLUME RELATIONSHIPS
CARDIAC WORK AND CARDIAC POWER
REGULATION OF STROKE VOLUME
VENOUS RETURN
ARTERIAL BLOOD PRESSURE
MYOCARDIAL OXYGEN SUPPLY
REGULATION OF THE CIRCULATION
CIRCULATORY SHOCK
FETAL & NEONATAL CIRCULATION
BLOOD
PRESSURE
CIRCULATION
HEART
VASCULATURE
CARDIAC OUTPUT VARIABLES
Stroke volume
Contractility
Preload
Afterload
Myocardial oxygen demand
CARDIAC OUTPUT EQUATIONS
Stroke volume
Ejection fraction
Cardiac output
Pulse pressure
Mean arterial pressure
STARLING CURVES
RESISTANCE, PRESSURE, FLOW
CARDIAC AND VASCULAR FUNCTION CURVES
Inotropy
Venous return
Total peripheral resistance
PRESSURE-VOLUME LOOPS & CARDIAC CYCLE
PRESSURE-VOLUME LOOPS & VALVULAR
DISEASE
Aortic stenosis
Mitral regurgitation
Aortic regurgitation
Mitral stenosis
SPLITTING OF S2
Physiologic splitting
Wide splitting
Fixed splitting
Paradoxical splitting
AUSCULTATION OF THE HEART
Standing, Valsalva (strain phase)
Passive leg raise
Squatting
Hand grip
Inspiration
HEART MURMURS
Systolic
Aortic stenosis
Mitral/tricuspid regurgitation
Mitral valve prolapse
Ventricular septal defect
Diastolic
Aortic regurgitation
Mitral stenosis
Continuous
Patent ductus arteriosus
MYOCARDIAL ACTION POTENTIAL
PACEMAKER ACTION POTENTIAL
TORSADES DE POINTES
Congenital long QT syndrome
BRUGADA SYNDROME
WOLFF-PARKINSON-WHITE SYNDROME
ECG TRACINGS
ATRIAL NATRIURETIC PEPTIDE
B-TYPE (BRAIN) NATRIURETIC PEPTIDE
BARORECEPTORS & CHEMORECEPTORS
NORMAL CARDIAC PRESSURES
AUTOREGULATION
CARDIAC ELECTROPHYSIOLOGY
conducting and contractile cells
RESTING MEMBRANE POTENTIAL
equilibrium (or Nernst) potential (EK)
CARDIAC ACTION POTENTIALS
Fast-Response (Ventricular) Action Potential
Slow-Response (Pacemaker) Action Potential
Cardiac Pacemakers
automaticity
native pacemakers overdrive suppress latent pacemakers
Conduction Velocity
Refractory Period
closure of Na+ channel inactivation gates
Absolute
Effective
Relative
CARDIAC MUSCLE & CONTRACTION
EXCITATION-CONTRACTION COUPLING
L-type Ca+ channels
Ca2+-induced Ca2+ release
Myocardial Contraction and Relaxation
Influx of extracellular Ca2+ into myocardial cells L-type Ca2+
Ca2+-induced Ca2+ release ryanodine receptors
Myocardial contraction troponin C tropomyosin
Myocardial relaxation
CARDIAC OUTPUT
afterload, preload, and contractility
FICK’S CARDIAC OUTPUT
STROKE VOLUME
EJECTION FRACTION
DETERMINANTS OF CARDIAC OUTPUT
Afterload
wall stress (σ)
increases
decreases
Preload
Length-Tension Relationship & Contractility (Inotropy)
lengthtension
relationship preload
Contractility independent ejection fraction
Frank-Starling Relationship
length-tension relationship preload (LVEDV or LVEDP) (CO or SV)
positive inotropic agents
negative inotropic agents
PRESSURE-VOLUME LOOPS
compliance curve
1 → 2: ISOVOLUMETRIC CONTRACTION (SYSTOLE)
2 → 3: VENTRICULAR EJECTION (SYSTOLE)
3 → 4: ISOVOLUMETRIC RELAXATION (DIASTOLE)
4 → 1: VENTRICULAR FILLING (DIASTOLE)
Rapid filling
slow filling
VARIABLES THAT AFFECT PV LOOPS
CARDIAC & VASCULAR FUNCTION CURVES
Cardiac function curve
Vascular function curve
Steady-state CO and venous return
Mean systemic pressure x-intercept of the vascular function curve
Systemic vascular resistance (SVR)
THE CARDIAC CYCLE
PRESSURE TRACINGS DURING THE CARDIAC CYCLE
Pressure Changes in Diastole and Systole
Pressure Changes in Left Ventricular Pressure, Aortic Pressure, and
Jugular Venous Pressure
HEART SOUNDS
S1 and S2, Splitting
HEMODYNAMICS & PERIPHERAL VASCULAR CIRCULATION
BLOOD
COMPONENTS OF THE VASCULATURE
HEMODYNAMIC PARAMETERS
Velocity of Blood Flow
Blood Flow
Resistance (r)
In parallel
In series
Arterioles are the site of greatest resistance, and they are responsible
for the largest drop in arterial pressure
Capacitance (Compliance)
LAMINAR VERSUS TURBULENT FLOW
CAPILLARY FLUID EXCHANGE
Net Filtration Pressure
Net Fluid Flow
Lymphatics
Edema
MEASUREMENT & REGULATION OF ARTERIAL PRESSURE
changes
in CO or SVR affect MAP
Systolic pressure
Diastolic pressure
Pulse pressure
REGULATION OF MEAN ARTERIAL PRESSURE
BARORECEPTOR REFLEX: SHORT-TERM REGULATION OF BLOOD PRESSURE
AUTONOMIC NERVOUS SYSTEM
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM: LONG-TERM REGULATION OF BLOOD
PRESSURE
juxtaglomerular cells
AUTOREGULATION
ELECTROCARDIOGRAPHY
ARRHYTHMIAS
TOC
RESPIRATORY
(Costanzo
BRS 2018) V1
PDF
(Ward
Glance 2017) V1 PDF
(Baillet
20
Respiration silencieuse Sommaire)
V1 JPG
(Baillet
21
Le
souffle et le volume résiduel pulmonaire Sommaire)
V1 JPG
(Baillet
22
Mécanique
respiratoire Sommaire)
V1 JPG
(Baillet
23
Echangeur
pulmonaire i : le versant broncho-alvéolaire Sommaire)
V1 JPG
(Baillet
24
Echangeur
pulmonaire ii : le versant circulatoire (la petite circulation) Sommaire) V1 JPG
(Baillet
25
Contrôle
nerveux de l'homéostasie respiratoire Sommaire)
V1 JPG
CONTENTS
OVERVIEW
breath
(inhalation
- exhalation - obligate - nasal breathing) - respiratory
rate - respirometer - pulmonary surfactant - compliance - elastic
recoil - hysteresivity - airway resistance - bronchial
(hyperresponsiveness - constriction - dilatation) - mechanical
ventilation
FUNCTIONAL ANATOMY
OF THE RESPIRATORY SYSTEM
MECHANICS OF
BREATHING
GAS EXCHANGE
PULMONARY BLOOD
FLOW - CIRCULATION
pulmonary
circulation - hypoxic pulmonary vasoconstriction - pulmonary shunt
LUNG VOLUMES
VC
- FRC- Vt - dead space - CC - PEF
Calculations
: respiratory minute volume - FEV1/FVC ratio
Lung
function tests : spirometry - body plethysmography - peak flow
meter - nitrogen washout
LUNG CAPACITIES
PULMONARY DEAD
SPACE
OXYGEN TRANSPORT
CARBON DIOXIDE
(CO2) TRANSPORT
INTERACTIONS
ventilation
(V)
- Perfusion (Q) (Ventilation/perfusion ratio V/Q scan) - zones of
the lung - gas exchange - pulmonary gas pressures - alveolar gas
equation - alveolar–arterial gradient - hemoglobin - oxygen–hemoglobin
dissociation curve (Oxygen saturation 2,3-BPG Bohr effect Haldane
effect) - carbonic anhydrase (chloride shift) - oxyhemoglobin -
respiratory quotient - arterial blood gas - diffusion capacity (DLCO)
CONTROL OF
RESPIRATION
pons
(pneumotaxic
center - apneustic center) - medulla (dorsal respiratory
group - ventral respiratory group) - chemoreceptors (central -
peripheral) - pulmonary stretch receptors (Hering–Breuer reflex)
RESPIRATORY
RESPONSES TO STRESS
INSUFFICIENCY
high
altitude (death zone) - oxygen toxicity- hypoxia
END OF CONTENTS
OVERVIEW
BECAUSE IT IS
ESSENTIAL FOR METABOLISM, OXYGEN MUST BE PROVIDED IN RELATIVELY LARGE
AMOUNTS TO MOST CELLS
O2
: required to synthesize adenosine triphosphate (ATP)
OXYGEN DELIVERY HAS
THREE STAGES
External
respiration
External
respiration: inhibited by hypoventilation and impaired gas exchange at
pulmonary membrane
Internal
respiration
Internal
respiration : inhibited by CO
Cellular
respiration
Cellular
respiration : inhibited by CO and CN by interfering with electron
transport chain
FUNCTIONAL ANATOMY
OF THE RESPIRATORY SYSTEM
OVERVIEW
Gas exchange occurs
in the respiratory airways
Space within
conducting airways is termed anatomic dead space
CONDUCTING AIRWAYS
Conducting
airways : ↑ resistance because arranged in series
Bronchi
Bronchi
contain supportive cartilage rings that prevent airway collapse during
expiration
Bronchioles : lack
cartilage
Mucociliary tract
Mucociliary
escalator: impaired by smoking, diseases such as cystic fibrosis, and
intubation
Primary ciliary
dyskinesia: immotile cilia; absent dynein arm
Kartagener
syndrome: ciliary dyskinesia in a setting of situs inversus, chronic
sinusitis, and bronchiectasis
Conducting
bronchioles
RESPIRATORY AIRWAYS
Respiratory
airways : site of gas exchange
Respiratory
airways: ↓ resistance because arranged in parallel
PULMONARY MEMBRANE:
THE “AIR-BLOOD” BARRIER
Type
II pneumocytes: synthesize surfactant ; repair cell of lung
MECHANICS OF
BREATHING
OVERVIEW
Ventilation
is the process by which air enters and exits the lungs
Normal ventilation but impaired gas exchange: anemia, high altitude
INSPIRATION
Overview
Diaphragm:
most important muscle of respiration
Accessory muscles:
sternocleidomastoid, scalenes, pectoralis major; important in forceful
breathing
Driving force for
inspiration
Negative
intrapleural pressure: responsible for pressure gradient driving air
into lungs
Boyle’s
law: V2 = P1V1/P2; i.e., as lung volume ↑ during inspiration the
intrapleural pressure must ↓
Transpulmonary
pressure: difference between pleural and alveolar pressures
Sources of
resistance during inspiration
Airways
resistance: friction between air molecules and airway wall caused by air
moving at high velocity
Compliance
resistance: resistance to stretching of lungs during inspiration
Tissue
resistance: friction generated by pleural surfaces sliding over each
other during inspiration
EXPIRATION
Overview
Expiration
during normal breathing: passive process due to elastic recoil of lungs
and chest wall
Expiration
during exercise or in lung disease: active process requiring use of
accessory muscles
Driving forces for
expiration
↑
Intrapleural pressure: caused by movement of diaphragm upward and chest
wall inward
Sources of
resistance during expiration
Airflow
resistance during expiration: primarily due to ↓
airway diameter from ↑
intrathoracic pressure
WORK OF BREATHING
Overview
Work
of breathing: pressure-volume work performed in moving air into and out
of lungs
Airway resistance
Air:
essentially a low-viscosity fluid, so airflow resistance can be
approximated by Poiseuille’s equation
Poiseuille’s
equation: R = 8nl/pir4
Airway
diameter:
small changes can have dramatic impact on airflow resistance
because of inverse relationship of resistance to the fourth power of
radius
Large
airways: contribute most to airway resistance; arranged in series with
small total cross-sectional area
Small airways
provide relatively little resistance: arranged in parallel; large total
cross-sectional area; slow/laminar flow
Compliance
resistance (work)
Compliance
work: work required to overcome elastic recoil of lungs; largest
component of work of breathing
Tissue resistance
Tissue
resistance: normally small component of work of breathing due to
presence of pleural fluid
PULMONARY
COMPLIANCE (C)
This is a measure
of lung distensibility
Lung
compliance: compliant lungs are easy to distend
Defined as the
change in volume (DV) required for a fractional change of pulmonary:
pressure (DP):
Compliance of the
lungs
Compliance
curve of the lungs: compliance greatest in midportion of curve;
demonstrates hysteresis
Compliance of the
combined lung–chest wall system
Lung–chest
wall system: at equilibrium at FRC
PULMONARY ELASTANCE
Elastance is the
property of matter that makes it resist deformation
Elastance:
elastic structures are difficult to deform, e.g., fibrotic lungs
Pulmonary elastance
(E) is the pressure (P) required for a fractional change of lung volume
(DV)
SURFACE TENSION
Surface
tension: created by attractive forces between water molecules; produces a
collapsing pressure
Compliance
of
saline- inflated lungs: greater than air-filled lungs because of ↓
in surface tension and alveolar collapsing pressure
Laplace’s
law: collapsing pressure inversely proportional to alveolar radius; CP =
T/R
ROLE OF SURFACTANT
Surfactant is a
complex phospholipid secreted onto the alveolar membrane by type 2
epithelial cells
Surfactant
reduces compliance resistance of lungs
Surfactant:
complex phospholipid secreted by type II epithelial cells; ↓ alveolar surface tension to ↓
work of breathing
Surfactant reduces
compliance resistance (work) of the lungs
Alveolar
surface tension: moderate amount beneficial because generates collapsing
pressure that contributes to elastic recoil
GAS EXCHANGE
OVERVIEW
Gas
exchange across the pulmonary membrane occurs by diffusion
PARTIAL PRESSURE OF GASES
Dalton’s
law:
partial pressure exerted by a gas in a mixture of gases is
proportional to the fractional concentration of that gas
Dilution
of inspired air by H2O vapor: ↓
partial pressure of alveolar O2; important at high altitude
DIFFUSION
Fick’s
law of diffusion: D = ΔP x A x S/T
Oxygen diffusion:
impaired by any process that ↓ O2 pressure
gradient, ↓
surface area of pulmonary membrane, or ↑ diffusion distance
DIFFUSING CAPACITY OF THE PULMONARY MEMBRANE
Diffusing
capacity:
volume of gas able to diffuse across pulmonary membrane in 1
minute with pressure gradient across membrane of 1 mm Hg
Diffusing
capacity: often measured using CO
O2 exchange normally so efficient that it is perfusion limited
With lung disease O2 exchange may become diffusion limited
PERFUSION-LIMITED & DIFFUSION-LIMITED GAS EXCHANGE
Perfusion-limited exchange
Perfusion-limited
gas exchange: diffusion can ↑ only if
blood flow ↑;
examples: N2O and O2 under normal conditions
Diffusion-limited exchange
Diffusion-limited
gas
exchange: diffusion continues as long as pressure gradient exists
across pulmonary membrane; examples: O2 during vigorous exercise at
high altitude and CO
PULMONARY BLOOD
FLOW
PRESSURES IN THE
PULMONARY CIRCULATION
Pulmonary
hemodynamics:
pulmonary circulation receives entire cardiac output yet
has low pressures compared with systemic circulation
“ZONES” OF PULMONARY BLOOD FLOW
Lung
apices: relatively underperfused in upright position owing to low
arterial hydrostatic pressure at lung apices
Zone 1 blood flow
Zone
1 has no blood flow during the cardiac cycle
Zone 1 blood flow: may be seen with severe hemorrhage and positive-
pressure ventilation
Zone 2 blood flow
Zone
2 has intermittent blood flow during the cardiac cycle
Zone 2 blood flow: no blood flow during diastole because of collapse of
pulmonary capillaries; occurs in upper two thirds of lungs
Zone 3 blood flow
Zone
3 has continuous blood flow during the cardiac cycle
Zone 3 blood flow: primarily occurs in the lung bases
VENTILATION-PERFUSION (V/Q) MATCHING
V/Q
matching: important for efficient gas exchange
V/Q matching: inefficient to perfuse unventilated alveoli or ventilate
nonperfused alveoli
Lung
apices relatively overventilated at rest
Lung bases relatively overperfused at rest
Mechanisms
of V/Q matching: hypoxia-induced vasoconstriction, pulmonary hemodynamic
and ventilatory changes with exercise
Hypoxemia
in pulmonary capillaries stimulates pulmonary arteriolar
vasoconstriction
Hypoxia-induced
vasoconstriction:
mechanism whereby hypoxia-induced vasoconstriction
shunts blood to better-ventilated lung segments
Recruitment:
opening
of previously closed pulmonary capillaries because of increased
pulmonary arterial pressures, as may occur with exercise
Distension: already patent capillaries dilate further to accommodate
additional blood
V/Q matching: occurs more efficiently during exercise
SHUNTS
Anatomic shunt
Anatomic
shunt: blood diverted from lungs; examples: fetal blood flow,
right-to-left intracardiac shunting
Physiologic shunt
Physiologic
shunt:
blood supplying the lungs is not involved in gas exchange;
examples: bronchial arterial circulation, pneumonia, pulmonary edema
LUNG VOLUMES
OVERVIEW
Residual
volume: air left in lungs after maximal expiration; cannot be measured
with spirometry
Lung
volumes: ↓ in
restrictive disease; ↑ in obstructive disease
TIDAL VOLUME (VT)
Tidal
volume: volume of air inspired or expired with each breath;
approximately 500 mL
INSPIRATORY RESERVE VOLUME (IRV)
Inspiratory
reserve volume: volume of air that can be inspired beyond a normal tidal
inspiration
EXPIRATORY RESERVE VOLUME (ERV)
Expiratory
reserve volume: volume of air that can be exhaled after a normal tidal
expiration
RESIDUAL VOLUME (RV)
Residual
volume: can be measured by helium dilution technique
Helium
dilution concept: C1 X V1 = C2 x (V1 + V2)
Air-trapping
in COPD: ↑ residual
volume → ↑
anteroposterior diameter →
“barrel-chested”
appearance
LUNG CAPACITIES
OVERVIEW
Lung
capacities: sum of two or more lung volumes
FUNCTIONAL RESIDUAL
CAPACITY (FRC)
FRC:
equilibrium point at which elastic recoil of the lungs is equal and
opposite to outward force of the chest wall
INSPIRATORY
CAPACITY (IC)
Inspiratory
capacity: maximum volume of air that can be inhaled after a normal tidal
inspiration
VITAL CAPACITY (VC)
Vital
capacity: maximum volume of air expired after maximal inspiration;
synonymous with forced vital capacity
FORCED EXPIRATORY
VOLUME (FEV1) AND FEV1/FVC RATIO
FEV1:
maximum amount of air that can be exhaled in 1 second following a
maximal inspiration
FEV1/FVC
ratio: ↓
with obstructive lung disease, ↑
with restrictive lung disease
TOTAL LUNG CAPACITY
(TLC)
Total
lung capacity: maximum lung volume; ↑
in obstructive disease, ↓
in restrictive disease
PULMONARY DEAD
SPACE
OVERVIEW
Types
of dead space: anatomic, alveolar, physiologic
ANATOMIC DEAD SPACE
Anatomic
dead space: volume of conducting airways not involved in gas exchange
Anatomic dead
space: approximately 1 mL per pound of body weight in lean adults;
increases considerably in mechanically ventilated patients
ALVEOLAR DEAD SPACE
Alveolar
dead space: ventilated alveoli that are not perfused; negligible volume
in healthy young adults
PHYSIOLOGIC
DEAD SPACE
Physiologic dead
space: sum of the anatomic and alveolar dead spaces
Calculation of
physiologic dead space: VD = VT X (PaCO2 - PeCO2)/PaCO2
ALVEOLAR
VENTILATION
Minute
ventilation: respiratory rate X VT; ~ 6 L/min in healthy adult
Alveolar
ventilation: need to consider volume of physiologic dead space
OXYGEN TRANSPORT
OVERVIEW
Oxygen
in blood: exists in two forms: hemoglobin- bound and dissolved (unbound)
Oxygen transport :
O2 poorly soluble in blood; ~
98%
transported bound to hemoglobin
OXYGEN TENSION :
FREE DISSOLVED OXYGEN
Oxygen
tension: pressure exerted by dissolved O2; ~100 mm Hg in
arterial blood
Hypoxemia: refers to ↓
PaO2 (<75 mm Hg)
A-a
gradient: gradient > 10 mm Hg implies defective gas exchange across
pulmonary membrane
OXYGEN CONTENT OF
THE BLOOD
Oxygen-carrying
capacity of the blood: approximately 20 mL/dL, sometimes expressed as
20%
Reduced
oxygen-carrying capacity : anemia, methemoglobinemia
HEMOGLOBIN
Types
of hemoglobin
Fetal hemoglobin:
higher affinity for oxygen, causing right shift of Hb dissociation curve
O2 binding to
hemoglobin
Taut
form of hemoglobin: low affinity for O2
Relaxed form of
hemoglobin: high affinity for O2
Methemoglobinemia:
patients cyanotic (low O2 saturation) despite normal PaO2
Hemoglobin-O2
dissociation curve
Hemoglobin-O2
dissociation curve: sigmoidal shape; ↑ affinity of Hb for O2
at high PaO2, ↓
at low PaO2
CO toxicity: CO
binds Hb →
carboxyhemoglobin →
Hb unable to offload O2 to tissues; treated with hyperbaric oxygen
O2 saturation
(SaO2): percentage of heme groups bound to oxygen
Cyanosis: caused by
presence of ≥ 5 g/dL deoxygenated Hb
Right shift
of O2 dissociation curve: ↑
2,3- DPG, ↑ H+ ions
(acidosis), ↑
CO2 binding to Hb, ↑
body temperature
Left shift of O2 dissociation curve: ↑
pH, ↓ PCO2, ↓ body temperature, ↓
2,3-DPG, ↑ fetal Hb, ↑ CO
CARBON DIOXIDE
(CO2) TRANSPORT
OVERVIEW
Most
CO2 travels in the blood in the form of HCO3- in RBCs
BICARBONATE ION
Chloride
shift: Cl- enters RBCs in exchange for HCO3-; HCO3- then travels “free”
in blood to lungs
Reverse chloride
shift: in pulmonary capillaries HCO3- enters RBCs in exchange for Cl-
→ HCO3- converted to
CO2, which is expired
CARBAMINOHEMOGLOBIN
Bohr
effect: right-shifting of Hb-O2 dissociation curve due to binding of CO2
to Hb
DISSOLVED CO2 (PCO2)
Dissolved
CO2 : CO2 highly soluble in blood relative to O2; ~
10%
CO2 transported in blood in dissolved form
BUFFERING EFFECT OF DEOXYHEMOGLOBIN
Buffering
effect
of deoxyhemoglobin : soaks up H+ ions resulting from HCO3-
production in RBCs, which minimizes drop in pH along the capillary
CONTROL OF
RESPIRATION
OVERVIEW
Control
of respiration : tightly controlled to maintain optimal PaO2 and PaCO
CENTRAL CONTROL
Overview
Basic
control of respiratory rhythm originates from dorsal and ventral
respiratory groups located within the medulla
Fine
control of respiratory rhythm originates from the pneumotaxic and
apneustic centers of the pons
Cortical
influence on respiration: can have a powerful influence; example:
hyperventilation during panic attack
Dorsal respiratory
group
Ventral respiratory
group
Ventral
respiratory group: stimulates expiratory muscles (normally relaxed);
important in forced expiration (e.g., exercise)
Pneumotaxic center
Pneumotaxic
center: located in pons; inhibits inspiration →
↓ lung filling,
↑ breathing rate
Apneustic
center
Apneustic
center: located in pons; ↑
duration of inspiration →
↑ lung filling,
↓ breathing rate
CHEMORECEPTORS
Chemoreceptors:
sensitive to changes in pH, PaO2, and PaCO2
Central
chemoreceptors (chemosensitive areas)
Central
chemoreceptors: stimulate hyperventilation in response to ↑ PaCO2 (rapid response) and ↓
pH (slow response)
Central
chemoreceptor response to ↓ pH [↑
H+]: slow because H+ ions do not directly cross the blood-brain barrier
Central
chemoreceptors: CO2 crosses blood-brain barrier into CSF → reacts with H2O
(slowly) to form H+ ions →
H+ ions directly activate chemoreceptors
Respiratory
response to high altitude: hyperventilation due to hypoxia-induced
stimulation of peripheral chemoreceptors
Peripheral
chemoreceptors
Peripheral
chemoreceptors: located in carotid and aortic bodies with afferents to
the dorsal respiratory group
Peripheral
chemoreceptors: respond to pH, PaCO2, and PaO2
Hypoxia-induced
hyperventilation:
limited effect due to decreasing PaCO2 and H+,
although with lung disease PaCO2 and H+ may not decrease such that
hypoxia remains a potent stimulator of ventilation
MECHANORECEPTORS
& PULMONARY REFLEXES
Irritant receptors
Irritant
receptors:
located in large-diameter airways; promote coughing,
sneezing, and bronchoconstriction in response to noxious agents
Stretch receptors:
the Hering-Breuer reflex
Stretch
receptors:
located in walls of larger-diameter airways; activated by
airway distension and inhibit further inspiration; play protective role
EFFECTS OF EXERCISE
Hyperventilation
Hyperventilation
during exercise: occurs even before changes in blood gas levels are
detectable
Body movements
RESPIRATORY
RESPONSES TO STRESS
HYPOXIA
& HYPOXEMIA
Overview
Hypoxemia:
inadequate O2 in the blood
Hypoxia: inadequate
O2 supply to the tissues
Hypoxemic hypoxia
is the most common cause of hypoxia
Physiologic
responses to hypoxemia
Treatment
of hypoxia: most cases will respond to supplemental O2; histotoxic
hypoxia will not
High-altitude
respiration
BREATHING DISORDERS
-
UNSORTED
-
CONTROL
OF BREATHING
GAS EXCHANGE &
TRANSPORT
HYPOXIA
LUNG
PULMONARY
CIRCULATION
-
LUNG
FUNCTION, RESPIRATION
MECHANICS
OF BREATHING
PURIFICATION
OF RESPIRATORY AIR
ARTIFICIAL
RESPIRATION
PNEUMOTHORAX
LUNG
VOLUMES AND THEIR MEASUREMENT
DEAD
SPACE, RESIDUAL VOLUME, AIRWAY RESISTANCE
PRESSURE-VOLUME
CURVE OF LUNG AND THORAX, RESPIRATORY WORK
SURFACE
TENSION, SURFACTANT
DYNAMIC
LUNG FUNCTION TESTS
PULMONARY
GAS EXCHANGE
PULMONARY
BLOOD FLOW, VENTILATION-PERFUSION RATIO
ALVEOLAR-ARTERIAL
OXYGEN DIFFERENCE (AA0O.)
C01
TRANSPORT IN BLOOD
C02
BINDING IN BLOOD, C02 IN CSF
C01
IN CEREBROSPINAL FLUID
BINDING
AND TRANSPORT OF 02 IN BLOOD
INTERNAL
(TISSUE) RESPIRATION, HYPOXIA
RESPIRATORY
CONTROL AND STIMULATION
EFFECTS
OF DIVING ON RESPIRATION
EFFECTS
OF HIGH ALTITUDE ON RESPIRATION
OXYGEN
TOXICITY
-
LUNG
VOLUMES & CAPACITIES - PRESSURES & VOLUMES DURING NORMAL
BREATHING
Tidal volume
Inspiratory reserve
volume
Expiratory reserve
volume
Residual volume
Inspiratory
capacity
Functional residual
capacity
Vital capacity
Total lung capacity
Work
of breathing
Measurement
of Lung Volumes and Capacities
Dilution tests
Body
plethysmography
Anatomic
Dead Space
Physiologic
Dead Space (Total Dead Space) -
Determination of physiologic dead space
GAS
LAWS
DIFFUSION
VENTILATION
Alveolar
Function
Gas Exchange
Surface Tension
Surfactant
Other Lung Products
Ventilation
Rate
Minute Ventilation
Alveolar
Ventilation
Inspiration
Expiration
Lung
Compliance
Compliance
of the Lung–Chest Wall System
Lung and chest wall
Elastic
recoil
Compliance
Hysteresis
Mechanics of Breathing During the Respiratory Cycle
LUNG MECHANICS: ELASTIC FORCES
LUNG MECHANICS: AIRWAY RESISTANCE
Forces
Defined
At Rest
During
Inspiration
At Maximum Inspiration
During Expiration
At Maximum
Expiration
Mechanical Ventilation
Airways
Flow
Resistance Factors That Influence
Pulmonary Resistance
BLOOD
GASES
Oxygen
Transport CARRIAGE OF
Hemoglobin
Oxygen content of
blood
Oxygen-Hemoglobin
Dissociation Curve
Methemoglobin
Cyanide
vs carbon monoxide poisoning
Carbon
Dioxide Transport CARRIAGE
OF
ACID–BASE
BALANCE
Respiratory
Acid-Base Disturbances DISORDERS
Pulmonary
Circulation -
AND ANATOMICAL RIGHT-TO-LEFT SHUNTS
Characteristics
Distribution of
Pulmonary Blood Flow
Regulation of
Pulmonary Blood Flow
Pulmonary
vascular resistance
VENTILATION–PERFUSION
MISMATCHING
Alveolar
gas equation
EXERCISE,
ALTITUDE AND DIVING Response to high altitude Response to exercise
Hypoxemia
Etiology
Hypercapnia
Control
of Respiration - CONTROL OF BREATHING
CHEMICAL
MECHANISMS
NEURAL
MECHANISMS
Central Control of
Respiration
Chemoreceptors
Other Receptors
END
OF UNSORTED
TOC
RENAL
ACID-BASE SALT & WATER
(Baillet 26 Rein
i : fonction glomerulaire Sommaire) V1 JPG
(Baillet 27 Systèmes
tubulaires Sommaire) V1 JPG
(Baillet 28 Système
rénal autoregule et maillon régulateur asservi Sommaire) V1 JPG
(Baillet 29 Excrétion
urinaire Sommaire) V1 JPG
CONTENTS
CREATING URINE -
FORMATION OF URINE
FILTRATION
Renal
blood flow- Renal plasma flow-- Ultrafiltration- Countercurrent
exchange- Filtration fraction
REABSORPTION
Solvent
drag - Sodium - Chloride - Urea- Glucose- Oligopeptides- Protein
Indirect
Influence of
hormones
Antidiuretic
hormone - Aldosterone
SECRETION
Clearance
- Pharmacokinetics - Clearance of medications - Urine flow rate
OTHER FUNCTIONS
HORMONE SECRETION
Atrial
natriuretic peptide - Renin - Erythropoietin - Calcitriol-
Prostaglandins
MAINTAINING
HOMEOSTASIS
Glucose
Oligopeptides,
proteins, and amino acids
Urea
Sodium
Chloride
Water
Bicarbonate
Protons
Potassium
Calcium
Magnesium
Phosphate
Carboxylate
Acid–base
balance
Darrow
Yannet diagram - Base excess - Davenport diagram - Anion ga (Delta
ratio)- Winters' formula - Buffering
(Bicarbonate buffer
system Respiratory compensation Renal compensation)
Osmolality
Fluid
balance
Body
water : Intracellular fluid/Cytosol
Extracellular fluid
(Interstitial fluid Plasma Transcellular fluid)
BLOOD PRESSURE
GLUCOSE FORMATION
ASSESSMENT &
MEASUREMENT OF RENAL FUNCTION
Glomerular
filtration
rate - Creatinine clearance - Augmented renal clearance -
Renal clearance ratio - Urea reduction ratio - Kt/V -Standardized Kt/V
- Dialysis adequacy (Hemodialysis product) - PAH clearance (Effective
renal plasma flow Extraction ratio)
OTHER
Fractional
excretion of sodium - BUN-to-creatinine ratio - Tubuloglomerular
feedback - Natriuresis - Urine
OVERVIEW
REGULATION OF GLOMERULAR FUNCTION
MEASURING RENAL FUNCTION
RENAL TRANSPORT MECHANISMS
HANDLING OF SPECIFIC SUBSTANCES ALONG THE NEPHRON
CONCENTRATION AND DILUTION OF URINE
RENAL CONTROL OF PLASMA POTASSIUM
RENAL CONTRIBUTION TO CONTROL OF PHOSPHATE & CALCIUM HOMEOSTASIS
DIURETICS
END OF CONTENTS
OVERVIEW
GENERAL
FUNCTIONS OF THE KIDNEYS
Excretion of
unneeded substances : excess water, electrolytes, potentially toxic end
products of metabolism
Reclamation of
needed substances : water, electrolytes, glucose, bicarbonate
Renal contribution
to homeostasis: regulates ECF volume, osmolality, acid-base status
FUNCTIONAL
ANATOMY OF THE KIDNEY
Renal perfusion:
highly perfused; receives approximately 25% of cardiac output
STRUCTURE
OF THE FILTRATION UNIT: THE NEPHRON
Nephron: basic
functional unit of kidney; approximately 1 million per kidney
Glomerulus:
expansion of afferent arteriole into capillary bed across which
filtration occurs
THE
GLOMERULAR FILTRATION BARRIER
Function
of the filtration barrier
Filtration barrier:
prevents filtration of cells and large proteins
Layers
of the filtration barrier
Layers of
filtration barrier: fenestrated endothelium, negatively charged basement
membrane, visceral epithelial cells
Fenestrated
endothelium: allows for large volume filtration across glomerulus
Negatively charged
basement membrane: prevents passage of negatively charged proteins such
as albumin
REGULATION
OF GLOMERULAR FUNCTION
FILTRATION
FORCES AT THE GLOMERULUS
Starling forces promoting filtration : glomerular
hydrostatic pressure (large) and Bowman space oncotic pressure (small)
Starling forces opposing filtration : glomerular
oncotic pressure and Bowman space hydrostatic pressure
GLOMERULAR
FILTRATION RATE (GFR)
OVERVIEW
GFR : equivalent to
summated filtration volume of all glomeruli each minute
GFR dependent on
glomerular filtration forces, glomerular permeability, glomerular
surface area
GFR : high
filtration rate due to ↑
capillary permeability and ↑
glomerular hydrostatic pressures
CALCULATION
OF GFR
Glomerular marker:
substance that is freely filtered and neither secreted nor reabsorbed
along the nephron
Inulin: ideal
marker for measuring GFR because it is freely filtered and neither
reabsorbed nor secreted along the nephron
FILTRATION
FRACTION
Filtration fraction
= GFR/RPF; typical value 20%
REGULATION
OF GFR
Overview
Regulation of GFR:
occurs primarily through regulation of glomerular hydrostatic pressure
Systemic
arterial pressure
Glomerular
hydrostatic pressure remains relatively constant (despite varying
systemic arterial pressures) due to intrinsic autoregulatory mechanisms
Regulation of glomerular hydrostatic pressure: primarily depends on
afferent and efferent arteriolar resistances
Afferent
arteriolar resistance
Efferent
arteriolar resistance
Efferent arteriolar
vasoconstriction: mild → ↓ RBF, ↑
GFR; marked: ↓
RBF, ↓ GFR
RENAL
BLOOD FLOW
Overview
Etiology of renal
artery stenosis : fibromuscular hyperplasia in young women,
atherosclerotic disease in older adults
Autoregulation
of renal blood flow
Autoregulation :
ensures relatively constant RPF, GFR, and distal flow in face of widely
varying systemic arterial pressures
Autoregulation :
occurs through tubuloglomerular feedback and myogenic mechanism
Myogenic
mechanism
Myogenic response
to increased renal perfusion: reflexive constriction of afferent
arteriole →
minimizing ↑
in RPF, GFR, and glomerular damage
Tubuloglomerular
feedback
Tubuloglomerular
feedback: mechanism whereby flow of NaCl to macula densa influences RPF
and GFR
Tubuloglomerular
feedback: dependent on signal (NaCl delivery), sensor (macular densa),
and effector (VSMCs of afferent arteriole)
MEASURING
RENAL FUNCTION
OVERVIEW
Renal function :
refers to rate at which kidneys remove toxins from blood
CLEARANCE
Clearance: volume
of plasma from which a substance has been completely cleared by the
kidneys per unit of time
CALCULATING
CLEARANCE
Curea < GFR,
indicating net reabsorption of urea
MEASURING
THE GFR
Creatinine
clearance
Creatinine
clearance: used as rough approximation of GFR
GFR = V x Ucr/Pcr
Creatinine
clearance: slightly overestimates GFR due to tubular secretion
Inulin
clearance
Inulin clearance :
more accurate estimate of GFR,but its use is clinically impractical
CLEARANCE
& REABSORPTION / SECRETION
Overview
Clearance = GFR if
substance freely filtered and neither reabsorbed nor secreted
Clearance < GFR
if substance freely filtered but undergoes net reabsorption; example:
urea
Clearance > GFR
if substance freely filtered but undergoes net secretion; example: PAH
USING
CLEARANCE VALUES TO ESTIMATE EFFECTIVE RENAL PLASMA FLOW
PAH: clearance
approximates RBF because freely filtered and very efficiently secreted
True RPF = CPAH
/0.90
RBF = RPF/1 -
hematocrit
RENAL
TRANSPORT MECHANISMS
OVERVIEW
Life-threatening
fluid and electrolyte abnormalities would rapidly occur if most of the
filtrate were not reabsorbed
GENERAL TUBULAR FUNCTION
Two routes of transport
across tubular epithelium: transcellular, paracellular
Transcellular route
Transcellular
transport: transport across tubular epithelial cells to peritubular
capillaries; responsible for bulk of transport
Paracellular
transport
Paracellular
transport: across tight junctions that vary in their permeability
throughout the nephron
REABSORPTION OF SALT & WATER
Reabsorption from the proximal tubule
Transcellular
transport in proximal tubule: primarily driven by activity of the
Na+,K+-ATPase pump
Na+,K+-ATPase
pump: maintains low intracellular [Na+] and negatively charged
intracellular environment →
Na+ transcellular transport
Isosmotic
reabsorption: reabsorption of fluid along the proximal tubule in which
there is no change in tubular osmolality
Reabsorption into the peritubular capillaries
High oncotic
pressure in peritubular capillaries promotes reabsorption of fluid from
interstitium into peritubular capillaries
Low hydrostatic pressure in peritubular capillaries also promotes fluid
reabsorption from interstitium into peritubular capillaries
Glomerulotubular balance
Glomerulotubular
balance: balance among GFR, peritubular oncotic pressure, and proximal
tubular reabsorption
Response to
volume-depleted state : ↓ RPF → ↑
filtration fraction to maintain GFR →
↑
peritubular oncotic pressure →
↑ proximal
tubular reabsorption →
↑ ECF
volume
Response to
volume- expanded state: ↑ RPF → ↓
filtration fraction to maintain GFR →
↓
peritubular oncotic pressure → ↓
proximal tubular reabsorption →
↑ urinary
losses →
↓ ECF
volume
TRANSPORT MAXIMUM (Tm)
Transport
maximum: maximum rate at which a substance can be reabsorbed from the
tubular fluid
Filtered
load = plasma concentration of substance x GFR
If
renal load > Tm → substance
accumulates in urine
TUBULAR SECRETION
Route of
secretion: peritubular capillaries
→ tubular epithelial
cells
→ tubular lumen
→ urine
Secreted substances:
uric acid, salicylic acid, bile salts, ketoacids, PAH
Diuretics
lose their effectiveness in renal failure as they are less able to enter
the tubular lumen
Organic
transporters: relative lack of specificity; saturable; can be
competitively inhibited
PATHOPHYSIOLOGY OF RENAL TRANSPORT MECHANISMS
HANDLING
OF SPECIFIC SUBSTANCES ALONG THE NEPHRON
SODIUM
& WATER
OVERVIEW
Kidneys play a
critical role in preventing loss of excess NaCl and water
GENERAL
MECHANISMS OF NA+ REABSORPTION
Stoichiometry of
Na+,K+-
ATPase pump: generates
low intracellular [Na+]
and intracellular
electronegative potential,
both of which drive Na+
from tubular lumen into
peritubular epithelial cell
Secondary active
transport: energy created by Na+ diffusing down its electrochemical
gradient drives transfer of other charged substances into tubular
epithelial cell
REABSORPTION
ALONG THE PROXIMAL TUBULE
Leaky tight
junctions in proximal tubular: prevent creation of osmotic and
concentration gradients for solutes (and water), which are linked to
Na+ reabsorption
Tight junctions in
distal
nephron: allow for the
excretion of a
concentrated urine and a
significant acid load
REABSORPTION
OF NA+ & H2O ALONG THE LOOP OF HENLE (LOH)
REABSORPTION
OF NA+ & H2O IN THE DISTAL NEPHRON
Na+ and Cl-
transport in the distal nephron is flow dependent
REGULATION
OF NA+ BALANCE
CONCENTRATION
& DILUTION OF URINE
OVERVIEW
Kidneys are the
body’s
major route of solute and
water excretion
Urine concentration
can vary
from 50 mOsm/L to
1200 mOsm/L in healthy
young adults
OBLIGATORY
URINE OUTPUT
Obligatory urine
output: minimum amount of urine needed to be produced daily to excrete
metabolic waste products
THE
INTERSTITIAL OSMOTIC GRADIENT FROM CORTEX TO MEDULLA
To remove excess
water, the kidney must be able to excrete a dilute urine
Excretion of excess
water: water channels in distal nephron are closed
To remove excess
solute, the kidney must be able to excrete a concentrated urine
Production of
concentrated urine : occurs as a result of the collecting ducts passing
through a hyperosmolar region with the aquaporin channels open so water
diffuses into the interstitium
The ability of
the kidney to produce a concentrated urine hinges on the creation and
maintenance of a region of high interstitial osmolality
The
countercurrent mechanism
Countercurrent
mechanism: dependent on hairpin structure of vasa recta and LOH, active
NaCl transport from the thick limb of the LOH, and urea trapping within
medullary interstitium
The
loop of Henle as a countercurrent system
Antidiuretic
hormone and control of urine concentration
The distal nephron
delivers a very dilute tubular fluid to the collecting tubules
Plasma
osmolality
Renal
responses to changes in plasma osmolality
Permeability of
medullary collecting ducts to H2O: dependent on presence or absence of
ADH
ADH: increases
distal nephron permeability to H2O and stimulates thirst
The inner medullary
collecting tubules are variably permeable to urea; permeability ↑ in presence of ADH
Urea
trapping
ADH
↑ urea
permeability of inner medullary collecting duct →
urea exits tubular lumen to create more hypertonic interstitium → ↑
[urine]
Vasa
recta
Vasa recta:
capillary network that supplies the nephron
RENAL
CONTROL OF PLASMA POTASSIUM
OVERVIEW
Potassium
distribution: ~
98%
of potassium is intracellular
Acute kidney
injury: often results in hyperkalemia
REGULATION
OF POTASSIUM DISTRIBUTION
Na+,K+-ATPase pump:
regulated by insulin, catecholamines, and K+
CONTROL
OF POTASSIUM HOMEOSTASIS
OVERVIEW
RENAL HANDLING OF POTASSIUM
Distal nephron has
final say on potassium handling
Mechanism
of potassium secretion by distal nephron
Lumen negativity
(as occurs with Na+ reabsorption) →
↑ K+
secretion
↑ Tubular flow
rate → ↑ K+ secretion
Regulation of renal potassium secretion
& reabsorption
Aldosterone promotes K+ secretion by ↑
activity of basolaterally located Na+, K+-ATPase pump and by ↑ number of open Na+ and
K+ channels in luminal membrane
Principal cells:
important in Na+ absorption and K+ secretion
Intercalated cells:
secretes H+ ions; critical role in acid-base balance
RENAL
CONTRIBUTION TO CONTROL OF PHOSPHATE & CALCIUM HOMEOSTASIS
OVERVIEW
Phosphate
concentration regulated by PTH, calcium, and calcitriol
PARATHYROID
HORMONE
Hypocalcemia → ↑
[PTH] → ↑ release Ca2+ and PO4- from bone and ↑
reabsorption of renally filtered Ca2+
PTH: prevents
hyperphosphatemia by ↑renal
phosphate excretion
Hyperphosphatemia
(as in renal failure): stimulates PTH secretion
VITAMIN
D
Calcitriol: most
active form of vitamin D; PTH and calcitriol regulate phosphate balance
Hypophosphatemia: ↑ calcitriol synthesis
Hyperphosphatemia: → ↓
calcitriol synthesis
HYPOPHOSPHATEMIA
& HYPERPHOSPHATEMIA
DIURETICS
OVERVIEW
DIURETICS
& SODIUM
UNSORTED
-
BLADDER
KIDNEY
RENAL ABSORPTION, REABSORPTION & SECRETION
RENAL FILTRATION
-
KIDNEY
STRUCTURE & FUNCTION
RENAL
CIRCULATION
GLOMERULAR
FILTRATION & OEARANCE
TRANSPORT
PROCESSES AT THE NEPHRON
REABSORPTION
OF ORGANIC SUBSTANCES
EXCRETION
OF ORGANIC SUBSTANCES
REABSORPTION
OF NA• AND A-
REABSORPTION
OF WATER, FORMATION OF CONCENTRATED URINE
BODY
FLUID HOMEOSTASIS
SALT
AND WATER REGULATION
DIURESIS
AND DIURETICS
THE
KIDNEY & ACID-BASE BALANCE
REABSORPTION
AND EXCRETION OF PHOSPHATE, CA2• AND MGL+
POTASSIUM
BALANCE
TUBULOGLOMERULAR
FEEDBACK, RENIN-ANGIOTENSIN SYSTEM
-
CONCEPTS
OF TRANSPORT
DEFINITIONS
Quantity
Concentration
FORMS
OF TRANSPORT
Concepts of
Transport
Transcellular
transport
Paracellular
transport
Passive Transport
Simple diffusion
Facilitated
diffusion
Nonionic diffusion
Osmosis
Osmotic pressure
Active Transport
Primary active
transport
Secondary active
transport
Cotransport
(symport)
Countertransport
(antiport)
Rate-Limited
Transport
FLUID
COMPARTMENTS
Composition of
Extracellular Fluid and Intracellular Fluid
HIKIN’: HIgh K+
INtracellularly
ESTIMATING
AND MEASURING FLUID COMPARTMENT VOLUME
Estimating Body
Fluid Volumes
Measuring Body
Fluid Volumes
INTERCOMPARTMENTAL
WATER DYNAMICS
ECF
PATHOPHYSIOLOGY KEY FACTS
Iso-osmotic volume
contraction
Hypo-osmotic volume
expansion
GENERAL
RENAL PHYSIOLOGY
RENAL
CLEARANCE: GENERAL CONCEPTS
Renal Clearance
(Cx)
GLOMERULAR
FILTRATION BARRIER
Fenestrated
capillary endothelium
Glomerular basement
membrane (GBM) - Basement membrane with type IV collagen chains and
heparan sulfate
Podocytes -
Visceral epithelial layer consisting of podocyte foot processes (FPs)
Glomerular Filtrate
Glomerular
Filtration Rate - GFR
Inulin
Creatinine
RENAL
BLOOD FLOW
REGULATION
MECHANISMS
Influencing Factors
Sympathetic nervous
system
Prostaglandins/bradykinin
Angiotensin II
Dopamine
AUTOREGULATION
MECHANISMS - RENAL BLOOD FLOW AUTOREGULATION
Stretch mechanism -
Myogenic
Tubuloglomerular
feedback mechanism
MEASUREMENT
OF RENAL PLASMA AND BLOOD FLOW
Renal Plasma Flow
True Renal Plasma
Flow - Effective renal plasma flow
Renal Blood Flow
Filtration Fraction
- FF
Changes in
Filtration Fraction
Changes in
glomerular dynamics
Calculation of
reabsorption and secretion rate
CONCEPTS
OF REABSORPTION AND SECRETION
Glucose - Glucose
clearance
Amino Acids
Urea
Para-Aminohippuric
Acid
Free Water
Urine Osmolarity
NEPHRON
-TRANSPORT- PHYSIOLOGY & THE TUBULAR SYSTEM
Glomerulus
Proximal Tubule -
Early PCT
Loop of Henle
Thin descending
limb loop of Henle
Thin ascending limb
loop of Henle
Thick ascending
limb is a diluting segment
Early Distal
Convoluted Tubule - Early DCT
Late Distal Tubule
and Collecting Ducts - Collecting tubule
Countercurrent
Multiplier System
Countercurrent
Exchanger (Vasa Recta)
RENAL
TUBULAR DEFECTS Order: Fanconi’s BaGeLS Hereditary disorders of
tubular transport
Fanconi syndrome
Bartter syndrome
Gitelman syndrome
Liddle syndrome
Syndrome of
Apparent Mineralocorticoid Excess
Relative
concentrations along proximal tubule
KIDNEY
ENDOCRINE - HORMONE- FUNCTIONS
Erythropoietin
Vitamin D:
Formation of 1,25-Dihydroxycholecalciferol in the Kidneys - Calciferol
(vitamin D)
Prostaglandins
Dopamine
HORMONES
ACTING ON THE KIDNEY
Atrial Natriuretic
Peptide
Parathyroid Hormone
Renin-Angiotensin-Aldosterone
System
Renin
ACE
AT II
ANP, BNP
ADH (vasopressin)
Aldosterone
Potassium shifts
ACID-BASE
HOMEOSTASIS
ACIDS
AND BASES
Acids
Bases
Buffers
ACID
PRODUCTION
Volatile Acid
Nonvolatile Acid
PHYSIOLOGIC
BUFFERS
Intracellular
Buffers
Proteins
Organic phosphates
Extracellular
Buffers
Major
Minor
ACID-BASE
HOMEOSTASIS
Buffer Systems
Physiologic pH
Acidemia versus
acidosis
Alkalemia versus
alkalosis
ACID-BASE
HOMEOSTASIS : THE KIDNEY
Renal production of
H+ and HCO3–
Secretion of H+
Secretion as H2PO4–
Secretion as NH4+
Reabsorption of
HCO3–
ACID-BASE
HOMEOSTASIS : THE LUNGS
Compensation states
Metabolic alkalosis
Metabolic acidosis
Derangement states
METABOLIC
ACIDOSIS/ALKALOSIS
Metabolic Acidosis
Metabolic Alkalosis
RESPIRATORY
ACIDOSIS/ALKALOSIS
Respiratory
Acidosis
Respiratory
Alkalosis
ACID-BASE
CLINICAL IMPLICATIONS
Acid-Base Nomogram
ACID-BASE
PROBLEM SOLVING
Acidosis and
alkalosis
Renal tubular
acidosis
-
END
OF UNSORTED
TOC
GASTROINTESTINAL & NUTRITION &
METABOLISM
(Baillet 30 Motricité
Digestive Sommaire) V1 JPG
(Baillet 31 Sécretion Digestives Sommaire) V1 JPG
(Baillet 32 Homéostasie
métabolique i : les lieux du métabolisme Sommaire) V1 JPG
(Baillet 33
Le foie Sommaire) V1 JPG
(Baillet 34 Homéostasie
nutritionnelle Sommaire) V1 JPG
(Baillet 35 Système
hypothalamo-hypophysaire Sommaire) V1 JPG
(Baillet 36 Hormones
métaboliques : axe entero-pancréatique et axe somatotrope Sommaire) V1 JPG
(Baillet 37 Thyroïde
et hormones iodées Sommaire) V1 JPG
(Baillet 38 Corticosurrénales
Sommaire) V1 JPG
(Baillet 39 Homéostasie
metabolique ii : les flux et les moments du metabolisme Sommaire) V1 JPG
(Baillet 40 Homéostasie
thermique Sommaire) V1 JPG
(Baillet 41 Homéostasie
phospho-calcique Sommaire) V1 JPG
(Baillet 42 Homéostasie
circulatoire a long terme (hydro-electrolytique) Sommaire) V1 JPG
(Baillet 43 Homéostasie
acido-basique Sommaire) V1 JPG
(Baillet 44 L'exercice
physique Sommaire) V1 JPG
(Baillet 45 Rythmes
biologiques Sommaire) V1 JPG
CONTENTS
-
GI
TRACT
UPPER
Exocrine
Chief cells
(Pepsinogen) - Parietal cells (Gastric acid - Intrinsic factor) -
Foveolar cells (HCO3− - Mucus) - Goblet cells (Mucus)
Processes
Swallowing -
Vomiting - Gastric Emptying
Fluids
Saliva - Gastric
acid
Gastric
Acid Secretion
Gastrin (G cells) -
Histamine (ECL cells) - Somatostatin (D cells)
LOWER
ENDOCRINE/PARACRINE
Bile
& pancreatic secretion
Enterogastrone -
Cholecystokinin (I cells) - Secretin (S cells)
Glucose
homeostasis (incretins)
GIP
(K cells) - GLP-1 (L cells)
Endocrine cell types
Enteroendocrine
cells - Enterochromaffin cell - APUD cell
FLUIDS
Intestinal
juice
PROCESSES
Segmentation
contractions - Migrating motor complex - Borborygmus - Defecation
ENS
Submucous plexus -
Myenteric plexus
EITHER
/ BOTH
Processes
Peristalsis
(Interstitial cell of Cajal - Basal electrical rhythm) - Gastrocolic
reflex - Digestion - Enterocyte
ACCESSORY
Fluids
Bile -
Pancreatic juice
Processes
Enterohepatic
circulation
ABDOMINOPELVIC
Peritoneal
fluid
-
MOTILITY
Stimulation
Contraction patterns
Peristalsis
Segmentation
SECRETION - secretory products
Gastric acid
Intrinsic factor
Pepsin
Bicarbonate
Ions
Digestive enzymes
Mucus
Bile Bilirubin
Locations
of gastrointestinal secretory cells
Pancreatic secretions
α-amylase
Lipases
Proteases
Trypsinogen
REGULATION
Long reflexes
Short reflexes
Gastrointestinal peptides - regulatory substances
Gastrin
Somatostatin
Cholecystokinin
Secretin
Glucose-dependent insulinotropic peptide GLP1 ?
Motilin
Vasoactive intestinal polypeptide
Nitric oxide
Ghrelin
DIGESTION
Carbohydrate absorption
Vitamin and mineral absorption
carbohydrates
(monosaccharide, disaccharide)
proteins
lipids
SPLANCHNIC CIRCULATION
Superior mesenteric artery
Inferior mesenteric artery
Peyer patches
-
STRUCTURE
& FUNCTION OF THE GASTROINTESTINAL TRACT
SALIVATION
& MASTICATION
ESOPHAGUS
STOMACH
PANCREAS
LIVER
& BILIARY TREE
SMALL
INTESTINE
LARGE
INTESTINE
-
LIVER
STRUCTURE
GROSS ANATOMY
Lobes
Surfaces
Impressions
MICROSCOPIC ANATOMY
FUNCTIONAL ANATOMY
COUINAUD
CLASSIFICATION SYSTEM
GENE AND PROTEIN
EXPRESSION
DEVELOPMENT
FETAL BLOOD SUPPLY
FUNCTIONS
BLOOD SUPPLY
BILIARY FLOW
METABOLISM
PROTEINS PRODUCED
& SECRETED BY THE LIVER
MAJOR PLASMA
PROTEINS
FACTORS IN
HEMOSTASIS AND FIBRINOLYSIS
CARRIER PROTEINS
HORMONES
PROHORMONES
APOLIPOPROTEINS
CARBOHYDRATE
METABOLISM
PROTEIN METABOLISM
LIPID METABOLISM
BREAKDOWN
BLOOD RESERVOIR
LYMPH PRODUCTION
OTHER
WITH AGING
CLINICAL
SIGNIFICANCE
DISEASE
SYMPTOMS
DIAGNOSIS
LIVER REGENERATION
LIVER
TRANSPLANTATION
-
END
OF CONTENTS
STRUCTURE
&
FUNCTION OF THE GASTROINTESTINAL TRACT
FUNCTIONAL
ANATOMY
OVERVIEW
Vascular supply of
intestinal tract: foregut— celiac artery; midgut— SMA; hindgut—IMA
LAYERS
OF THE GUT WALL
Mucosa
Mucosa: composed of
mucosal epithelium, lamina propria, and muscularis mucosae
Epithelial cells:
stratified squamous in esophagus, columnar in GI until dentate line,
squamous in rectum
Metaplasia:
transformation of one adult cell type into another
Submucosa
Submucosa: contains
blood vessels, lymphatic vessels, and nerves (submucosal plexus), which
supply the mucosa
Muscularis
propria (externa)
Serosa
Serosa:
absent in certain parts of the intestinal tract, such as the esophagus
NEURAL
REGULATION OF THE GASTROINTESTINAL TRACT
Enteric
nervous system
Enteric nervous
system: composed of submucosal and myenteric plexuses and entirely
contained within gut wall
Submucosal plexus:
stimulates secretion, promotes digestion
Myenteric plexus:
promotes motility of intestinal tract
Extrinsic
regulation : autonomic nervous system
PNS: promotes
digestion and absorption by stimulating secretions and intestinal
motility
SNS: inhibits
digestion and absorption in part through vasoconstriction of the
splanchnic circulation
Anatomy
of reflex loops
Gastrocolic reflex:
gastric distension promotes bowel movement
Vagovagal
reflexes: afferents from stretch receptors, chemoreceptors, and
osmoreceptors in the gut travel to and from the central nervous system
through the vagus nerve
GASTROINTESTINAL
FUNCTIONS
MOTILITY
Electrical
basis for intestinal motility: slow waves
Intestinal SMCs:
resting membrane potential unstable and continually depolarizing
Slow waves → threshold potential
reached →
action potential generated →
smooth muscle contraction →
propulsion of intestinal contents toward anus
Types
of contractions
Peristalsis:
dependent on functional myenteric plexus
Segmentation:
simultaneous contractions proximal and distal to food bolus; promotes
digestion; no forward propulsion of food bolus
Tonic contractions
of sphincter muscles prevent premature analward passage of intestinal
contents
DIGESTION
Digestion:
enzymatic hydrolysis of macromolecules into absorbable smaller compounds
ABSORPTION
Efficient
absorption: dependent on large surface area of mucosal epithelium
SALIVATION
&
MASTICATION
SALIVATION
Composition & functions of saliva
Mechanism of saliva production
Saliva:
usually hypotonic relative to plasma when secreted
Types of salivary glands
Salivary
glands: two types—serous and mixed
Regulation of salivation
MASTICATION
Muscles
of mastication: masseter, temporalis, medial and lateral pterygoids
ESOPHAGUS
FUNCTIONAL
ANATOMY
ESOPHAGEAL
MOTILITY
Overview
Swallowing: under
both voluntary and involuntary control
Upper third of
esophagus composed of striated muscle, lower third composed of smooth
muscle that is controlled by myenteric plexus
Opening
of the upper esophageal sphincter
Peristalsis:
coordinated muscular contraction
Opening
of the lower esophageal sphincter (LES)
LES: normally
tonically constricted, which helps prevent gastric reflux
STOMACH
OVERVIEW
Stomach: holding
area for food; converts food to chyme and releases small aliquots to
duodenum
GASTRIC
RESPONSE TO A MEAL: PHASES OF DIGESTION
Cephalic phase:
sight,
smell, or thought of food
stimulates gastric
secretions
Gastric phase:
abdominal
distension from food
bolus triggers gastric
secretions
Enteric
(intestinal) phase:
entry of chyme into small
bowel stimulates release
of factors that slow gastric
emptying
RECEPTIVE
RELAXATION OF THE STOMACH
Receptive
relaxation:
reflexive relaxation of
stomach in response to
food descending through
lower esophagus
Gastric
accommodation:
relaxation of the stomach
in response to gastric
distension
GASTRIC
CELL TYPES & THEIR SECRETIONS
Parietal
cells
Low gastric pH:
denatures protein, activates proteases, inhibits bacterial growth
Intrinsic factor:
binds vitamin B12 to prevent its degradation in small bowel
G
cells
G cells: secrete
gastrin, promote parietal cell activity
Gastrin secretion:
stimulated by presence of protein in stomach
Chief
cells
Chief cells secrete
pepsinogen, which when cleaved to pepsin initiates protein digestion in
stomach
Mucous
cells
Mucous cells:
secretion of mucus and HCO3-, both of which prevent mucosal damage from
low gastric pH
GASTRIC
MOTILITY : REGULATION OF GASTRIC EMPTYING
Overview
Gastric emptying is
delayed by a high-fat meal
Gastric motility
and pyloric sphincter tone: regulated by hormones produced in small
intestine
Secretin
Secretin:
secretion stimulated by acidic chyme entering duodenum; promotes HCO3-
-rich secretion from pancreas and inhibits further gastric emptying
Cholecystokinin
(CCK)
CCK: secretion
stimulated by entry of fatty acids into duodenum; prevents further
gastric emptying by inhibiting pyloric sphincter relaxation; stimulates
gallbladder contraction
Other
hormones
Gastric inhibitory
peptide and somatostatin generally inhibit digestion
PANCREAS
FUNCTIONAL
ANATOMY
Pancreas:
retroperitoneal organ with important endocrine and exocrine functions
PANCREATIC
SECRETIONS
Acinar secretions:
enzyme-rich secretion critical for digestion
Ductal secretions:
HCO3--rich secretions that neutralize acidic chyme; allow digestive
enzymes to function
PATHOPHYSIOLOGY
Pancreatitis: most
common causes are alcohol abuse and obstructing gallstones
LIVER
&
BILIARY TREE
FUNCTIONAL
ANATOMY
GALLBLADDER
Functions of bile:
solubilization of cholesterol, dietary fat absorption, excretion of
waste products
ENTEROHEPATIC
CIRCULATION
Enterohepatic
circulation: cycling of substances such as bile acids between liver and
intestinal tract
Cholesterol
excretion: primarily occurs through the loss of bile acids in feces
SMALL
INTESTINE
FUNCTIONAL
ANATOMY
Most fat-soluble
substances such as vitamins are absorbed in the distal ileum
DIGESTION
& ABSORPTION
CARBOHYDRATES
Carbohydrate
absorption: requires breakdown to monosaccharides glucose, galactose,
and fructose
Pancreatic amylase:
primarily responsible for carbohydrate digestion
PROTEINS
Protein digestion:
begins in stomach, but quantitatively important digestion occurs in
small intestines
Peptides and amino
acids are cotransported into enterocytes with Na+
LIPIDS
Overview
Triglyceride
digestion: primarily occurs in small intestines
Digestion
Large lipid
droplets →
emulsification via bile and lecithin →
small lipid globules →
pancreatic lipase →
free fatty acids,and monoglycerides →
bile salts form micelles →
absorption
Absorption
Triglyceride
transport: occurs through chylomicrons, which drain from intestinal
lymphatics to thoracic duct to the left subclavian vein
ABSORPTION
OF OTHER SUBSTANCES
Sodium
Lumen-intracellular
Na+ gradient drives much of intestinal absorption, just as it does in
the proximal nephron
Vitamin
B12 (cobalamin)
Cobalamin is
absorbed in the distal ileum; diseases of distal ileum can impair its
absorption
Iron
(Fe)
Iron: abundant
in meats; absorbed in proximal small bowel, transported in blood bound
to transferrin; stored intracellularly as ferritin
MOTILITY
: MIGRATING MYOELECTRIC COMPLEX
Migrating
myoelectric complex: clears out intestinal tract during interdigestive
periods; hormone motilin plays important role
REFLEXES
Intestinal
reflexes: entirely contained within the enteric nervous system
Gastrocolic reflex: distension of the stomach promotes a bowel movement
Gastroileal reflex: promotes passage of intestinal contents from the
small intestine into the colon
Enterogastric reflex: entry of acidic chyme into duodenum inhibits
further gastric emptying
LARGE
INTESTINE
FUNCTIONAL
ANATOMY
Functions of colon:
salt and water reabsorption; elimination of feces
ELECTROLYTE
MOVEMENTS
DEFECATION
REFLEX
UNSORTED
-
DIGESTIVE
ABSORPTION
GASTRIC EPITHELIAL
TRANSPORT
NUTRITION
-
END
OF UNSORTED
TOC
ENDOCRINE & REPRODUCTIVE
OVERVIEW ENDOCRINE
HYPOTHALAMUS & PITUITARY
THYROID & PARATHYROID
ADRENAL GLAND
PANCREAS
OVERVIEW REPRODUCTIVE
GAMETOGENESIS
SPERMATOGENESIS
OOGENESIS
MENSTRUAL CYCLE AND OVULATION
GONADAL STEROIDS
SEXUAL RESPONSE
FERTILIZATION
PREGNANCY
MENOPAUSE
INTEGRATIVE SYSTEMS OF THE BODY
HORMONES
OVERVIEW
Hormones
maintain homeostasis by regulating processes such as development,
metabolism, and reproduction
Hormones:
maintain homeostasis through feedback loops
Hormones: act
slowly relative to nervous system
MECHANISM
OF ACTION OF HORMONES
Endocrinopathies:
due to qualitative or quantitative defect in hormone synthesis and/or
tissue sensitivity to hormone
TYPES OF HORMONES
& THEIR INDIVIDUAL EFFECTOR MECHANISMS
Steroid hormones: produced
continuously, cannot be stored, synthesis and secretion " on demand
Steroid hormones:
circulate bound to proteins, diffuse freely through cell membranes
Sex steroids:
testosterone, progesterone, estrogen
Adrenal steroids:
aldosterone, cortisol
Thyroid
hormones: derived from amino acid tyrosine, not cholesterol
Protein,
peptide, amino acid hormones: hydrophilic, stored in vesicles,
released on demand, bind membrane- bound receptors
Membrane-spanning
receptors: kinase receptors, ligand-gated ion channels, receptor- linked
kinases, G protein– coupled receptors
HORMONE-BINDING
PROTEINS
Hormone-binding
proteins: extend half-life of bound hormone, levels often ↑ in pregnancy
HIERARCHICAL
CONTROL OF HORMONE SECRETION
Hypothalamic-hypophyseal
portal
system: targets delivery of hypothalamic hormones to
adenohypophysis with minimal systemic distribution
Posterior
pituitary: composed of axonal extensions originating from hypothalamus
CLASSIFICATION OF
ENDOCRINE DISEASES
Location
of defect: primary disease: endocrine gland; secondary disease:
pituitary; tertiary disease: hypothalamus
HYPOTHALAMIC-PITUITARY
HORMONES / SYSTEM
ADH post
water permeability
of distal convoluted tubule and collecting duct cells in kidney to water
reabsorption
CRH
ACTH, MSH,
β-endorphin
Dopamine
prolactin, TSH
GHRH
GH
GnRH
FSH, LH
MSH
melanogenesis by
melanocytes
Oxytocin
post
Causes uterine
contractions during labor - Responsible for milk letdown reflex in
response to suckling
Prolactin
GnRH Stimulates lactogenesis
Somatostatin
GH, TSH
TRH
TSH, prolactin
HORMONAL
CONTROL SYSTEMS OF THE ANTERIOR PITUITARY
HYPOTHALAMIC-PITUITARY-ADRENAL AXIS
OVERVIEW
Androgens : do
not feedback-inhibit
ACTH secretion
Primary
glucocorticoid: cortisol
Primary androgen : DHEA
REGULATION
OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS
Cortisol
secretion : stimulated by physiologic stressors
Cortisol
secretion : diurnal pattern, highest in morning
BIOSYNTHETIC PATHWAY OF ADRENAL CORTICOSTEROIDS
Rate-limiting
step in steroid hormone synthesis: conversion of cholesterol to
pregnenolone
Layers
of adrenal cortex: “GFR” for zona glomerulosa, fasciculata, and
reticularis
Aldosterone
synthesis: regulated by K+ and angiotensin II rather than ACTH
MECHANISM OF ACTION OF CORTISOL
Steroid
hormones: regulate expression of genes containing steroid- responsive
elements
Steroid hormones: effects can take hours to days to manifest because they
work by altering gene expression
PHYSIOLOGIC ACTIONS OF CORTISOL
Metabolic
actions of cortisol: generally catabolic, stimulates gluconeogenesis,
preserves plasma glucose
Cortisol:
exerts mineralocorticoid effects at higher plasma concentrations
Cortisol:
potent anti-inflammatory but with myriad acute and chronic side effects
Cortisol: inhibits osteoblasts, stimulates osteoclasts
Avascular necrosis: steroids may precipitate; most commonly occurs in hip
Cortisol: inhibits intestinal Ca2+ absorption; inhibits calcitriol
synthesis
PATHOPHYSIOLOGY OF THE CRH-ACTH-CORTISOL AXIS
Hypercortisolism
(Cushing syndrome)
Manifestations of chronic hypercortisolism:
diabetes mellitus, muscle atrophy, osteoporosis, hypertension
Cushing syndrome: most often iatrogenic
Pituitary Cushing: most common pathologic cause of Cushing syndrome;
caused by ACTH- hypersecreting pituitary adenoma
Pituitary
Cushing: ACTH should partially suppress in response to high-dose
dexamethasone; ectopic and adrenal Cushing do not suppress
Hypocortisolism
(adrenal insufficiency)
Symptoms
of adrenal insufficiency: nonspecific and vague, include fatigue,
nausea, abdominal pain, and diarrhea
Adrenal
insufficiency: most commonly iatrogenic from chronic administration of
steroids
Primary adrenal
insufficiency: ↑ ACTH, hyperpigmentation; secondary adrenal
insufficiency: ↓ ACTH, no hyperpigmentation
HYPOTHALAMIC-PITUITARY REGULATION OF ADRENAL ANDROGEN SYNTHESIS
ACTH:
stimulates adrenal androgen synthesis
Androgens: do not feedback-inhibit ACTH secretion
PATHOPHYSIOLOGY OF CONGENITAL ADRENAL HYPERPLASIAS (CAH)
Congenital
adrenal hyperplasias: relatively rare disorders characterized by enzyme
defects in cortisol biosynthetic pathway
CAH: ↑ ACTH →
adrenal
hyperplasia → ↑ shunting of
cortisol precursors to androgens
21-hydroxylase deficiency: most common cause of CAH 11beta-hydroxylase
deficiency: rare
Congenital adrenal hyperplasias: precocious puberty in male children,
ambiguous genitalia in female neonates
Most common causes of CAH: 21-hydroxylase deficiency; salt wasting,
hypotension
PATHOPHYSIOLOGY OF ADRENAL DISORDER
HYPOTHALAMIC-PITUITARY-THYROID AXIS
OVERVIEW
TRH
→ TSH → T3 + T4 → physiologic actions
Calcitonin :
secreted by parafollicular cells, involved in Ca2+ regulation; not
regulated by hypothalamic-pituitary- thyroid axis
STEPS IN THE SYNTHESIS OF THYROID HORMONES
Thyroglobulin: primary
protein of follicular lumen; substrate on which thyroid hormones are
produced
Plasma
thyroglobulin: levels can be used to detect and monitor certain types of
thyroid cancer
Thionamides:
inhibit the organification step
Colloid: large
storage depot for thyroid hormones
Amiodarone:
can cause both hypothyroidism and hyperthyroidism
PHYSIOLOGIC ACTIONS OF THYROID HORMONES
Thyroid
hormones: up-regulate expression of Na+,K+-ATPase pump
Thyroid
hormones: excessive levels → enhanced sensitivity to circulating
catecholamines → palpitations, tremors; symptoms may respond to
beta-blockers
DIFFERENCES BETWEEN T4 & T3
Thyroxine (T4):
basically a prohormone; T3 much more active
T4: much more
abundant than T3 so primarily responsible for feedback inhibition of
pituitary
PATHOPHYSIOLOGY
Hyperthyroidism
Hyperthyroidism:
refers only to a pathologic increase in synthesis of thyroid hormone
Thyrotoxicosis:
symptomatology
associated with pathologically elevated levels of
thyroid hormones irrespective of the etiology (e.g., gland
destruction; increased synthesis)
Manifestations
of
hyperthyroidism: include weight loss with increased appetite, heat
intolerance,diarrhea, and often atrial fibrillation
Graves
disease: most common cause of hyperthyroidism
Graves disease: IgG antibodies mimic TSH and stimulate TSH receptor on
thyroid
TSH-secreting pituitary tumor: rare cause of hyperthyroidism
TRH-secreting hypothalamic tumor: very rare cause of hyperthyroidism
Thyroiditis:
release of preformed thyroid hormone → transient thyrotoxicosis
Hypothyroidism
Manifestations
of
hypothyroidism: weight gain, cold intolerance, bradycardia, atrial
fibrillation, dulled mentation, short stature
Congenital hypothyroidism: may cause cretinism
Euthyroid sick syndrome
Euthyroid
sick
syndrome: low to normal T3 and T4 in ill patients with no apparent
signs of thyroid dysfunction; very common in hospitalized patients
Reverse
T3 (rT3): binds T3 receptor, blocking normal T3 from binding
HYPOTHALAMIC-PITUITARY-GONADAL AXIS
MALE REPRODUCTIVE AXIS
MECHANISM OF ACTION OF TESTOSTERONE
Testosterone:
converted to more potent form (DHT) by 5alpha-reductase in certain tissues
such as skin and prostate
PHYSIOLOGIC ACTIONS OF TESTOSTERONE & DIHYDROTESTOSTERONE (DHT)
Testosterone:
responsible for development of seminal vesicles, epididymis, vas deferens
during embryogenesis
Absent testosterone: female sex organs will develop even in genetically
male fetus
Testosterone:
↑ lean muscle mass, bone density
DHT: responsible
for male pattern baldness in genetically prone men
Testosterone:
responsible for the development of lean muscle mass, deepening of voice
in men
REGULATION OF TESTOSTERONE SECRETION
Leuprolide:
synthetic
GnRH agonist given in nonpulsatile manner; cessation of
menses in woman; ↓ androgen production in men with prostate cancer
PUBERTY IN MALES
SPERMATOGENESIS
Spermatogenesis:
process of sperm maturation in which a haploid male gamete is produced
FEMALE REPRODUCTIVE AXIS
PHYSIOLOGIC ACTIONS OF ESTROGEN
Estrogen
and progesterone: unnecessary for development of female primary sex organs
Estrogen: responsible for development of female secondary sexual
characteristics (e.g., breast maturation, fat deposition on hips and
buttocks)
PHYSIOLOGIC ACTIONS OF PROGESTERONE
Actions
of progesterone: breast development, regulation of menstrual cycle,
maintenance of pregnancy
REGULATION OF SECRETION OF ESTROGEN AND PROGESTERONE
Estrogen
and progesterone: antagonize effects of prolactin → prevent milk letdown
in pregnant women
FSH
stimulates estrogen synthesis
by granulosa cells
LH
stimulates progesterone
synthesis by theca cells
MENSTRUAL CYCLE
Dominant
follicle: ultimately emerges, and remaining follicles undergo atresia
Dominant follicle: becomes increasingly sensitive to FSH → ↑ estrogen
levels → switch from negative to positive feedback on pituitary → LH
and FSH surge
LH surge: causes ovulation
Corpus
luteum: composed of cells lining dominant ovarian follicle; secretes
estrogen and progesterone
Corpus luteum: if ovum not fertilized, corpus luteum degenerates; if
fertilized, corpus luteum maintained by hCG secretion from embryo
Follicular phase: time between first day of menses and ovulation; since
luteal phase fixed, differences in length of this phase account for
cycle length differences
Luteal
phase: secretory phase; period between ovulation and menses
Menses:
sloughing off of endometrial lining, triggered by drop in estrogen and
progesterone
PATHOPHYSIOLOGY OF REPRODUCTIVE DISORDERS
PROLACTIN
PHYSIOLOGIC ACTIONS
Prolactin:
promotes breast maturation and lactogenesis in pregnant females
Lactation during pregnancy: despite high prolactin levels, is inhibited by
high levels of estrogen and progesterone
Hyperprolactinemia with breastfeeding: serves as natural (but imperfect!)
contraceptive by inhibiting GnRH secretion
PROLACTIN SECRETION
Prolactin
secretion: stimulated by breastfeeding, excessive nipple stimulation,
typical antipsychotics, hypothyroidism, severing of the pituitary stalk
Prolactin
secretion: inhibited by dopamine agonists such as bromocriptine; used in
treatment of pituitary prolactinomas
PATHOPHYSIOLOGY
Hyperprolactinemia in
nonpregnant women: galactorrhea, anovulatory infertility
Hyperprolactinemia
in men: hard to diagnose; may cause depression and ↓ libido
GROWTH HORMONE (GH)
ANABOLIC ACTIONS
GH
actions: anabolic; primarily mediated through IGF-1
METABOLIC ACTIONS
GH/IGF-1:
stimulates
lipolysis, inhibits peripheral utilization of glucose,
stimulates gluconeogenesis to preserve plasma glucose
GH/IGF-1: preserves skeletal protein in an attempt to maintain ability of
organism to “hunt and gather” during starvation
GH: diabetogenic hormone; chronically excessive levels → diabetes
GH deficiency: intentional provocation of hypoglycemia should ↑ GH
secretion if hypothalamic-pituitary axis functioning normally
REGULATION OF SECRETION
GH
secretion: stimulated by sleep, stress, hypoglycemia; inhibited by alcohol
HORMONAL CONTROL SYSTEMS OF THE POSTERIOR PITUITARY
OVERVIEW
Posterior
pituitary: composed of axonal extension from hypothalamus;
independent of hypothalamic releasing hormones, which only influence the
anterior pituitary
HORMONES OF THE POSTERIOR PITUITARY
ANTIDIURETIC HORMONE (ADH, ARGININE VASOPRESSIN, VASOPRESSIN)
PHYSIOLOGIC ACTIONS
ADH
:
stimulates (1) free water reabsorption and (2) systemic
vasoconstriction → maintains plasma osmolarity and ↑ blood pressure
ADH SECRETION
ADH
secretion: triggered by ↑ plasma osmolarity and ↓ plasma volume
PATHOPHYSIOLOGY OF DIABETES INSIPIDUS (DI)
Central diabetes insipidus: common
with head trauma; urine should concentrate following administration of
synthetic ADH
Nephrogenic diabetes insipidus:
commonly caused by lithium; urine will not
concentrate with synthetic ADH
PATHOPHYSIOLOGY OF THE SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE
SECRETION (SIADH)
SIADH:
common in hospitalized patients; triggered by pain, medications, lung
infections and tumors
OXYTOCIN
Oxytocin:
promotes uterine contractions and milk letdown
HORMONAL CONTROL SYSTEMS INDEPENDENT OF PITUITARY REGULATION
ENDOCRINE PANCREAS &
CARBOHYDRATE METABOLISM
Islets of
Langerhans: beta cells secrete insulin; alpha cells secrete glucagon;
delta cells secrete somatostatin
INSULIN
MECHANISM OF ACTION
Insulin:
stimulates glucose uptake in various tissues
METABOLIC ACTIONS
Insulin:
promotes glucose use in multiple ways; stimulates glycolysis,
glycogenesis, and glucose uptake in adipose and muscle
Insulin-independent
tissues:
CNS is mainly dependent on glucose as fuel source, does not
need insulin to internalize glucose, allowing the CNS to function
at low glucose levels when plasma [insulin] is low
PATHOPHYSIOLOGY OF TYPE 1 DIABETES MELLITUS
Type
1 diabetes mellitus: caused by autoimmune and antibody destruction of
pancreatic beta cells
Hyperglycemia:
filtered
load of glucose exceeds renal capacity for glucose
reabsorption, resulting in glucosuria and osmotic diuresis
Classic
presentation
of diabetes mellitus: polydipsia, polyuria, and
unintentional weight loss with a preserved or increased appetite
(polyphagia)
DIABETIC KETOACIDOSIS
DKA:
absolute deficiency in insulin; anion gap metabolic acidosis,
hyperglycemia, volume depletion
DKA: often triggered by noncompliance with insulin or by infections
PATHOPHYSIOLOGY OF TYPE 2 DIABETES MELLITUS
Type
2 diabetes mellitus: insulin levels initially elevated but still
inadequate because of target tissue insensitivity to insulin from
decreased receptors and postreceptor abnormalities
Type 2 diabetes mellitus: beta-cell dysfunction with impaired insulin
secretion plays a larger role in later stages of diabetes
HHS : characterized by marked volume depletion, much more so than with
DKA, and a much more elevated [glucose]; absent ketogenesis results
from the presence of some insulin
GLUCAGON
PRIMARY HORMONE OF THE FASTING STATE
REGULATION OF SECRETION
Glucagon
secretion: stimulated by amino acids and low plasma glucose
PHYSIOLOGIC ACTIONS
Glucagon:
acts
primarily on liver to promote gluconeogenesis and glycogenolysis;
weakly stimulates lipolysis in adipose tissue; inhibits glucose
utilization by peripheral tissues
ADRENAL MINERALOCORTICOIDS
PHYSIOLOGIC ACTIONS OF ALDOSTERONE
Aldosterone:
acts to maintain blood pressure by increasing intravascular volume
Hyperaldosteronism: moderate common cause of secondary hypertension,
hypokalemia, and metabolic alkalosis
REGULATION OF ALDOSTERONE SECRETION
Aldosterone
secretion: regulated by K+ and angiotensin II, minimal effect by ACTH
ADRENAL CATECHOLAMINES
OVERVIEW
Adrenal
catecholamines: epinephrine, norepinephrine, and dopamine
Epinephrine:
secreted by medulla in larger amounts than epinephrine or dopamine
PHYSIOLOGIC ACTIONS OF CATECHOLAMINES
Catecholamines:
↑
heart rate and contractility, ↑ total peripheral resistance by
stimulating arterial vasoconstriction, stimulate bronchodilation
Metabolic
actions of catecholamines: maintain plasma glucose by stimulating
hepatic glycogenolysis and gluconeogenesis and lipolysis in adipose
tissue
REGULATION OF SECRETION OF EPINEPHRINE
Epinephrine
secretion: primarily under control of autonomic nervous system
CALCIUM & PHOSPHATE HOMEOSTASIS : PARATHYROID HORMONE (PTH), VITAMIN
D, & CALCITONIN - &
MAGNESIUM METABOLISM
CALCIUM
HOMEOSTASIS
Plasma Ca2+ exists in three forms Ionized/free (~ 45%,
active form)
Bound to albumin (∼ 40%)
Bound to anions (∼ 15%)
Calcium:
approximately 99% is located in the bones
Calcium
regulation : dependent on PTH,
calcitriol, and (minimally) calcitonin
Calcium regulation:
it is the ionized calcium that
is tightly regulated
Alkalosis: ↓
ionized Ca2+ as a result of ↑ Ca2+ binding to negatively charged sites
on albumin
Ionized / free Ca2+
is 1° regulator of PTH ;
changes in pH alter PTH secretion,
whereas
changes in albumin concentration do not
Ca2+ competes with
H+ to bind to albumin
↑
pH
(less H+) →
albumin
binds more
Ca2+ → ↓ ionized
Ca2+ (eg, cramps, pain,
paresthesias, carpopedal spasm) → ↑ PTH
↓ pH (more
H+) → albumin
binds less Ca2+
→ ↑ ionized
Ca2+ → ↓ PTH
Calcium:
stabilizes membrane potentials ; hypocalcemia
→ muscle spasms (tetany), cardiac arrhythmias, and seizures
Manifestations of hypercalcemia: confusion, muscle
weakness, osmotic diuresis → dehydration and possibly (prerenal) renal
failure
PARATHYROID
HORMONE
PTH : secreted by
parathyroid chief cells primarily in response to hypocalcemia
but also to hyperphosphatemia
1,25-DIHYDROXYVITAMIN
D3
Vitamin D from diet
or skin →
25-hydroxyvitamin D (liver) →
1,25- dihydroxyvitamin D3 (kidney)
PHOSPHATE
HOMEOSTASIS
Metastatic
calcification: can occur when the calcium-phosphate product level is
pathologically elevated
1,25-Dihydroxyvitamin
D3:
stimulates intestinal absorption of calcium and phosphate; also
stimulates renal reabsorption of phosphate
UNSORTED
HUMORAL SIGNALS : CONTROL & EFFECTS
INTRACELLULAR TRANSMISSION OF SIGNALS FROM EXTRACELLULAR MESSENGERS
ADRENAL CORTEX & GLUCOCORTICOIDS
OOGENESIS & THE MENSTRUAL CYCLE
HORMONAL CONTROL OF THE MENSTRUAL CYCLE
ESTROGENS, PROGESTERONE
HORMONAL CONTROL OF PREGNANCY & BIRTH
ANDROGENS & TESTICULAR FUNCTION
SEXUAL RESPONSE, INTERCOURSE & FERTILIZATION
ADIPOSE
TISSUE & OBESITY
METABOLISM
& REGULATION
NEUROENDOCRINOLOGY
MATERNAL,
FETAL & NEONATAL PHYSIOLOGY
ADRENAL STEROIDS & CONGENITAL ADRENAL HYPERPLASIAS
APPETITE REGULATION
SIGNALING PATHWAYS OF ENDOCRINE HORMONES
SIGNALING PATHWAYS OF STEROID HORMONES
TOC
REPRODUCTION
TOC
ACID BASE BALANCE
CONTENTS
OVERVIEW
Darrow
Yannet diagram - Base excess - Davenport diagram - Anion gap (Delta ratio)
- Winters' formula - Buffering
(Bicarbonate buffer system - Respiratory compensation - Renal
compensation)
ACIDS, BASES, & BUFFERS
LINES OF DEFENSE
Chemical - immediate
bicarbonate
buffer system, the phosphate buffer system, and the protein buffer system
Respiratory component - rapid
control
the carbonic acid (H2CO3) concentration in the ECF
Metabolic component - mostly renal - slow - ROLE OF THE KIDNEYS IN
ACID-BASE BALANCE
measured by the
base excess
add
or remove bicarbonate ions (HCO−3) to or from the ECF
BALANCE
HENDERSON–HASSELBALCH
EQUATION
HOMEOSTATIC MECHANISMS
IMBALANCE
METABOLIC ACIDOSIS
High
anion gap (Ketoacidosis - Diabetic ketoacidosis - Alcoholic
ketoacidosis - Lactic)
Normal anion gap (Hyperchloremic - Renal
tubular)
METABOLIC ALKALOSIS
(contraction)
RESPIRATORY ACIDOSIS
RESPIRATORY ALKALOSIS
MIXED
-
PH, PH BUFFERS, ACID-BASE BALANCE
BICARBONATE/CARBON DIOXIDE BUFFER
ACIDOSIS AND ALKALOSIS
ASSESSMENT OF ACID-BASE STATUS
-
END OF CONTENTS
OVERVIEW
pH
maintained in tight range to preserve protein function
Tight
control of pH: maintained by buffers, removal of CO2 by lungs, excretion
of nonvolatile acids by kidneys
Metabolism
of fats and carbohydrates to CO2 produces an enormous daily acid load;
most of this can be removed by the lungs
Metabolism of proteins to nonvolatile acids produces a modest daily
acid load; most of this is excreted by the kidneys
Primary buffer of ECF: bicarbonate system
Primary nonvolatile acids removed by kidneys: sulfate, phosphate
Diagnosis of acid-base disorder: often inferred from electrolyte
abnormalities alone if clinical story highly suggestive
Acidemia: low plasma pH; acidosis: process in which excess acid is
produced
Alkalemia: high plasma pH; alkalosis: process in which excess base is
produced
Normal pH does not mean an underlying acid-base disturbance is not present
ACIDS, BASES, & BUFFERS
H2CO3: weak acid; HCO3-: its conjugate base
pKa:
pH at which acid is half dissociated
HCO3-/CO2 system
most important buffer in the plasma
Buffering
systems typically work best at a pH near their pKa; the bicarbonate
system is an exception because of the ability of CO2 and HCO3- to be
rapidly removed by the lungs and kidneys, respectively
ROLE OF THE KIDNEYS IN ACID-BASE BALANCE
OVERVIEW
Ammoniagenesis:
process whereby HCO3- is produced and NH4+ is excreted in urine
BICARBONATE RECLAMATION
Bicarbonate
reclamation: no net acid secretion or generation
DE NOVO BICARBONATE SYNTHESIS
Urinary
buffers: maximize acid excretory capacity of the kidneys
Titratable acidity
Filtered phosphate (HPO4 -2): major contributor to titratable acidity
Ammonium production
Deamination of glutamine: produces two NH4+ molecules and two HCO3-
molecules
Regulation of de novo bicarbonate
synthesis
HCO3- reclamation: normally approximates 100%
As systemic pH falls → ↑ H+
excretion by kidneys
As systemic pH increases → ↓ H+
excretion by kidneys
METABOLIC ACIDOSIS
OVERVIEW
Causes of
metabolic acidosis : excess acid production, impaired renal acid excretion
Metabolic
acidosis: low pH, low [HCO3-], low PCO2
Metabolic
acidoses: classified as anion gap or normal anion gap
Anion
gap acidoses: typically clinically serious conditions requiring emergent
therapy
Normal
gap acidoses: renal and extrarenal etiologies
Renal
causes of normal anion gap acidosis: early acute renal failure, renal
tubular acidoses
Extrarenal
causes of normal anion gap acidosis: diarrhea, dilutional,
ureteral-colonic fistulas
Anion
gap: measured by subtracting measured anions from measured cations
AG = Na+ - (Cl- +
HCO3); normal anion gap is ~12
Anion
gap acidosis: results from consumption of HCO3- by buffering H+ ions and
production of unmeasured anions
UAG:
can help differentiate renal and extrarenal causes of normal AG metabolic
acidosis
A
negative UAG in a setting of a normal anion gap metabolic acidosis
indicates an extrarenal etiology for the acidosis
If
the UAG is positive, RTA is likely
To
determine type of RTA: examine urine pH, serum pH, serum [K+], and the
fractional excretion of HCO3- after a bicarbonate load
RESPIRATORY COMPENSATION
Respiratory
compensation for metabolic acidosis: hyperventilation to “blow off” CO2
Winter’s
formula: PCO2 = 1.5 x [HCO3-] + 8 ++- 2
Respiratory
compensation for metabolic acidosis: PCO2 should drop by 1.2 mm Hg for
each 1 mEq/L drop in [HCO3-]
CAUSES OF ANION-GAP METABOLIC ACIDOSIS
Renal failure
Pathophysiology
of
renal failure causing metabolic acidosis: due to too few functional
nephrons and decreased glomerular filtration rate rather than specific
acid secretory defect
Acute
renal failure: can cause an anion gap or a normal anion gap metabolic
acidosis
Lactic acidosis
Lactic
acidosis: generally caused by diffuse tissue hypoperfusion
Lactic
acidosis: seen in shock, sepsis, prolonged seizures, prolonged strenuous
exercise
Diabetic ketoacidosis (DKA)
DKA:
typically occurs in patients with type 1 diabetes, often as their initial
presentation
DKA: characterized by hyperglycemia, volume depletion, ketosis, anion gap
acidosis
DKA: caused by an absolute deficiency in insulin
Pathogenesis of DKA: runaway lipolysis supplies ketogenic precursors to
the liver, resulting in ketogenesis and acidosis
Hyperglycemia in DKA: causes dehydration through osmotic diuresis; reduced
GFR further impairs acid excretory ability of kidneys
Hyperkalemia: may be present despite total body potassium wasting
Causes of hyperkalemia in DKA: solvent-drag effect, buffering role,
insulin deficiency
Acetylsalicylic (aspirin) toxicity
Anion
gap acidosis + respiratory alkalosis +- tinnitus → think aspirin intoxication
Reye syndrome in children: ingestion of aspirin in setting of viral
illness → liver failure,
encephalopathy, hypoglycemia
Aspirin toxicity: causes respiratory alkalosis and anion gap metabolic
acidosis
Methanol ingestion
Anion
gap acidosis + blurry vision → think methanol
ingestion
Ethanol and fomepizole: competitively inhibit alcohol dehydrogenase → ↓ formic acid
production → minimize toxic
effects
Ethylene glycol toxicity
Ethylene
glycol: sweet- tasting substance present in antifreeze
Anion gap acidosis +
urine with oxalate crystals and/or Woods lamp fluorescence → think ethylene glycol ingestion
CAUSES OF NORMAL ANION GAP METABOLIC ACIDOSIS
Diarrhea
Diarrhea:
most common cause of normal anion gap acidosis
Chronic
diarrhea: may cause a metabolic alkalosis because of volume contraction
Renal tubular acidosis
METABOLIC ALKALOSIS
OVERVIEW
Metabolic alkalosis: high HCO3-, high pH, and high PCO2
Metabolic alkalosis: think volume-depleted states (e.g., vomiting) or hyperreninemic and/or hyperaldosteronemic states
Respiratory compensation for metabolic alkalosis: hypoventilatory capacity limited owing to resulting hypoxemia
SPECIFIC CAUSES OF METABOLIC ALKALOSIS
Vomiting
Vomiting: powerfully stimulates metabolic alkalosis through direct loss of H+, loss of Cl-, and volume depletion
Mineralocorticoid excess
Mineralocorticoid excess: think volume expansion, hypertension, hypokalemia, hypernatremia, metabolic alkalosis
Excess
mineralocorticoid- like states: Conn syndrome, Cushing syndrome,
Bartter syndrome, Gitelman syndrome, Liddle disease, 11b-(OH)-steroid
dehydrogenase deficiency, licorice ingestion
RESPIRATORY COMPENSATION
Respiratory compensation for metabolic alkalosis: hypoventilation → ↑ PCO2
Expected rise in PCO2: 0.7 mm Hg for every 1 mEq/L rise in [HCO3-]
RESPIRATORY ACIDOSIS
OVERVIEW
Respiratory acidosis: almost always caused by alveolar hypoventilation
Respiratory acidosis: may cause CO2 narcosis, ↑ ICP, cardiac dysrhythmias, impaired cardiac contractility, hypoxemia
Hypoventilation as a compensatory response to metabolic alkalosis will not cause hypoxemia
Therapy for respiratory acidosis: may involve mechanical intubation
SPECIFIC CAUSES OF RESPIRATORY ACIDOSIS
METABOLIC COMPENSATION
Acute compensation for respiratory acidosis: ↑ in [HCO3-] by 1 mEq/L for every 10 mm Hg rise in PCO2
Renal compensation: maximally effective within 3 to 5 days
Chronic compensation: ↑ in [HCO3-] by 3.5 mEq/L for every 10 mm Hg rise in PCO2
RESPIRATORY ALKALOSIS
OVERVIEW
Respiratory alkalosis: always caused by alveolar hyperventilation
Respiratory alkalosis: occurs in response to hypoxemia and/or central causes
Respiratory alkalosis: PCO2, high pH, and low HCO3-
Kidneys better able to compensate for respiratory alkalosis than for respiratory acidosis
SPECIFIC CAUSES OF RESPIRATORY ALKALOSIS
METABOLIC COMPENSATION
Acute compensation
Intracellular shift of H+ ions: due to “release” of H+ ions from intracellular proteins, hemoglobin, phosphate
Acute compensation for respiratory alkalosis: ↓ [HCO3-] by 2 mEq/L for every 10 mm Hg ↓ in PCO2
Chronic compensation
Chronic compensation for respiratory alkalosis: ↓ [HCO3-] by 4 mEq/L for every 10 mm Hg ↓ in PCO2
TOC
SODIUM
& WATER BALANCE,
FLUID COMPARTIMENTS
CONTENTS
BODY FLUIDS
DISTRIBUTION OF BODY FLUIDS
MEASUREMENT OF FLUID COMPARTMENTS
REGULATION OF SODIUM & WATER BALANCE
GENERAL PRINCIPLES
EFFECTIVE CIRCULATORY
VOLUME
END OF CONTENTS
BODY
FLUIDS
DISTRIBUTION OF BODY FLUIDS
FLUID COMPARTMENTS
TBW: ~50% (women) to 60% (men) of body weight
Approximately two thirds of TBW is ICF, one third ECF
ECF: composed of IF, plasma, transcellular fluids
In disease states such as ascites or pleural effusion the transcellular compartment can increase substantially
COMPOSITION OF FLUID COMPARTMENTS
INTRACELLULAR FLUID
ICF rich in protein, potassium, calcium, and phosphate
K+: major ICF cation
Intracellular phosphate: important in ATP synthesis and intracellular buffering
EXTRACELLULAR FLUID
ECF rich in sodium, chloride; low in potassium and phosphate
Interstitial fluid
IF protein poor; excess fluid and proteins returned to vascular compartment through lymphatics
Dysfunction or obstruction of lymphatic drainage may result in interstitial edema
Plasma
MEASUREMENT OF FLUID COMPARTMENTS
Indicator substance: diffusion-restricted to specific fluid compartment
Deuterium and tritiated water: measure TBW volume
Inulin and mannitol: measure ECF volume
Radiolabeled albumin: measure plasma volume
REGULATION OF SODIUM & WATER BALANCE
GENERAL PRINCIPLES
Volume : regulated through sodium balance
Osmolarity and sodium concentration : regulated through water balance
Kidneys regulate ECF volume by adjusting Na+ excretion
ECV osmolarity and Na+ concentration regulated through water balance via ADH secretion
Hyponatremia (in presence of normal ECV) inhibits ADH secretion
Hypernatremia stimulates ADH secretion
EFFECTIVE CIRCULATORY
VOLUME
ECV: portion of intravascular compartment perfusing organs
ECV: varies with ECF volume and total body sodium
Pressure and volume detectors monitor ECF volume
RESPONSE TO DECREASE IN EFFECTIVE CIRCULATING VOLUME
ECV: sensed by stretch receptors in carotid sinus, aortic arch, and glomerular afferent artery
Sympathetic outflow with ↓ ECV: multiple actions to ↑ plasma volume, retain sodium, and ↑ arterial perfusion pressure
Diarrhea: isosmotic volume contraction
Water deprivation: hyperosmotic volume contraction
Adrenal insufficiency: hyposmotic volume contraction
RESPONSE TO INCREASED EFFECTIVE CIRCULATING VOLUME
Response to ↑ ECV: ↑ baroreceptor stretch → ↓ sympathetic outflow → ↓ CO and blood pressure
Saline infusion: isosmotic volume expansion
↑ NaCl intake: hyperosmolar volume expansion
SIADH: hyposmotic volume expansion
TOC
NEUROPSYCHOPHYSIOLOGY &
NEUROSCIENCE
OVERVIEW
(Baillet 46
Du modèle du cerveau triunitaire à une neuropsychophysiologie humaine des
affects et de la cognition Sommaire) V1 JPG & V1 PDF
(Baillet 47
Vascularisation du névraxe, liquide cephalo-rachidien et barrière
hemato-encephalique Sommaire) V1 JPG
(Baillet
48
Microcomposants du systeme nerveux central Sommaire) V1 JPG
(Baillet
49 Métamere médullaire : système réflexe et programmation du mouvement Sommaire) V1 JPG
(Baillet
50 Organisation générale du cortex I Sommaire)
V1 JPG
(Baillet
51 Système Axial = Bas (Tronc Cérébral) & Haut (Hypothalamus) Sommaire) V1 JPG
(Baillet
52 Système limbique & projections axiofuges corticotropes
extrathalamiques modulatrices Sommaire)
V1 JPG
(Baillet
53 Afferences affectives Sommaire)
V1 JPG
(Baillet
54 Cortex II : Afferences Cognitives Sommaire)
V1 JPG
(Baillet
55 Thalamus
& Noyaux
gris centraux Sommaire)
V1 JPG
(Baillet
56 Cervelet, intégration et modulation de la motricité Sommaire) V1 JPG
(Baillet
57 Contrôle de la statique et de la visuomotricité Sommaire)
V1 JPG
(Baillet
58 Cortex moteur III : élaboration du mouvement Sommaire)
V1 JPG
(Baillet
59 Instinct, apprentissage, mémoire Sommaire)
V1 JPG
(Baillet
60 Comportement d'ingestion : la soif et la faim Sommaire)
V1 JPG
(Baillet
61 Neuroendocrinologie sexuelle mâle et femelle (chez l'adulte) Sommaire) V1 JPG
(Baillet
62 Fonction sexuelle Sommaire)
V1 JPG
(Baillet
63 Cortex IV : aires d'association et asymétrie inter-hémisphérique Sommaire) V1 JPG
(Baillet
64 Modulation de la vigilance et de l'humeur Sommaire)
V1 JPG
(Baillet
65 Rencontres (stress - émotion - prises de risque et de décisions) Sommaire) V1 JPG
(Baillet
"66" Epilogue : du modèle animal a des logiciels humains Sommaire) V1 JPG
(Krebs LIR
2017 Contents) V2 PDF
(Krebs LIR
2017 1 Intro to NS : cellular components & basic neurophysiology)
V1 PDF
Nervous system: allows one to think, move, feel, experience, and
manipulate one’s environment
ORGANIZATION
& FUNCTIONAL ANATOMY OF THE NERVOUS SYSTEM
CNS : comprises the brain and spinal cord
Nervous system : anatomically divided into CNS and PNS
PNS : functionally divided into somatic and autonomic components
Somatic nervous system : controls voluntary actions
Somatic nervous system : comprises afferent and efferent loops; requires
conscious processing
Autonomic nervous system : controls involuntary actions; active at
subconscious level
ANS comprises sensory and motor loops between visceral organs and CNS
ANS : subdivided into parasympathetic, sympathetic, and entericnnervous
systems
TOC
CELLS
NEURONS
ANATOMY
Cell
Body (Soma)
Dendrites
Axon
axon hillock myelin
nodes of Ranvier
Presynaptic
- Nerve -Terminals
EXCITABILITY
Action
potentials
Axon
diameter
Insulation
Saltatory
conduction
CLASSIFICATION
Pseudounipolar
Bipolar
Multipolar
TYPES
OF SYNAPSES
Axodendritic
synapses
Axosomatlc
synapses:
Axoaxonlc
synapses
NEURONS
AS INTEGRATORS
Incoming
signals
Filtering
Integration
Output
Encoding
NEUROTRANSMISSION
Neurotransmitters
Synaptic
vesicles
Release
Receptors
Signal
termination
GLIAL
CELLS
Astrocytes
Oligodendrocytes
Schwann calls
Microglial
cells
Polydendrocytes
Ependymal
cells
Myelination
Potassium homeostasis
Neurotransmitter
uptake and recycling
Nutrient
supply
PROTECTION OF THE BRAIN
Protection
of the brain: ensured by blood-brain barrier and blood-CSF barrier
BLOOD-BRAIN BARRIER BBB
BBB:
endothelial cells connected by tight junctions with underlying basement
membrane and surrounding astrocytes
BBB:
lipid-soluble substances cross easily
BBB: active transport systems in place for substances such as organic
acids and K+ ions
Parts of brain outside BBB: pineal gland, chemoreceptor trigger zone
BLOOD-CSF BARRIER
Blood-CSF
barrier: comprises highly vascular choroid plexus epithelial cells
connected by tight junctions
BASIC NEUROPHYSIOLOGY
ION MOVEMENTS
ACTION POTENTLAL
SYNAPTIC TRANSMISSION
NEUROTRANSMITTERS
TOC
CENTRAL
(Krebs LIR
2017
2 Overview Central)
V1 PDF
DEVELOPMENT
BRAIN
SPINAL
CORD
VENTRICULAR
SYSTEM
MENINGEAL
COVERINGS
CEREBRAL
BLOOD SUPPLY
Brain
is vulnerable to ischemia as a result of high metabolic rate and
dependence on glucose as fuel source
Internal carotid
arteries: >70% stenosis in the setting of an acute cerebrovascular
accident → indication for carotid
end arterectomy
Circle of Willis:
interconnects the internal carotid and vertebrobasilar systems to ensure
adequate cerebral perfusion
A stroke involving
the anterior cerebral artery may present as contralateral lower
extremity weakness
Cerebrovascular
accident involving proximal MCA and lenticulostriate branches may cause
contralateral arm weakness and dysarthria
Cerebrovascular
accident of distal left MCA can cause cortical deficits such as aphasia
Thrombosis of the
vertebral artery can cause severe brainstem ischemia and may result in
the so-called locked-in syndrome
TOC
PERIPHERAL
(Krebs LIR 2017 3 Overview
Peripheral
)
V1 PDF
PERIPHERAL
NERVE
Organization
Classlflcatlon
of fibers
SPINAL
NERVES
There
are 31 pairs of spinal nerves: 8 cervical, 12 thoracic, 5 lumbar, 5
sacral, 1 coccygeal
Nerves C1–C7 exit above the corresponding vertebrae
(eg, C3 exits above the 3rd cervical vertebra)
C8 spinal nerve
exits below C7 and above
T1
All other nerves exit below
(eg, L2 exits below the
2nd lumbar vertebra)
SENSORY
RECEPTORS
EFFECTOR
ENDINGS
Motor
unit
Neuromuscular
Junction
TOC
VISCERAL / AUTONOMIC
(Costanzo BRS) V1 PDF
(Krebs
LIR
2017 Visceral 4 )
V1 PDF
(Kamina Neuroanatomie & Dudek HY Anatomy)
V2 PDF
ORGANIZATION
SENSORY
: PAIN & PHYSIOLOGICAL FUNCTIONS
REFLEXES : REGULATION
RECEPTORS
CONTENTS
(Baillet 7 Synapses du
système nerveux végétatif Sommaire) V1 JPG
(Baillet 12
Organisation du système nerveux végétatif Sommaire) V1 JPG
OVERVIEW
blood
pressure (baroreceptors), blood chemistry (chemoreceptors), and body
temperature (thermoreceptors)
somatic
nervous system is a voluntary
autonomic nervous
system is an involuntary
HOMEOSTASIS
Mechanisms
Redundancy
Functional reserve
ORGANIZATION
& GENERAL FEATURES OF THE AUTONOMIC NERVOUS SYSTEM
smooth
muscle, cardiac muscle, & glands
TERMINOLOGY
3 divisions : sympathetic
parasympathetic enteric
Neurotransmitters
Adrenergic NE norepinephrine adreno-receptors
Cholinergic Ach cholino-receptors
non-adrenergic, non-cholinergic
NEUROEFFECTOR
JUNCTIONS OF THE AUTONOMIC NERVOUS SYSTEM
diffuse
varicosities
VISCEROSENSORY
related
to pain
anterolateral
- system Insular cortex - visceral pain
splnoretlcular fibers
related
to physiological functions
pelvic
nerves & CNs - anterior root - bladder rectum & fullness -
genital sensations & visceral reflex pathways
anterolateral
system - spinoreticular system
thoracic
& abdomlnal viscera - vagus nerve (CN X) - mechanoreceptors -
fullness & cramps
CN
IX, glonopharyngeal nerve- - viscera! afferent -
chemoreceptors baroreceptors
gag reflex
SYMPATHETIC VISCEROSENSORY
visceral pain sensation -
nociceptors
poorly localized
Chain
dorsal root ganglia at T1-L2/L3 spinal cord levels - within the spinal
cord
ventral postero-lateral nucleus of the thalamus (VPL) - reticular
formation
diverse areas of the cerebral cortex, hypothalamus, and intralaminar
nuclei of the thalamus
PARASYMPATHETIC VISCEROSENSORY
Carries
Arterial oxygen tension (PaO2) - arterial pH - chemoreceptors - carotid
bodies
Blood pressure - baroreceptors carotid sinus
Visceral pressure and movement sensation rapidly adapting mechanoreceptors
Visceral stretch sensation slowly adapting mechanoreceptors
Osmolarity osmoreceptors
Temperature internal thermal receptors
Chain
solitary
nucleus, dorsal horn of the spinal cord, or gray matter of the S2 to S4
spinal cord
dorsal
motor
nucleus of the vagus nerve (DMN) - rostral ventrolateral medulla
(RVLM) - anterolateral system (ALS) the spinoreticular tract -
preganglionic parasympathetic motor neuron of a pelvic splanchnic nerve
preganglionic
parasympathetic motor neuron of CN X - intermediolateral cell column
VISCERAL
MOTOR
STRUCTURE
NEUROTRANSMITTER
ACTIVATION OF THE VISCERAL MOTOR
EFFERENT
PATHWAYS
Synapses
between neurons are made in the autonomic ganglia
Parasympathetic
ganglia
Sympathetic ganglia
Preganglionic
neurons
sympathetic
nervous system thoracolumbar
parasympathetic
nervous system craniosacral
Postganglionic
neurons
Adrenal medulla
chromaffin
cells
epinephrine Pheochromocytoma
NEUROTRANSMISSON
Preganglionic
transmitters
Postganglionic
transmitters
Parasympathetic
Sympathetic
Postganglionic
synapses
EFFECTOR ORGANS
SYMPATHETIC
VISCEROMOTOR
mobilize
the body for activity - "fight-or-flight"
paravertebral
ganglia sympathetic chain prevertebral ganglia
Origin of
Preganglionic Neurons
thoracolumbar
lateral
horn - white communicating ramus
head region -
superior cervical ganglion
abdominal
pelvic viscera - splanchnic nerves
poatganglionic
fibers gray rami communicantes
Location of
Autonomic Ganglia
near
the spinal cord
Length of
Preganglionic and Postganglionic Axons
Neurotransmitters
and Types of Receptors
Preganglionic
neurons cholinergic
Postganglionic
neurons
Sympathetic
Adrenergic Varicosities
sympathetic
postganglionic adrenergic nerves
norepinephrine
small densecore vesicles ATP
large
dense core vesicles neuropeptide Y
Adrenal Medulla
chromaffin
cells
epinephrine
norepinephrine phenylethanolamine Nmethyltransferase
pheochromocytoma
norepinephrine
Fight or Flight
Response
PARASYMPATHETIC VISCEROMOTOR
restorative,
to conserve energy -
"rest-and-digest"
Origin of Preganglionic Neurons
cranio sacral
outflow
Location
of Autonomic Ganglia
near,
on, or in the effector organs
Length of
Preganglionic and Postganglionic Axons
Neurotransmitters
and Types of Receptors
preganglionic
neurons are cholinergic
postganglionic neurons cholinergic
Parasympathetic
Cholinergic Varicosities
parasympathetic
postganglionic cholinergic nerves
ACh
small, clear vesicles
large densecore vesicles VIP NO
ENTERIC
myenterlc
plexus (of Auerbach)
submucosal plexus
(of Meissner)
INPUT TO THE
VISCERAL NERVOUS SYSTEM
hypothalamus
paraventrlcular
nucleus - hypothalamospinal & hypothalamomedullary tracts -
perlaqueductal gray (PAG)
hypothalamosplnal
fibers - anterolateral medulla - lateral horn
AUTONOMIC
INNERVATION OF THE ORGAN SYSTEMS
Reciprocal
Functions—Sympathetic and Parasympathetic
reciprocally
or synergistically
SINOATRIAL
NODE
URINARY
BLADDER
micturition
bladder
is filling sympathetic
bladder
is full parasympathetic
PUPIL
size
of the pupil
pupillary
dilator muscle
pupillary constrictor muscle
pupillary
light reflex
accommodation
response
SEVERAL
ORGANS
only
sympathetic innervation
Coordination of Function Within Organs
urinary
bladder
gastrointestinal
tract
Types of Receptors
VISCERAL
REFLEXES
regulatlon
- visceral reflex systems
CONTROL
OF BLOOD PRESSURE
baroreceptors -
nucleus solitarius
"vasodepressor'' -
dorsal motor nucleus of the vagus & nucleus amblguus - vagus nerve -
parasympathetic ganglla In the heart
'vasopressor"
- preganglionic sympathetic neurons - lateral horn -
sympathetic ganglla - postgangllonlc sympathetic fibers
baroreceptor reflex
CONTROL
OF BLADDER FUNCTION
Somatic afferents
viscera! afferents
sympathetic
efferents parasympathetic afferents
somatic motor
efferents
Pain
and temperature
Fullness
of the bladder
Innervation
of the urethral sphincters
internal urethral
sphincter sympathetic visceromotor
external urethral
sphincter deep perineal pouch somatic motor neurons
Onuf nucleus
pudenda! nerve
Innervation
of the detrusor muscle
smooth muscle
parasympathetic visceromotor neurons vesical plexus
Central
control of mlcturltlon
frontal lobe of the
cerebral cortex pons
PAG pontine
micturition center (PMC) pontine storage center (PSC)
Voiding
spinopontospinal
reflex mechanism
Bladder
control after splnal cord Injury
areflexic
automatic micturition detrusor
sphincter dyssynergla
SEXUAL
RESPONSES
neuroendocrlne,
llmblc, autonomic, and somatic
somatic and
visceral afferents and efferents
pudenda! nerve
viscera! nervous system
Engorgement
vaglnal lubrlcatlon
Ejaculation
seminal emission
thoracic sympathetic fibers expulsion of sperm sacral parasympathetic
fibers contraction of the pelvic floor pudenda! nerve
Orgasm
AUTONOMIC
CENTERS
RF
AMYGDALA
BRAINSTEM
Preganglionic
nuclei
Edinger-
Westphal nucleus, superior and inferior salivatory nuclei, the dorsal
motor nucleus of vagus, and the nucleus ambiguus
Nucleus tractus
solitarius
Reticular formation
Control
centers
respiratory
center, cardiovascular control center, and micturition center
Medulla
Vasomotor
center
Respiratory center
Swallowing, coughing, and vomiting centers
Pons
Pneumotaxic
center
Midbrain
Micturition
center
HYPOTHALAMUS
Organization
Neural pathways
Circumventricular organs (CVOs)
Location
Sensory
:
subfornical organ & the organum vasculosum of the lamina
terminalis, both associated with the hypothalamus. The area postrema is
a brainstem CVO
Location
Secretory
: the median eminence (part of the hypothalamus), the
neurohypophysis (posterior pituitary gland), and the pineal gland
Structure
Sensory
functions
Endocrine functions
Clock functions
Temperature
regulation center
Thirst and food intake regulatory centers
LIMBIC SYSTEM
hippocampus,
cingulate cortex, and anterior thalamic nuclei
AUTONOMIC RECEPTORS
β1
receptor in the SA node β1 receptor in ventricular muscle
(agonists)
(antagonists)
G
PROTEINS
G protein–linked
receptors
heterotrimeric
ADRENORECEPTORS
α1
Receptors
excitation (contraction)
Mechanism
of action Gq protein
activation of phospholipase C IP3 Ca2+
α2
Receptors
autoreceptors
heteroreceptors
Mechanism
of action Gi
protein
decrease in cyclic adenosine monophosphate (cAMP)
inhibition
of adenylyl cyclase inhibits adenylyl cyclase
β1
Receptors
heart
excitation
Gs protein increase in cAMP
activation
of adenylyl cyclase cAMP
β2
Receptors
relaxation
Gs protein increase in cAMP
stimulation of
adenylyl cyclase
Responses of Adrenoreceptors to
Norepinephrine and Epinephrine
α1 receptors
β1 receptors
β2 receptors
CHOLINORECEPTORS
Nicotinic
Receptors
autonomic ganglia
(Nn) neuromuscular junction (Nm) adrenal medulla (Nn)
activated
by ACh or nicotine
excitation
ganglionic blockers
(e.g., hexamethonium)
curare
vascular smooth
muscle
male sexual
function
mechanism of action
Muscarinic
Receptors
heart
(M2), smooth muscle (M3), and glands (M3)
inhibitory
in the heart
excitatory in
smooth muscle and glands
activated by ACh
and muscarine
mechanism
of action heart SA node: Gi protein smooth muscle and glands: Gq protein
phospholipase C IP3
direct action of
the G protein SA node
DRUGS
THAT ACT ON THE ANS
TOC
SPINAL
CORD, BRAINSTEM & TRACTS
TOC
SENSORY
& MOTOR
SYNAPTIC
RELAYS
relay nuclei
interneurons &
projection neurons
TOPOGRAPHIC
ORGANIZATION
neural maps
somatotopic map retinotopic tonotopic
DECUSSATIONS
commissures optic
chiasm
TYPES
OF NERVE FIBERS & CONDUCTION VELOCITY
TOC
SENSORY SYSTEM
SENSORY
PATHWAYS FROM THE SENSORY RECEPTOR TO THE CEREBRAL
CORTEX
Sensory
receptors
transduce
electrical energy (receptor potential)
Firstorder
sensory afferent neurons
Secondorder
sensory afferent neurons
relay nuclei
cross at the midline - information originating on one side of the body
ascends to the contralateral thalamus
Thirdorder
sensory afferent neurons
thalamus
Fourthorder
sensory afferent neurons
conscious
perception
NERVE
ENDING = SENSORY
RECEPTORS, EFFECTORS
MUSCLE
SPINDLE = RECEPTOR AND EFFECTOR
EFFECTORS
Terminaison
neurosensorielle, neurosécrétoire, neuromusculaire
SENSORY
RECEPTORS
Sensory
receptors: neurons specialized to detect environmental stimuli and
transmit them through action potentials
Receptive field:
focal area to which the application of an appropriately intense
stimulus will trigger the sensory receptor to initiate an action
potential
EXTERO-CEPTORS
: Skin - Superficie du corps
INTERO-CEPTORS : baro chemo
mechano thermo ENTERO-CE(A)PTORS : Viscera
PROPRIO-CEPTORS : Muscles Tendons Joints -
Posture & Mouvement
TELO oeil oreille olfaction
MECHANO
PHOTO CHEMO NOCI
FREE
NERVE ENDINGS - PAIN & temperature (1)
(Aδ—fast, myelinated fibers) - C—slow, unmyelinated
All tissues - SKIN,
et gaine épithéliale externe de la racine du poil , muscle intestine,
cornea - except cartilage & eye lens
HAIR FOLLICLE
Light
brush - G-hair Aβ D-hair Aδ - RA LT
Skin
movement
- velocity
TERMINAISONS NERVEUSES DES FOLLICULES
PILEUX
(2)
Dans
la gaine conjonctive de certains
poils (génitaux, moustaches, vibrisses...)
ENCAPSULATED
(3)
MEISSNER CORPUSCLE
& MERKEL
DISC -
Mediate
discrimination of FINE spatial differences
MEISSNER =
TACTILE (OVOIDE) -
SMALL (3) - Pressure
(Dynamic)
- Fine / LIGHT TOUCH - Velocity
- Low-frequency vibration - Skin indentation
- twopoint discrimination
Dynamic
deformation - Aβ
Large myelinated fibers - RA LT
Glabrous
skin - palms
& soles
-
Between dermal papillae (surtout
coussinets tactiles)
Skin
motion; detecting slipping objects
MERKEL =
TACTILE EPITHELIAL CELLS
(2) -
PRESSURE (static)
- Location - deep
static touch (eg, shapes, edges)
Large, myelinated fibers
Light touch
Fingertips - superficial skin - hair follicles -
hard palate -
Dermis
Tactile disks associated with peptide-releasing cells
- Transducer is on epithelial cells
Indentation
depth -
Aβ
- SA LT
Fine
tactile discrimination; form & texture perception
PACINIAN
& RUFFINI - Deep
pressure, vibration, stretching of skin
Skin - Dermis -
joint capsules - ligaments- serous membranes - mesenteries
PACINIAN =
LAMELLAR = VATER-PACINI - LARGE
(3) - Mediate
discrimination of COARSE spatial differences -
High-frequency VIBRATION
- Tapping - Pressure
Large myelinated fibers - Onion
-
(surrounding unmyelinated nerve endings)
Deep skin layers - Ligaments - Joints -
Derme, cornée, sous les muqueuses, coeur, pancréas, péritoine, prés gros
vaisseaux
Aβ
- RA
LT
Vibratory cues transmitted by body contact when grasping an object
RUFFINI = BULBOUS
(APLATI) - LARGE (3)
-
STRETCH
- Pressure - joint angle
change
(dermis)
Finger tips plante pieds - Joints capsule
- corps
ciliaire dure mère vaisseaux
Large, myelinated fiber intertwined among collagen fiber bundles Aβ - SA
LT
Skin
strech; direction of object motion,
hand shape & finger postion
(BULBOIDE)
C.
= KRAUSE = GOLGI MAZZONI -
(3)
sous
epiderme, dans conjonctives, épiglotte, cavité orale
(LINGUAL)
C. -
(3)
Dans
muqueuse linguale
Froid
(GENITAL)
C. = DOGIEL -
(3)
semblable bulboide
organes
génitaux externes, papille et aréole du sein
stimulation
tactile (pression légère)
PROPRIO-CEPTORS
JOINT CAPSULE RECEPTORS - Sense
flexion/extension of the joints
GOLGI TENDON ORGAN
- (in series with muscle fibers) - Sense TENSION of tendons
& muscles
MUSCLE SPINDLE
- (in parallel with muscle fibers) - Sense muscle LENGTH - stretch
Intrafusal
muscle fiber, Nuclear chain fiber, Nuclear bag fiber
MECHANO-RECEPTORS - LIGAMENTOUS
MECHANO-RECEPTORS
- OTHERS
Hair cells in auditory & vestibular systems
Baroreceptors in carotid sinus
PHOTO-RECEPTORS
Rods & cones of the retina
CHEMO-RECEPTORS
Olfactory receptors
Taste receptors
Osmoreceptors
Carotid body O2 receptors
NOCI-CEPTORS : Extremes of
temperature & PAIN
Free
nerve endings
Nociceptors
THERMO-RECEPTORS
SOMATO-SENSORY
RECEPTORS
MECHANO-RECEPTORS
THERMO-RECEPTORS
transient receptor
potential (TRP) channels
NOCI-CEPTORS
(skin)
Thermal
or mechanical nociceptors
Polymodal
nociceptors
inflammatory
response
hyperalgesia
C - FIBRE LTM
Touch - C - SA
LT
Pleasant
contact; social interaction
MECHANO-NOCICEPTOR / POLYMODAL NOCICEPTOR
Injurious
forces - C Aδ
- SA HT
Skin
injury; pain
STEPS
IN SENSORY TRANSDUCTION & RECEPTOR POTENTIALS
Sensory
transduction: process in which stimulus is detected, amplified, and
conducted to CNS
Receptor
potential: change in membrane potential in sensory cells caused by
opening of ion channels; typically cells are depolarized
If membrane
potential > threshold potential → action potential (AP) generated
Spatial summation:
“firing” of greater numbers of nerve fibers → ↑ signal intensity
Temporal summation:
↑ frequency of
AP generation → ↑ signal intensity
Stimulus
arrives at the sensory receptor
Ion channels are opened in the sensory receptor
depolarization
photoreceptor
hyperpolarization
receptor
potential or generator potential
graded in size
RECEPTIVE
FIELDS
excitatory
inhibitory lateral inhibition
SENSORY
CODING
modality labeled
lines
location
Threshold
intensity
neural maps
pattern of nerve impulses
duration
ADAPTATION
OF SENSORY RECEPTORS
Adaptation :
sensory receptors adapt (change frequency of AP generation) to varying
extents in the presence of a constant
stimulus
Tonic
receptors: continue to generate APs as
long as stimulus is present
Examples of tonic
receptors: muscle spindles, pressure receptors, slow pain receptors
Phasic
receptors: rapidly ↓ frequency of AP
generation in response to a constant stimulus
Examples of phasic
receptors: Meissner and pacinian corpuscles
Rapidly
adapting - Phasic and very rapidly
onset
offset
receptors
pacinian corpuscles vibrations
Slowly
adapting - Tonic
steady stimulus
receptors steady pressure stimulus
intensity stimulus duration
SOMATO-SENSORY
SYSTEM & PAIN
TOC
SOMATO-SENSORY PATHWAYS
(Krebs LIR
2017 7 Ascending Sensory Tracts)
V1 PDF
OVERVIEW
spinal ganglia
posterior root
3
+ 1 modalities :
PCMLS mechanical
stimuli
ALS
nociceptive
stimuli
SCT
proprioception
MLF
Eye
movements vestibular
A
thalamic or cortical stroke will result in sensory deficits on the
opposite side of the body
Thalamus: arranged somatotopically;
lesions → contralateral sensory deficits
Pain
receptors: adapt very little or not at all
Fast pain: well
localized, sharp in nature, rapid onset and offset, carried by group III
fibers
Slow pain: poorly
localized
Dermatome:
area of skin innervated by single spinal nerve
SPECIFIC
PATHWAYS OF THE SOMATOSENSORY SYSTEM
DORSAL
(POSTERIOR) COLUMN - MEDIAL LEMNISCUS SYSTEM =
PCMLS
- BODY - pressure, vibration, fine touch, [conscious] proprioception
DORSAL
COLUMN SYSTEM (DCS): MEDIAL LEMNISCAL PATHWAY
Sensory
modalities detected by dorsal columns: fine touch, conscious
proprioception, two-point discrimination, vibration
Second-order
neurons decussate in the brainstem (medulla) rather than in the spinal
cord
Dorsal
column lesions → ipsilateral sensory deficits below level of the lesion
general somatic
afferent
Discriminative (fine) touch,
pressure, Vibration, (twopoint
discrimination), Conscious
Proprioception
group II fibers
Fasciculus
graciLis (Lower body, legs)
Fasciculus
cUneatus (Upper body, arms)
GENERAL
ANATOMY
spinal reflex arcs
- posterior columns - fasciculus gracilis - fasciculus cuneatus
somatotopic
organization
internal capsule
and corona radiata
Sensory nerve
ending of pseudounipolar neuron in dorsal root ganglion Ž enters spinal
cord Žascends ipsilaterally in dorsal columns -
dendritic axon
Nucleus
gracilis, nucleus cuneatus (ipsilateral medulla)
Decussates
in medulla Ž ascends contralaterally as the medial lemniscus
VPL
(thalamus)
Projects
to 1° somatosensory cortex
TRANSECTION
Above the
decussation - contralateral
spinal cord (below
the decussation) results in ipsilateral
TRIGEMINAL
SYSTEM - HEAD & NECK
LESIONS
ANTERO-LATERAL
SYSTEM
= ALS -
BODY - SPINOTHALAMIC
- Pain
& Temperature
Sensory
modalities detected by spinothalamic system: pain, temperature, crude
touch
Lateral
spinothalamic tract (pain, temperature)
Anterior
spinothalamic tract (crude touch, pressure)
(light)
nondiscrlmlnatlve touch
lightly myelinated
Adelta fibers - unmyelinated C fibers - free nerve endings
- group III and IV fibers
Adelta
MECHANOSENSITIVE RECEPTORS & FIBERS
Pain &
temperature - Adelta mechanosensitive receptors - Adelta fibers
Adelta
thermoreceptors
: heat activated cold activated
nondiscrlmlnatlve
touch - Adelta
mechanosensitive
fibers
C
FIBERS
polymodal -
chemonociceptors - Itch - thermal and mechanlcal stimulation -
secondary pain
GENERAL
ANATOMY
Lissauer
tract - somatotopically - internal capsule and corona
radlata
1ON Sensory nerve
ending (Aδ and C fibers) of pseudounipolar neuron in dorsal root
ganglion Ž enters spinal cord
1S Posterior horn
(spinal cord)
2ON Decussates in
spinal cord as the anterior white commissure Ž ascends contralaterally
2S VPL (thalamus)
3ON Projects to 1°
somatosensory cortex
TRANSECTION
contralateral
- below
BROWN-SÉQUARD SYNDROME
TRIGEMINAL
SYSTEM - HEAD & NECK
LESIONS
contralateral
THALAMUS
SOMATOSENSORY
CORTEX—THE SENSORY HOMUNCULUS
face, hands, and
fingers
PAIN
nociception free
nerve endings
substance P
opioids
Fibers
for fast pain and slow pain
Fast pain III
Slow pain C
Referred
pain
dermatomal
rule
SPINOCEREBELLAR TRACTS
= SCT
proprioceptive
exteroceptive
POSTERIOR
SPINOCEREBELLAR TRACT
Clarke nucleus
Lower limb position & movement
CUNEOCEREBELLAR
TRACT
upper limb -
Proprioceptive & exteroceptive
fasciculus cuneatus
- accessory cuneate nucleus - ipsilateral cuneocerebellar tract
ANTERIOR
SPINOCEREBELLAR TRACT
anterior horn, -
spinal border cells - lumbar segments - anterior and posterior lobes
modulating
descending tracts - flexor reflex arcs - postural stability
ROSTRAL
SPINOCEREBELLAR TRACT
uncrossed
LESIONS
OF THE SPINOCEREBELLAR TRACTS
ataxias
MEDIAL LONGITUDINAL FASCICULUS = MLF
SPINAL TRACT
ANATOMY & FUNCTIONS
Spinothalamic tract
& dorsal column (ascending tracts) synapse and then cross
Corticospinal
tract (descending tract) crosses and then synapses
TOC
MOTOR SYSTEM
OVERVIEW
Control
of
movement: involves motor cortex, basal ganglia, motor thalamus,
cerebellum, upper & lower motor neurons, and sensory system
MOTOR
NEURONS
Alpha motor neuron: supply extrafusal
muscle fibers → movement
Gamma
motor neurons: supply intrafusal
muscle fibers →
joint proprioception
CONTROL
OF VOLUNTARY MOVEMENT
Voluntary
movements: requires “permission” from basal ganglia & motor thalamus
ORGANIZATION
OF MOTOR FUNCTION BY THE SPINAL CORD - ROLE OF SPINAL CORD TRACTS IN
MOVEMENT
MOTOR
UNITS
Small
motoneurons
Large
motoneurons
MUSCLE
SPINDLES - SENSOR
Types
of muscle sensors
Muscle spindles
Golgi tendon organs
Pacinian corpuscles
Free nerve endings
Types
of muscle fibers
Extrafusal
fibers
Intrafusal
fibers
Muscle spindles
SPINAL
CORD REFLEXES
- MUSCLE
Stretch
(myotatic) reflex—knee jerk
Golgi
tendon reflex (inverse myotatic)
Flexor
withdrawal reflex
SPINAL
ORGANIZATION OF MOTOR SYSTEMS
Convergence
Divergence
Recurrent
inhibition (Renshaw cells)
Role of spinal cord in movement: important in rhythmic and reflexive
movements
Spinal cord tracts
controlling movement: pyramidal and extrapyramidal
Lesions → paraplegia, quadriplegia, spinal or neurogenic shock, upper
motor neuron (UMN) signs, lower motor neuron (LMN) signs
Pyramidal tracts: decussate in the caudal medulla
Pyramidal tracts: corticobulbar, lateral corticospinal, and ventral
corticospinal
Pyramidal tracts: originate primarily from motor cortex and terminate
directly on motor neurons in the brainstem and spinal cord
Lesions → UMN signs
Extrapyramidal tracts: originate in brainstem; do not directly innervate
lower motor neurons
Role of extrapyramidal tracts: reflexes, postural control, control of
movement
Lesions →
inability to initiate movement (akinesia), inability to remain still
(akathisia); extrapyramidal symptoms: tardive dyskinesia, muscle spasms
(dystonia) of neck (torticollis)
Role of medial
descending system: control of posture
Role of lateral
vestibulospinal tracts: stabilizes posture through stimulation of
extensor (antigravity) muscles; promotes equilibrium
Role of medial
vestibulospinal tracts: eye movements, gaze control, head and neck
positioning
Role of pontine
reticulospinal tracts: stimulates extensor antigravity muscles
Role of
medullaryreticulospinal tracts: to inhibit extensor antigravity muscles
Lesion at level of
superior colliculus →
decerebrate posturing or rigidity, also referred to as extensor posturing
Role of tectospinal tracts: reflexive movements of head and neck in
response to visual stimuli
Ventral corticospinal tract: descends in anterior funiculus of spinal
cord; controls axial and proximal muscles
Lateral corticospinal tract: synapses on alpha lower motor neurons;
controls distal limb muscles
Lesions → UMN signs:
hyperreflexia, spasticity, clonus, Babinski sign
Upper motor neurons: tonically inhibitory to lower motor neurons
UMN lesion →
disinhibition of LMN activity →
UMN lesion signs
CONTROL
OF POSTURE (& MOVEMENT) BY THE BRAIN STEM
Motor
centers and pathways
Rubrospinal tract
Pontine
reticulospinal tract
Medullary
reticulospinal tract
Lateral
vestibulospinal tract
Tectospinal tract
Effects
of transections of the spinal cord
Effects
of transections above the spinal cord
CEREBELLUM
- CENTRAL CONTROL OF MOVEMENT
Cerebellum:
coordinates speed, trajectory, and force of movements as they occur;
important in posture and equilibrium
Cerebellar
divisions: pontocerebellum, spinocerebellum, vestibulocerebellum
Role of
neocerebellum: planning and timing of sequential motor movements
Neocerebellar
lesions →
incoordination
of limbs
Role of spinocerebellum: control of precise and purposeful movements
Spinocerebellar lesions →
ataxia, tremor, pendular reflexes
Role of vestibulocerebellum: posture, equilibrium, eye movements
Vestibulospinal lesions →
pendular nystagmus, ataxia
Functions
of the cerebellum
Layers
of the cerebellar cortex
Connections
in the cerebellar cortex
BASAL
GANGLIA - CONTROL OF MOVEMENT
Basal
ganglia: important in initiation of voluntary movements
Basal
ganglia output: always inhibitory in nature
Direct
pathway: disinhibition of motor thalamus →
promotes movement
Lesions
→ difficulty
initiating movements (e.g., Parkinson disease)
Indirect
pathway: inhibition of motor thalamus →
inhibits movement
Lesions → unintentional or
spontaneous movements (e.g., Huntington disease)
MOTOR
CORTEX
- ROLE OF THE CEREBRAL CORTEX IN MOVEMENT
Motor
cortex: comprises premotor, supplementary, and primary motor cortices
Stimulation of primary motor cortex → discrete movement
Stimulation of association motor cortices → complex, patterned
movement
Premotor
cortex and supplementary motor cortex (area 6)
Primary motor
cortex (area 4)
TOC
MOTOR PATHWAYS - UMNs
(Krebs LIR
2017)
V1 PDF
Lower
Motor Neurons : Spinal
cord anterior horn
- Cranial
motor nuclei
- Neuromuscular
junction
Upper
Motor Neurons : Corticospinal
and corticobulbar pathways
- "Extrapyramidal"
pathways
OVERVIEW
voluntary
& Involuntary
Voluntary movement - lateral
corticospinal tract
Involuntary
movement
- Postural adjustments - anterior
corticospinal tract
Postural stability - phylogenetically older pathways - vestibulospinal,
reticulospinal, rubrospinal, and tectospinal
Truncal
stability -
bilateral
FROM
THE CORTEX
crossed - limbs
bilateral - trunk
spinal
reflexes - Influences on afferent (ascending, sensory) systems -
trophic
LATERAL
CORTICO-SPINAL TRACT -
(voluntary
motor)
Origin
giant cells of Betz
Course
corona radiata -
posterior limb ot the internal capsule - cerebral peduncles - basal
pons - pyramids - anterior - medulla - pyramidal decussation
Termination
Function
target
neurons lateral corticospinal tract anterior horn - distal muscle
groups
entire limb -
central pattern generators
Somatotopic
arrangement
motor homunculus
Transection
contralateral
spastic hemiparesis and Babinski sign
ipsilateral spastic
hemiparesis and Babinski sign
ANTERIOR
(VENTRAL) CORTICO-SPINAL TRACT -
(voluntary
motor)
ipsilateral
bilateral
ipsilateral
postural adjustments
Origin
Course
until the
decussation of the pyramids in the medulla
Termination
bilaterally
- ventral white commissure
Transection
CORTICO-SPINAL
TRACT -
Voluntary movement
UMN: 1° motor cortex - descends ipsilaterally (through posterior limb of
internal capsule and cerebral peduncle), decussates at caudal medulla
(pyramidal decussation) Ž descends contralaterally
Anterior horn (spinal cord)
LMN: leaves spinal cord
NMJ (skeletal muscle)
CORTICO-BULBAR
TRACT
corona radiata genu
internal capsule
motor nuclei of the
brainstem bilateral
descending cortical
fibers reticular formation red nucleus
HYPOTHALAMOSPINAL
TRACT
Origin
Course
Termination
Transection
Horner
syndrome
FROM
THE BRAINSTEM
- "EXTRAPYRAMIDAL"
phylogenetically -
proximal truncal musculature - body movement assure postural
stablllty
VESTIBULO-SPINAL
TRACTS
vestibulospinal
system - vestibular nuclei
medial = descendlng medial longitudinal fasciculus - medial vestibular nucleus
- bilaterally
lateral - lateral
vestibular
nucleus = Deiters
- ipsilaterally in the
anteromedial - stimulation of
extensors & inhibition of flexors
Inner
ear - postural adjustments
RETICULO-SPINAL
TRACT
pontine &
rostral medullary reticular formation - ipsilaterally -
anteromedial area of the brainstem
orientation of the
body - muscle tone
Control
of breathing
Emotional
motor system
monoaminergic
neurotransmitters - limbic system
excitability of
spinal motor neurons
Pontine
: stimulatory effect on both extensors & flexors
Medullary
: inhibitory effect on both extensors & flexors
RUBRO-SPINAL
TRACT
red nucleus -
contralateral side - flexors of the upper limb
stimulation
of flexors & inhibition of extensors
TECTO-SPINAL
TRACT
superior
colliculus - cervical spinal cord
control
of neck muscles
TOC
SPINAL
CORD
(Krebs
LIR
2017 5 Spinal Cord)
V1 PDF
(Baillet 49 Metamere
médullaire : système réflexe et programmation du mouvement ) V1 JPG
OVERVIEW
Upper
motor neurons (UMNs)
Lower motor neurons (LMNs)
anterior (ventral) hom posterior (dorsal) horn lateral
horn
31
segments
posterior roots.
anterior roots
dermatome myotorne
FUNCTION
The
spinal cord carries information from the brain and brain stem to
different parts of the body
conduit
function - intrinsic functions
LEVELS OF THE SPINAL CORD
UNIQUE STRUCTURES
Conus
medullaris
Cauda equina
SURFACE ANATOMY OF THE SPINAL CORD
cauda
equlna
enlargements
carvlcal lumbar
conus medullarls
fllum ternlnale
fissures sulci anterior median fissure anterior white commlsaure anterolateral sulcus
posterior median sulcus posterolateral sulcus
funiculi
columns
posterior
column Fasclculus gracilis Fasciculus cuneatus
lateral
column lateral cortlcosplnal tract anterolateral tract
anterior column anterior corticospinal tract
SPINAL MENINGES
dura
mater
lumbar cistern true epldural space
arachnoid mater
subarachnold space
pia mater
denticulate
ligaments filum termlnale
SPINAL NERVES
posterior
roots anterior roots
intervertebral foramen spinal
ganglion anterior posterior rami
Dermatomes
Myotomes
INTERNAL STRUCTURE OF THE SPINAL CORD
anterior,
lateral, and posterior columns
GRAY MATTER
anterior
horn LMNs Renshaw cells
posterior hom sensory Information pain temperature
lateral horn preganglionlc visceral motor cell bodies
Subdivisions of the gray matter
Rexed lamlnae
Anterior horn
motor neurons Renshaw cells
somatotopic distribution
Lateral horn
visceral motor system
Posterior horn
sensory Information discriminative touch and proprioception
pain and temperature
Clarke
nucleus
proprioception
spinocerabellar tract
WHITE MATTER
fasclculi
Anterior column
Anterior cortlcosplnal tract
Other tracts
Lateral column
Lateral cortlcosplnal tract
Spinocerabellar tracts
Spinothalamlc tracts
Other tracts
Posterior column
discriminative touch proprioception
fasciculus gracilis fasclculus cuneatus
BLOOD SUPPLY TO THE SPINAL CORD
Anterior (ASA) and posterior spinal arteries (PSAs)
vertebral-basilar
system the segmental arteries
Great radlcular artery
Anterior spinal artery
Posterior spinal arteries
SPINAL CORD SYSTEMS
central
pattern generators (CPGs)
SPINAL
REFLEXES
Stretch
(myotatic) reflex
la
fibers muscle spindles alpha motor neurons
Inhibitory
lnterneurons
motor neurons
Withdrawal
reflex
flexor
reflex Adelta and C fibers
Reflexes
and Corresponding Levels
CROSS-SECTION
OF THE SPINAL CORD
SPINAL
CORD—LOWER EXTENT
SPINAL
CORD & ASSOCIATED TRACTS
Legs
(Lumbosacral) are Lateral in Lateral corticospinal, spinothalamic
tracts.
Dorsal columns are
organized as you are, with hands at sides. “Arms outside, legs inside.”
Motor
pathways travel away from the brain
Sensory pathways
travel toward the brain
CLINICAL
REFLEXES
PRIMITIVE REFLEXES
LANDMARK
DERMATOMES
LESIONS
OF THE SPINAL CORD
TOC
BRAINSTEM SYSTEMS &
CRANIAL NERVES
TOC
BRAINSTEM
& INTRO CRANIAL
NERVES
(Krebs
LIR 2017 6 BS &
Cranial Nerves)
V1 PDF
(Baillet 51 Système
axial)
V1 JPG
OVERVIEW
posterior cranlal fossa medulla oblongata (or medulla) pons
midbrain peduncles
ascending and descending pathways relay nuclei
It
develops from the mesencephalon (midbrain), the metencephalon (pons),
and the myelencephalon (medulla)
(SURFACE) ANATOMY & (RELATIONSHIP TO) INTERNAL STRUCTURES
tectum
ventrlcular system tegmentum basal portion
reticular
formation
MEDULLA (OBLONGATA)
Blood supply: Vertebral artery (VA), anterior spinal artery
(ASA), PICA
Contents
Lesions Wallenberg syndrome
Other functions
Vomiting center (chemoreceptor trigger zone) (area postrema)
Respiratory regulation reticular formation
Consciousness
Blood pressure (BP) regulation
Anterior surface-motor information
pyramids corticospinal corticobulbar tracts decussation of the pyramids
Inferior ollvary nuclear complex hypoglossal nerve (CN XII)
glossopharyngeal (CN IX) vagus (CN X) accessory (CN XI) nerves
Posterior surface-sensory information
closed, or caudal, medulla central canal
posterior columns fasciculus gracilis fasciculus cuneatus
open, or rostral, medulla fourth ventricle obex
inferior medullary velum nucleus gracllls nucleus cuneatus
gracile tubercle cuneate tubercle
(tuberculum clnereum) spinal trlgamlnal nucleus and tract
PONS
Blood supply: Paramedian branches of the basilar artery and
AICA.
Contents and lesions
medial longitudinal fasciculus (MLF)
MLF syndrome (internuclear ophthalmoplegia) multiple sclerosis
Caloric nystagmus
Other important clinical correlations
Vestibular schwannoma (acoustic neuroma) neurofibromatosis type 2
“Locked-in” syndrome
Osmotic demyelination syndrome (ODS)
Anterior surface (basal pons)
trlgemlnal nerve (CN V) CN VI (abducens) CNs VII VIII (pontomadullary junction)
Posterior sur1ace (roof)
fourth ventricle superior medullary velum superior cerebellar
peduncles
MIDBRAIN
Strokes or lesions in the midbrain give rise to several well-known
syndromes
Blood supply: PCA, SCA, branches of the basilar artery (BA)
Consists of a dorsal tectum (roof), an intermediate tegmentum
(floor), and a base
Anterior surface
cerebral peduncles basis pedunculi (crus cerebrl) CN Ill
(oculomotor) lnterpeduncular fossa
Posterior surface
Inferior and superior colliculli tectum CN IV (trochlear)
BRAINSTEM—VENTRAL VIEW
4 CN
are above pons (I, II, III, IV).
4 CN exit the
pons (V, VI, VII, VIII).
4 CN are in
medulla (IX, X, XI, XII).
4 CN nuclei are
medial (III, IV, VI, XII).
“Factors of 12,
except 1 and 2.”
BRAINSTEM—DORSAL VIEW (CEREBELLUM REMOVED)
Pineal gland—melatonin secretion, circadian rhythms.
Superior colliculi—direct eye movements to stimuli (noise/movements) or
objects of interest
Inferior colliculi—auditory
Your eyes are above your ears, and the superior colliculus (visual) is
above the inferior colliculus (auditory)
INTRODUCTION TO THE CRANIAL NERVES
12 pairs somatic motor and sensory visceral motor and sensory
speclal senses
DEVELOPMENT OF THE CRANIAL NERVE NUCLEI
neural tube alar plate basal plate sulcus limitans
FUNCTIONAL COMPONENTS
COLUMNAR ORGANIZATION
OVERVIEW OF THE CRANIAL NERVES
CN I - OLFACTORY
CN II - OPTIC
CN Ill - OCULOMOTOR
CN IV - TROCHLEAR
CN V - TRIGEMINAL
CN VI - ABDUCENS
CN VII - FACIAL
CN VIII - VESTIBULO-COCHLEAR
CN IX - GLOSSO-PHARYNGEAL
CN X - VAGUS
CN XI - ACCESSORY
CN XII - HYPOGLOSSUS
OVERVIEW OF BLOOD SUPPLY TO THE BRAINSTEM
ARTERIAL SYSTEMS OF THE CNS
THE VERTEBRAL-BASILAR SYSTEM
The vertebral arteries
The posterior spinal arteries
The anterior spinal artery
The posterior inferior cerebellar arteries
The basilar artery
The anterior inferior cerebellar arteries
The superior cerebellar arteries
The posterior cerebral arteries
CRANIAL NERVE SCREENING EXAM
TOC
CONTROL
OF EYE MOVEMENTS CN III IV VI
(Krebs
LIR 2017
9 Control
of Eye Movements)
V1 PDF
OVERVIEW
STRUCTURES
INVOLVED IN EYE MOVEMENTS
EXTRAOCULAR MUSCLES
horizontal
axis
: adduction abduction
vertical axis : elevation depression
intorsion extorsion
Rectus
muscles
tendinous
ring medial
rectus lateral rectus
Oblique muscles
Inferior
oblique muscle elevation and extorsion
superior
oblique muscle
(trochlea) adducted depression abducted intorsion
CRANIAL NERVES THAT
CONTROL EYE MOVEMENTS
Three
pairs of cranial nerves
oculomotor nerve abducens nerve trochlear nerve
(LR6
SO4)3
Oculomotor nerve
3
general
somatic efferent (GSE)
- superior, medial, inferior rectus muscles & the inferior
oblique - levator
palpebrae superioris
general
visceral efferent, or parasympathetic - constrictor pupillae
and ciliary muscles
oculomotor
nuclear complex - midline - rostral midbrain
vlsceral
motor (parasympathetic) - periaqueductal gray (PAG) - ciliary ganglion
Trochlear nerve
4
SO
GSE -
superior oblique
tegmentum of the
mid brain - axons course posteriorly - posterior surface
Abducens nerve 6
LR
GSE
to the lateral rectus muscle
relay
center for the coordination of horizontal eye movements
pons
MEDIAL LONGITUDINAL
FASCICULUS
vestibular
nuclei - descending and ascending
ascending -
vestibular nuclei - eye movements - vestibuloocular reflex - conjugate
gaze - heavily myelinated
GAZE
synergistic
movement of both eyes - fovea
horizontal - vertlcal plane - rotate
horlzontal gaze - parameclian pontine reticular formation (PPRF)
vertlcal gaze - (rMRF)
HORIZONTAL
GAZE
WIRING OF
HORIZONTAL GAZE
lateral
rectus (CN VI, abducens) - medial rectus (CN Ill, oculomotor) - abducens
nucleus
SACCADES
rapid
eye movements - orient our gaze
PPRF
- frontal eye fields (FEFs)
superior
colliculus - PPRF
Reflexive
saccades = prosaccades
superior
colliculus - superficial
layer - lateral geniculate nucleus
deeper layers -
motor neurons - PPRF
right
lateral geniculate nucleus
Volitional
saccades
Antisaccade
Memory saccades
Predictive saccade
SMOOTH
PURSUIT
tracking
a slowly moving object - cortical information - cerebellar information - vestibular information
both sides of the
cortex - keep
Ipsilateral
pontine nuclei - contralateral cerebellum - vestibular nuclei - abducens
nucleus
VESTIBULOOCULAR
REFLEX (VOR)
keep
an image stable on the retina
vestibular organ
horizontal
canal - vestibular nucleli - contralateral
-
abducens -
contralateral
- oculomotor
NYSTAGMUS
horizontal
nystagmus
vestibular
optokinetlc
left-beating
nystagmus
visual
stimuli
Cold water caloric
testing : Vestibular nystagmus
endolymph
- COWS (cold, opposite; warm, same) - temperature gradient
Warm water caloric
testing
VERTICAL GAZE
pretectal
area - FEFs - superior colliculus
oblique eye
movements
DISCONJUGATE GAZE
adduct
- convergence - accommodation
abduct - divergence
both
occipital lobes - lateral geniculate nuclei in the thalamus -
vergence centers
Accommodation -
focus on a near object - fovea
converge
- (adduct)
refractive power
-increasing the curvature
puplis must
constrict - depth of field
=
near triad
parasympathetic
Edinger-Westphal - constrictor pupillae muscles - cillary muscles
TOC
SENSORY
& MOTOR INNERVATION OF THE HEAD & NECK : CRANIAL NERVES V VII IX
X XI XII
(Krebs
LIR
2017 10)
V1 PDF
OVERVIEW
SENSORY
GSA - General
SOMATIC Afferent
Discriminative touch, pain, temperature, pressure, proprioception,
vibration
Receptors skin, muscles, joints - meninges & mucosa
Head
neck
V VII
IX X
GVA - General
VISCERAL Afferent
Head
neck thorax abdomen
IX X
SVA - Special
Visceral Afferent
Taste
VII IX X
SSA - Speclal
Somatic Afferent
Hearing
& Balance
VIII
MOTOR
GSE - General
Somatic Efferent
SKELETAL muscles derived from SOMITES
III
IV VI extraocular
muscles
XII tongue
GVE -
General
VISCERAL Efferent
PREganglionic PARAsympathetic
- cranial, thoracic, & abdominal
glands in the head & neck
VII IX X
Ill eye
SVE - Speclal
VISCERAL efferent
=
BRANCHIAL efferent BE
SKELETAL muscles derived from pharyngeal
arches = jaw, face, larynx, & pharynx
V Mastication
VII Facial expression
IX X pharynx and larynx
XI some muscles in the back & neck
CRANIAL NERVE NUCLEI
Located in tegmentum portion of brainstem (between dorsal and
ventral portions):
Midbrain—nuclei of CN III, IV
Pons—nuclei of CN V, VI, VII, VIII
Medulla—nuclei of CN IX, X, XII
Spinal cord—nucleus of CN XI
Lateral nuclei = sensory (aLar plate).— Sulcus limitans—
Medial nuclei = Motor (basal plate)
OLFACTORY I
Smell (only CN without thalamic relay to cortex)
OPTIC II
Sight
OCULOMOTOR III
Eye
movement (SR, IR, MR, IO), pupillary constriction (sphincter pupillae),
accommodation (ciliary muscle), eyelid opening (levator palpebrae)
TROCHLEAR IV
Eye movement (SO)
ABDUCENS VI
Eye movement (LR)
VESTIBULOCOCHLEAR VIII
Hearing, balance
TRI-GEMINAL
V
midpons - sensory ganglion
facial sensation - three major
divisions -
ophthalmlc (V1) - maxillary (V2) - mandlbular (V3) - trlgemlnal gangllon
somatosensation
from anterior 2/3 of tongue
SENSORY
COMPONENT
3 :
discriminative touch, vibration, conscious proprioception - pain and
temperature - nonconscious proprioception
GSA
CHIEF SENSORY NUCLEUS
midpons - trigemlnal ganglion
third-order neurons
Trigemlnal lemnlscus
second-order postsynaptlc fibers - medial lemniscus - ventral
posteromedlal nucleus (VPM) of the thalamus
Posterior
trigeminothalamlc tract
Somatotoplc
arrangement
SPINAL
TRACT & NUCLEUS
substantla gelatlnosa - tract of Lissauer
Pain & temperature fibers
Anterior trigeminothalamlc tract
splnothalamlc tract
Somatotopic
arrangement
MESENCEPHALLC
NUCLEUS
nonconsclous proprioception - pseudounipolar cells
reticular formation and the cerebellum - motor reflex - jaw-Jerk
reflex
MOTOR
COMPONENT OF CN V - SVE -
NUCLEUS
muscles
of Mastication
Dampening of loud noises (tensor
tympani muscle)
midpons - motor root - mandibular division (V3)
JAW-JERK
REFLEX
MASTICATION MUSCLES
3 muscles close jaw: masseter, temporalis, medial pterygoid (M’s munch).
Lateral pterygoid protrudes jaw.
All are innervated by mandibular branch of trigeminal nerve (CN V3).
FACIAL
VII
pontocerebellar
angle
Eye
closing (orbicularis oculi)
Auditory volume
modulation (Stapedius)
Lacrimation
MOTOR
COMPONENT
SVE - FACIAL NERVE
PROPER
muscles
of Facial expression movement
- facial nucleus
Somatotopic
arrangement
upper
face cingulate gyrus
Lesions
GVE
parasympathetic
- NERVUS INTERMEDIUS
pontine
tegmentum -
superior salivatory nucleus - pterygopalatine - submandibular ganglia
secretomotor - Salivation
(Submandibular
& Sublingual
glands
are innervated by CN Seven)
SENSORY COMPONENT
GSA
geniculate ganglion - trigeminal nuclear
complex
SVA
taste
from anterior 2/3 of tongue (chorda tympani)
solitary tract - nucleus
solitarius
GLOSSOPHARYNGEAL
IX
Taste & sensation from posterior 1/3 of tongue
Swallowing
Salivation (parotid gland)
Monitoring carotid body and sinus chemo- and baroreceptors
Elevation of pharynx/larynx (stylopharyngeus)
superior & inferior glossopharyngeal ganglia
SENSORY
COMPONENT
GSA spinal trigeminal nucleus
superior
glossopharyngeal ganglion
spinal
tract of V - spinal nucleus of V - VPM of the thalamus
chief
sensory nucleus
GVA inferior sallvatory nucleus
carotid
body - gag reflex - inferior glossopharyngeal ganglion
chemoreceptors
- baroreceptor - visceral
sensations
-
inferior
glossopharyngeal ganglion
- the solltary tract - nucleus solitarius
solltary
tract - nucleus
ambiguus - gag reflex
SVA nucleus solitarius
taste - inferior
glossopharyngeal ganglion
nucleus
solitarius - ipsilateral
VPM
MOTOR
COMPONENT
SVE = BE nucleus amblguus
nucleus
ambiguus - third
branchial arch - bilateral - corticobulbar tract
GVE
nucleus
ambiguus
- inferior salivatory nucleus - hypothalamus and reticular formation
nucleus
ambiguus
- carotid
body and sinus - vasodilation
inferior
salivatory nucleus - secretomotor
input - parotld gland
THE
GAG REFLEX
nucleus
solitarius - nucleus ambiguus
VAGUS X
Taste from supraglottic region
swallowing
soft palate elevation
midline uvula
talking
cough reflex
parasympathetics to thoracoabdominal
viscera
monitoring aortic arch chemo- and
baroreceptors
medulla - posterior to the olive
- anterior
to the inferior cerebellar peduncle - Jugular foramen - superior vagal (jugular) ganglion - inferior vagal (nodose) ganglion
dorsal motor nucleus of the vagus (GVE) parasympathetic motor
SVA-taste
SENSORY
COMPONENT
GSA spinal nucleus of V
general
sensation - inferior vagal ganglion - superior vagal ganglion -
spinal tract of V - spinal nucleus of V - anterior trigeminothalamic -
VPM of the thalamus
GVA
nucleus solitarius
inferior
vagal ganglion - solitary
tract - nucleus solitarius - reticular formation -
hypothalamus
MOTOR
COMPONENT
SVE nucleus ambiguus
nucleus
ambiguus - dorsal motor nucleus of the vagus
heart - nucleus ambiguus
GVE nucleus ambiguus
VAGAL
NUCLEI
Nucleus
tractus Solitarius - VII, IX, X
Visceral
Sensory information (eg, taste, baroreceptors, gut distention) - May
play a role in vomiting
Nucleus aMbiguus -
IX, X
Motor
innervation of pharynx, larynx, upper esophagus (eg, swallowing, palate
elevation)
Dorsal motor
nucleus
- X
Sends
autonomic (parasympathetic) fibers to heart, lungs, upper GI
ACCESSORY
XI
Head
turning, shoulder shrugging (SCM, trapezius)
(SVE)
splnal accessory nucleus - Jugular foramen
cortlcobulbar - sternocleidomastold muscle descends
ipsilaterally - Trapezius muscle cross the midline - eye-hand
coordination
HYPOGLOSSAL
XII
Tongue
movement
GSE
hypoglossal nucleus - medulla - anterolateral sulcus - hypoglossal
foramen
corticobulbar fibers - genioglossus muscle - crossed
CRANIAL NERVE REFLEXES
Accommodation
Corneal
Cough
Gag
Jaw jerk
Lacrimation
Pupillary
CRANIAL NERVE LESIONS
TOC
HEARING
& BALANCE CN VIII
(Krebs LIR 2017 11 &
Costanzo
BRS 2018)
V1 PDF
SSA
auditory canal - Internal auditory meatus - "hair
cells"
TOC
AUDITION - HEARING
Outer ear:
comprises pinna and external auditory canal
Middle ear:
comprises tympanic membrane, malleus, incus, and stapes
Inner ear:
comprises bony labyrinth (semicircular canals, cochlea, vestibule) and
fluid-filled membranous labyrinth
Scala vestibuli and
tympani: contain Na+-rich perilymph
Scala media:
contains K+- rich endolymph
Organ of Corti:
contains inner and outer hair cells needed for audition; these cells
have cilia embedded in tectorial membrane
Pathway of
sound: sound waves directed into external auditory canal → tympanic
membrane vibrates → ossicles vibrate → fluid displaced in inner ear
Basilar
membrane: vibrations force hair cells against tectorial membrane → changes
in K+ conductance →
hyper/depolarization
High-frequency
sounds: stimulate hair cells at base of basilar membrane to vibrate
Low-frequency sounds: stimulate hair cells at apex of basilar membrane
to vibrate
SOUND WAVES
pitch -
Frequency hertz (Hz)
amplltude - loudness - Intensity decibels (dB)
20 - 20,000
Hz
STRUCTURES OF THE EAR - STRUCTURES INVOLVED IN HEARING
OUTER (EXTERNAL) EAR
aurlcle -
external auditory meatus - tympanic membrane
Transfers
sound waves via vibration of tympanic membrane
MIDDLE EAR
Air-filled
space
eustachian
tube
Bones
In the middle ear
auditory
ossicles - tympanic membrane - malleus
incus - stapes
- oval window
ossicles
vibrate - displacing fluid - inner ear
Ossicles
conduct & amplify sound from tympanic membrane to inner ear
Muscles
in the middle ear
tensor
tympani - stapedlus muscle
INNER EAR
Snail-shaped, fluid-filled cochlea
Contains basilar membrane that vibrates 2° to sound waves.
Vibration transduced via specialized hair cells Ž- auditory nerve
signaling -Ž brainstem
bony labyrinth - semicircular canals - vestibule
cochlea
membranous labyrinth
perilymph - endolymph
-
high
potassium (K+)
(Na+)
vestibular
portion
= otolith
organs (utricle and saccule) & three semicircular canals
IMPEDANCE MATCHING
Mechanism
Damping
tensor
tympani - stapedlus muscle
attenuation
reflex
STRUCTURE OF THE COCHLEA = auditory portion :
THREE TUBULAR CANALS
crosssection
of the cochlea
membranous
labyrinth
- organ of Corti
basilar membrane -
organ of Corti
3 CHAMBERS
Scala vestibuli & scala tympani
perilymph
high [Na+]
helicotrema
Scala media
Relssner
(or vestlbular) membrane - basilar
membrane
endolymph
high [K+]
organ
of Corti
(vestlbular duct -
tympanic duct
stria vascularis)
LOCATION & STRUCTURE OF THE ORGAN OF CORTI
receptor
cells - stereoCilia
spiral
ganglion
Hair cell types
Inner
hair cells few in number
Outer
hair cells
greater in
number
Reticular lamina
(rods of Corti)
Tectorial membrane
HAIR
CELL FUNCTION
Hair
cell structure
Stereocilia
(kinocilium)
tip
links - mechanoelectrical transduction (MET)
STEPS
IN - AUDITORY MECHANO-TRANSDUCTION - BY THE ORGAN OF CORTI
-
PHYSIOLOGY OF SOUND PERCEPTION IN THE INNER EAR
Round
window
Endolymph
stria
vascularis
Perilymph
endocochlear
potential
Receptor
currents
Potassium
recycling
amplified
auditory
hair cells
cochlear
microphonic potential
basilar
membrane - tectorial membrane
vibration
bending of cilia K+ conductance - cochlear microphonic
potential
Basilar membrane
point of
maxlmal displacement -
tonotopy
Inner & outer hair cells
depolarlzatlon
- hyperpolarlzatlon
tip links
- mechanotransduction - sensitivity
Frequency selectlvlty
efferents
Otoacoustlc emissions
HOW SOUND IS ENCODED - AUDITORY ENCODING
Each
frequency leads to vibration at specific location on basilar membrane
(tonotopy)
map
Low
frequency heard at apex near
helicotrema (wide and flexible)
High
frequency heard best at base of
cochlea (thin and rigid)
Hearing range
(presbycusis)
Loudness
Hair cell
output
Sensory
nerve output
Frequencies
auditory
place coding
Fine-tuning
cochlear
amplifier
CENTRAL AUDITORY PATHWAYS
frequency
(pitch),amplitude (volume), and location
crossed or
uncrossed
tonotopic
representation
organ of Corti
spiral
ganglion
modiolus
cerebellopontine
angle
trapezoid
body
Superior
olivary nucleus
lateral
lemniscus
Nucleus of
the inferior colliculus
Medial
geniculate nucleus (MGN)
- brachium of inferior
colliculus
- sublenticular part of the internal capsule
Transverse
temporal gyri of Heschl/primary auditory cortex - (Wernicke area)
CENTRAL PATHWAY FOR PITCH & VOLUME
spiral
ganglion
cochlear nuclei - posterior and
anterior nucleus
lateral lemniscus
inferior
colliculus
Medial
geniculate nucleus (MGN)
- brachium of inferior
colliculus
primary
auditory cortex
CENTRAL
PATHWAYS FOR SOUND LOCALIZATION
vertlcal
plane - horizontal plane
Vertical
sound mapping - directly reflection
horizontal
spatial mapping
Time difference detection at low frequencies
medial
superior olivary nucleus (MSO)
- coincidence detectors - temporal summation
Intensity difference detection at high frequencies
cochlear
nuclei - lateral superior olivary nucleus (LSO)
- medlal
nucleus of the trapezoid body
CONVERGENCE OF PATHWAYS
inferior
colliculus
primary
auditory cortex
(Wernicke area)
HEARING DEFECTS
TOC
VESTIBULAR SYSTEM - BALANCE
equilibrium
Role
of vestibular system: posture, balance, control of head and eye
movements
Role of
semicircular canals: detect rotation and angular acceleration
Role of utricle and
saccule: detect linear acceleration
Kinocilium: longest
cilium on each hair cell
Vestibular
transduction: bending of hair cells with movement → generation of an
action potential
Stereocilia bend
toward kinocilium → hair cell depolarized/excited
Stereocilia bend
away from kinocilium → hair cell hyperpolarized/inhibited
Hair cells no
longer stimulated or inhibited once endolymph “catches up” with cupula
Vestibular-ocular
reflexes: stabilize visual images by compensating for head movement
Nystagmus: may
indicate vestibulocerebellar injury
Direction of
nystagmus: defined as direction of the fast phase of eye movement
Vestibular system:
drives slow phase of nystagmus; brainstem: drives fast phase of
nystagmus
The
vestibular system maintains balance and coordinates head and eye
movements
Vertigo results
from disruption of the vestibular system
VESTIBULAR
ORGAN (SYSTEM) = LABYRINTH
three
perpendicular semicircular canals - (anterior, posterior,&
horizontal) - ampulla - vestibular hair cells
otolith
organs - utricle & saccule
K•·rlch
endolymph
receptors
are hair cells
cupula - kinocilium
- stereocilia
(STEPS
IN) VESTIBULAR TRANSDUCTION
PHYSIOLOGY
OF BALANCE
linear acceleratlon
rotatlonal
accelaratlon
SEMICIRCULAR
CANAL FUNCTION =
KINETIC LABYRINTH
- 3 SCC
- ROTATIONAL
ampullary
crest, or crista ampullaris
- cupula
endolymph
angular acceleration & deceleration -
kinocilium
Hair cells -
ampulla - crista
head is rotated
counter clockwise (left)
stereocilia are
bent toward the kinocilium - depolarizes
stereocilia are
bent away from the kinocilium - hyperpolarizes
When the head
suddenly stops moving
OTOLITH
ORGAN FONCTION = STATIC
LABYRINTH
-
utricle saccule
- LINEAR
macula
- otolithic membrane - otoliths
linear
acceleration - gravity
Hair
cells - kinocilium
Mechanotransduction
Hair cell orientation
striola
utricle
saccule
CENTRAL
VESTIBULAR PATHWAYS
Hair
cells of labyrinth structures → vestibular ganglion → vestibular nuclei
in brain stem → cerebellum, MLF, spinal cord, thalamus
vestibular
nuclei
- tegmentum
lateral
veatibular nuclear group & medial vestibular nuclear group
Medial & superior
nuclei
lateral vestibular nucleus
inferior vestibular nucleus
VESTIBULO-OCULAR
REFLEXES
abducens nucleus
nystagmus
direction of the
nystagmus - same direction as the head rotation
postrotatory
nystagmus
opposite direction
of the head rotation
TESTING
VESTIBULO-OCULAR REFLEXES
Bárány
test
caloric test - Warm
water - Cold water
VESTIBULO-CERVICAL
REFLEX
rotatlonal
movements
descending medlal
longltudlnal fasclculus (or medlal vestlbulosplnal tract)
VESTIBULO-SPINAL
REFLEX
descending medial
longitudinal fasciculus (or medial vestibulosplnal tract) & lateral
vestlbulosplnal tract
CORTICAL
PROJECTIONS
primary and
secondary somatosensory areas
TOC
BRAINSTEM
SYSTEMS, RETICULAR FORMATION & REVIEW
(Krebs
LIR 2017
12 BS
systems, Reticular Formation & Breathing Center Review)
V1 PDF
OVERVIEW
consciousness
- (central pattern generators [CPGs])
THE
RETICULAR FORMATION
tegmentum
- intemeurons
lateral
zone
medial zone
neurotransmitter
systems
ascending ratlcular
activating system (ARAS)
LATERAL
ZONE
afferent
- spinoreticular tract
- consciousness
MEDIAL ZONE
efferent
- reticulosplnal tract - muscle tone
NEUROTRANSMITTER
SYSTEMS
aminerglc
systems (DA, NE,
5-HT)
DOPAMINERGIC
SYSTEMS
Reward
meso-cortico-limbic
DA system
drug-seeking
behavior
Emotlonal learning
& memory
DOPAMINERGIC
PATHWAYS
Commonly
altered by drugs (eg, antipsychotics) & movement disorders (eg,
Parkinson disease)
The mesocortical
& mesolimbic pathways are involved in addiction behaviors - Motivation
& reward
Mesocortical
Ventral
tegmental area (VTA)
→
prefrontal cortex
Motivation
& reward
dimin.
activity
→ negative
symptoms
Antipsychotics
have limited effect
Mesolimbic
Ventral
tegmental area →
nucleus
accumbens
Motivation
& reward
augm.
activity
→ positive symptoms
1°
therapeutic target of antipsychotics
Nigrostriatal
Substantia
nigra → dorsal
striatum
Motor
control (pronounce “nigrostrideatal”)
dimin.
activity
→
extrapyramidal
symptoms
Significantly
affected by antipsychotics and in Parkinson disease
Tuberoinfundibular
Hypothalamus
→
pituitary
Regulation of prolactin secretion
dimin.
activity
→
augm. prolactin
Significantly
affected by antipsychotics
NORADRENERGIC
(NOREPINEPHRINE, NE) SYSTEMS
locus
ceruleus [LC]
- tonic - phasic
Wakefulness
catecholamlnes
glucocorticoid hormones
Attention disorders
monoamine
hypothesis
Alzheimer disease
microglia
SEROTONERGIC
SYSTEMS
raphe
nuclei - prefrontal cortex, thalamus, basal ganglia, cranial nerve nuclei
neurotrophic
factor
thermosensitive
Pain
Sudden infant death
syndrome (SIDS)
chemoreceptors
stimulate respiration
OTHER
NEUROTRANSMITTER SYSTEMS
Cholinergic
neurons
Hlstaminerglc
neurons
BREATHING
CENTER
CENTRAL
PATTERN GENERATOR CPG
posterior
respiratory group
anterior
respiratory group
tonaillar
herniation
NONRESPIRATORY
FUNCTIONS OF RESPIRATORY NEURONS
Neuronal
control of emesis
area postrema
Hiccuping
and coughing
CLINICALLY
ORIENTED REVIEW OF THE BRAINSTEM
TOC
HIGHER CORTICAL FUNCTION
LEARNING
& MEMORY
Memory tracts:
facilitated pathways for signal transmission important in formation of
memories
Short-term memories
: last only for seconds or minutes unless converted to long-term
memories
Intermediate
long-term memories : last for days to weeks unless converted to
long-term memories
Long-term memories
: last for years; mechanism involves synaptic structural and chemical
changes
LANGUAGE
Language
comprehension: Wernicke area; lesions cause receptive aphasia
Verbalization of
language: Broca area; lesions cause expressive aphasia
Language center:
present in left hemisphere in most individuals, even if left-handed
Right middle
cerebral artery strokes can present with left-sided weakness and
sensory deficits, dysarthria and dysphagia but not aphasia, and left-
sided neglect
BRAIN
WAVES
Brain waves:
synchronous firing of millions of neurons can be detected on surface of
the head by EEG
Alpha waves: seen
in awake but resting state
Beta waves: seen in
awake but alert state
Theta waves: seen
in healthy children and in adults with brain disorders
Delta waves: seen
in very deep sleep, infants, and patients with severe brain disease
SLEEP
Sleep-wake
cycle: driven by the suprachiasmatic nucleus of hypothalamus
Classification of
sleep: divided into NREM and REM sleep
Most sleep time is
spent in NREM sleep.
Stage 2 NREM: most
of time spent in this phase, characterized by sleep spindles and K
complexes on EEG
NREM sleep:
progress from very light sleep (stage 1) to stage 2, where most time is
spent, to very deep sleep (stages 3 and 4)
TOC
CEREBRAL
CORTEX
(Krebs
LIR
2017 13)
V1 PDF
OVERVIEW
ANATOMY
OF THE CEREBRAL HEMISPHERES
HISTOLOGICAL ORGANIZATION OF THE CORTEX
neocortex
- paleocortex - archicortex
PYRAMIDAL & GRANULAR NEURONS
lntemeurons
- agranular cortex - granular cortex
CYTOARCHITECTURE
SUBCORTICAL FIBER BUNDLES
ASSOCIATION FIBERS
Superior longitudinal fasciculus
arcuate
fasciculus
Inferior fronto-occlpltal fasciculus
uncinate
fasciculus
Cingulum
cingulate
and parahippocampal gyri
limbic
lobe
COMMISSURAL FIBERS
Corpus callosum
splenium
- genu - forceps minor - forceps major
Anterior and posterior commlssures
PROJECTION FIBERS
corona
radiata
internal capsule
Anatomy of the internal capsule
anterior
limb - posterior limb
Fibers of the internal capsule
FRONTAL
Major areas
Prefrontal
cortex, premotor cortex, primary motor cortex, frontal eye fields, Broca
area
Functions
Movement
(primary motor & premotor cortex)
Eye
movements (frontal eye fields)
Social
judgment (prefrontal cortex)
Language
production (Broca area)
Executive
functions
PARIETAL
Major
areas
Primary
sensory cortex
Functions
Sensation
(primary sensory cortex)
Spatial
relationships
-
Gerstmann syndrome
Vision
Attention
-
Contralateral neglect
-
Apraxia - Balint syndrome
OCCIPITAL
Major
areas
Primary
visual cortex, association visual cortex
Functions
Vision
(primary and association visual cortices)
Visual
recognition (association cortices)
TEMPORAL
Major
areas
Primary
auditory cortex, hippocampus, amygdala, Wernicke area
Functions
Hearing
(primary auditory cortex)
Auditory pathway
Memory
(hippocampus)
Emotion -
Klüver-Bucy syndrome
Seizure activity
Language
comprehension (Wernicke area)
FUNCTIONAL
AREAS OF THE CORTEX
primary
cortical areas
association areas
PRIMARY
AREAS & THEIR UNIMODAL ASSOCIATION AREAS
MOTOR - FRONTAL
primary motor area - precentral gyrus - corticospinal and corticobulbar
tracts
somatotopy - motor homunculus
Primary motor area lesion
Supplementary motor complex
premotor & supplementary motor areas
Supplementary
motor complex lesion
apraxia
SENSORY
- PARIETAL
primary somatosensory cortex - postcentral gyrus
posterior column-medlal lemnlscus system - spinothalamlc tract -
trigeminal lemniscus/trigeminothalamic tract
posterior limb of the internal capsule - somatotoplc organization -
sensory homunculus
Cortlcal plasticlty
Lateral inhibition
Primary somatosensory cortex leslon
Somatosensory association area
tactile agnosia - astereognosls
VISUAL
- OCCIPITAL
Primary visual cortex
calcarine sulcus - lateral geniculate nucleus - optic radiations
retinotopic organization
Primary visual cortex lesion
Visual association area
visual agnosla
AUDITORY
- TEMPORAL
primary auditory cortex - superior temporal gyrus - Heschl gyri - medial
geniculate nucleus - tonotoplc arrangement
Primary auditory area lesion
Auditory association area
acoustic verbal agnosia
Wernicke area
OTHER PRIMARY SENSORY AREAS
TASTE
lnsula - lateral sulcus TPF
OLFACTION system
entorhinal cortex - medial Temporal lobe
HETEROMODAL ASSOCIATION AREAS OF THE
CORTEX
FRONTAL
ASSOCIATION AREAS
prefrontal cortex - superior and lateral parts
attention & motor responses to stimuli
Inferior and medlal portions
Size
Function
working memory - morality
Innervation
monoamlnerglc systems - dopamine, noreplnephrlne, and serotonin receptors
Lesions
Phineas Gage
PARIETAL
ASSOCIATION AREAS
posterior parietal cortex
Function
Lesions
dominant hemisphere - contralateral neglect syndrome
TEMPORAL
ASSOCIATION AREAS
fusiform gyrus
agnosla
prosopagnosia
LANGUAGE
Broca & Wernicke
CLASSICAL CONCEPTS OF THE NEUROBIOLOGY OF
LANGUAGE
(prosody) -
arcuate fasciculus
Broca area
Inferior frontal gyrus
Wernicke area
Lesions
aphasia - dysarthrias
Broca aphasia
expressive or productive aphasia
Wernicke aphasia
receptive or sensory aphasia
Conduction aphasia
MODERN CONCEPTS ABOUT THE NEUROBIOLOGY OF
LANGUAGE
(semantic processing)
THE MIRROR NEURON SYSTEM
Function
Motor !earning
Empathy
Clinical significance
SEX DIFFERENCES IN THE CEREBRAL CORTEX
White
matter tracts
Cortex
BLOOD
SUPPLY TO THE CORTEX
TOC
THALAMUS
(Krebs
LIR
2017
14)
V1 PDF
OVERVIEW
ANATOMY
Surrounding
the third ventricle, just above the midbrain
11 nuclei
lnterthalamlc
adhesion
MEDIAL
& LATERAL NUCLEI
internal
medullary lamina
-
ANTerior nucleus
medial
group
- dorsomedial nucleus (DM)
lateral
group
:
Dorsal tier
lateral
dorsal (LD) - lateral posterior
(LP) - PULvinar - LP pulvinar-complex
Ventral tier
ventral
anterior (VA) - ventral lateral
(VL) - ventral posterior (VP)
ventral
poaterolateral (VPL) - ventral
poatero- medial (VPM)
VI intermediate ?
Geniculate
nuclei
lateral
geniculate nucleus (LGN) - the
medial geniculate nucleus (MGN)
INTRALAMINAR NUCLEI
centromedian
(CM) and parafascicular (PF)
SURROUNDING NUCLEI
thalamic
reticular nucleus (TRN)
FUNCTIONS
OF THE THALAMIC NUCLEI
Relay
nuclei (motor, sensory, and limbic) - Association nuclei
- lntralaminar nuclei
- reticular nucleus (TRN)
projection
neurons - lnterneurons
Sensory
relay station
- Major relay for all ascending sensory information except olfaction
Emotion
and memory
Motor
relay station
Lesion
associated with motor and sensory deficits
- thalamic pain syndrome
INPUTS
TO THALAMIC NUCLEI
specific inputs
(drivers) - regulatory inputs (modulators)
FIRING
PATTERNS
Tonic firing -
burst firing
RELAY
NUCLEI
specific (driver)
input - nonspecific (modulator) input
SENSORY
RELAY NUCLEI
Spinothalamic
& dorsal columns/medial lemniscus - Vibration,
Pain, Pressure,
Proprioception (conscious), Light touch, temperature -
VPL - 1°
somatosensory cortex (parietal lobe)
Trigeminal and
gustatory pathway - Face sensation, taste -
VPM - 1° somatosensory
cortex (parietal lobe) - Very Pretty Makeup goes on the Face
Superior
olive & inferior colliculus of tectum - Hearing - MG - 1° auditory cortex
(temporal lobe) - Medial = music (hearing)
CN II,
optic chiasm, optic tract - Vision - LG - 1° visual cortex
(occipital lobe) - Lateral = light (vision)
Modulatory
system
MOTOR
RELAY NUCLEI
Basal ganglia,
cerebellum
- VA VL -
primary Motor (frontal lobe)
& motor associatlon (supplementary motor complex) cortlces - Venus Astronauts Vow to
Love Moving - tonic
inhibition
Cerebellum, globus
pallidus -
VL Relay
motor information - Primary motor cortex and supplementary motor area
Cerebellum,
globus pallidus - VA Relay motor planning
information - Prefrontal cortex
Output
from the basal ganglia
striatum
Output
from the cerebellum
LIMBIC
RELAY NUCLEI
ANT & LD
mammlllary body -
ANT - mammillothalamic tract - cingulate cortex - prefrontal
& parietal cortices
entorhinal
cortex - LD - cingulate, prefrontal, and parietal cortices
DM
cingulate
gyrus - prefrontal and orbitofrontal cortices
ASSOCIATION
NUCLEI
transthalamic -
corticocortical connections - temporal summation
PUL
medial pul - DM
Visual
processing
retina - visual
association cortex - visual salience
visuospatial
working memory
Auditory
processing
auditory
association cortex - superior temporal gyrus
DM
prefrontal cortex
basal ganglia
amygdala
prefrontal cortex
cingulate gyrus and
entorhinal cortex
Executive
control
Olfactory
processing
INTRALAMINAR
NUCLEI
CM/PF
Arousal
function
cholinergic
innervation - dopaminergic input
Goal-oriented
behavior
striatum
facilitating
goal-oriented behavior
THALAMIC
RETICULAR NUCLEUS
TRN
GABAergic
"gatekeeper of the
gatekeeper''
selective attention
CONSCIOUSNESS
BLOOD
SUPPLY
TOC
VISION
- VISUAL SYSTEM - CN II
(Krebs LIR 2017 15 &
Costanzo BRS 2018) V1 PDF
OVERVIEW
visible
light
Pathway
of light → cornea → pupil → lens → retina → optic nerve → LGN of
thalamus → optic radiation → occipital lobe
Melanin: black
pigment located behind the retina, which absorbs excess light not
captured by the retinal photoreceptor cells
Retina: most
posterior layer comprising photoreceptor cells rods and cones
Optic disc: retinal
blind spot due to absence of rods and cones
Rods: low-acuity
night vision; more numerous than cones
Rhodopsin →
all-trans- retinal → nerve impulse to occipital lobe
Cones: responsible
for high-acuity color vision; less numerous than rods; concentrated in
fovea centralis
Compression of the
optic chiasm (e.g., expanding pituitary adenoma) → bitemporal hemianopia
Lesions to the
optic tract → ipsilateral hemianopia
Lesions of upper
and lower divisions → ipsilateral hemianopsia with macular sparing
Massive infarct of
occipital lobe → contralateral hemianopsia without macular sparing
Pupillary light
reflex: regulates intensity of light entering the eye by controlling
pupil diameter
Shining light in
one eye: normal response is constriction of both pupils
Direct response:
constriction of pupil in eye exposed to light
Consensual
response: constriction of pupil in eye not exposed to light
Accommodation
reflex: brings nearby objects into focus
STRUCTURES
OF THE EYE - OPTICS
blind
spot - optic disc - macula - fovea - Aqueous humor - vitreous humor
photoreceptors -
Rods - Cones
Refractive
power of a lens
diopters
Refractive
errors
3
retina
uveal tract -
choroid - clllary body - iris
sclera - cornea
CORNEA
refracted -
anterior chamber - posterior chamber - vitreous body
ciliary muscles - ciliary body -
zonule fibers - accommodation
PUPIL
PHOTORECEPTION
LAYERS
OF THE RETINA
Pigment
epithelial cell layer
Bruch membrane
Photoreceptor
layer - rods and cones
phototransduction
blind spot
Outer
limiting membrane
Outer
nuclear layer
Outer
plexiform layer
bipolar
cells - horlzontal cells
Bipolar cells
Few cones synapse
on a single bipolar cell - high acuity and low sensitivity
Many rods synapse
on a single bipolar cell - less acuity greater sensitivity
Horizontal
& amacrine cells - interneurons
Inner
nuclear layer
amacrlne
cells - Muller cells
Inner
plexiform layer
Ganglion
cell layer
Optic
nerve layer - Nerve ftber layer
optic disc or optic
papllla - blind spot
Inner
llmltlng membrane
STRUCTURE
OF THE PHOTORECEPTORS
outer segments -
rhodopsin
inner segments
RODS
scotopic vision
rhodopsin
CONES
photopic vision
iodopsin
L-type
cones
M-type
cones
S-type
cones
DISTRIBUTION
OF RODS & CONES IN THE RETINA
RETINAL
SPECIALIZATION
optic disc, or
papilla - blind spot - macula lutea - fovea
STEPS
IN PHOTORECEPTION - IN THE RODS - PHOTOTRANSDUCTION CASCADE
Rhodopsin - opsin -
retinal
vitamin A-linked
photopigment (opsin)
Light
11-cis -
all-trans - photo
isomerization - metarhodopsin II
Vitamin A -
night blindness
transducin,
or Gt -
G protein transducin
phosphodiesterase
cGMP
levels decrease
closure
of Na+ channels
dark - dark current
- depolarization
light -
hyperpolarization
Hyperpolarization
decreases the
release of glutamate
types
of glutamate receptors
ionotropic
receptors are excitatory - metabotropic receptors are inhibitory -
onoff patterns
VISUAL
RECEPTIVE FIELDS
Receptive
fields of the ganglion cells and lateral geniculate cells
center of its
receptor field - surround of its receptive field
On-center,
off-surround
Off-center,
on-surround
PHOTORECEPTORS,
HORIZONTAL CELLS, & BIPOLAR CELLS
Oncenter,
offsurround
Offcenter,
onsurround
AMACRINE
CELLS
GANGLION
CELLS
LATERAL
GENICULATE CELLS OF THE THALAMUS
VISUAL
CORTEX
Simple
cells
bars of light -
position and orientation
Complex
cells
moving bars or
edges of light
Hypercomplex
cells
ength and to curves
and angles
OPTIC
PATHWAYS & LESIONS
nasal
hemiretina cross at the optic chiasm - temporal hemiretina
geniculocalcarine
tract - visual cortex
Hemianopia
third neuron - LGN
of the thalamus
BIPOLAR
CELLS
ribbon synapse -
action potentials (APs)
OFF
bipolar cells
ionotroplc
glutamate receptors.
ON
bipolar cells
metabotropic
glutamate receptor
Parallel
processing
Spatial
distribution
GANGLION
CELLS 2ND
Midget
ganglion cells
parvocellular
pathway
Parasol
ganglion cells
magnocellular
pathway
Bistratified
ganglion cells
koniocellular
pathway
OPTIC
CHIASM & OPTIC TRACT
visual field
LATERAL
GENICULATE NUCLEI
magnocellular
layers - parvocellular layers - koniocellular layers
retinotopic
organization
OPTIC
RADIATIONS
LESIONS
Cutting
Optic nerve
Cutting
Optic
chiasm
Cutting
Optic
tract
Cutting
Geniculocalcarine
tract
macular sparing
CORTICAL
PROCESSING OF VISION
PRIMARY
VISUAL CORTEX
primary vlsual
cortex (striate cortex) - calcarine sulcus in the occipital lobe -
retinotopic columns - stereopsis - 2 streams
VENTRAL
PATHWAY
temporal lobe
DORSAL
PATHWAY
parietal lobe
COLOR
VISION
L-type
cones - M·type cones - S-type cones - trichromacy
COLOR
INFORMATION PROCESSING
opponency
neurons - Red-green cells - single opponency
double opponency
Red-cyan cells
Blue-yellow cells
INFLUENCE OF COLOR
ON BEHAVIOR
OPTIC
REFLEXES
PUPILLARY
LIGHT REFLEX
Afferent
and efferent pathways
optic nerve -
optic tract - pretectal nuclei - Edinger-Westphal (E-W) nuclei -
preganglionic parasympathetic fibers - oculomotor nerve - ciliary
ganglia - constrictor pupillae muscles
Direct
versus consensual response
PUPILLODILATOR
REFLEX
posterior
hypothalamus - pregangllonlc sympathetic - sympathetic chain - supertor
cervical ganglion - carotid artery - ophthalmic division of the
trlgemlnal nerve - dllator puplllae muscle
ACCOMMODATION
converge - adduct
refractive power
- Increasing the curvature
pupils must
constrict
near triad
Afferent
& afferent pathways
primary visual
cortex - association cortex - superior colliculus and pretectal nucleus
- oculomotor nuclear complex - Edinger-Westphal
parasympathetic
innervation - constrictor pupllae muscles - ciliary muscles
Vergence
center
medial rectus
muscles
CORNEAL
BLINK REFLEX
ophthalmic
division ot the trigeminal nerve
- spinal trigeminal tract
- chief sensory nucleus of V - facial motor nucleus - orbicularis oculi
TOC
MOTOR CONTROL SYSTEMS
TOC
BASAL
GANGLIA - CONTROL OF MOVEMENT
(Krebs
LIR
2017)
V1 PDF
OVERVIEW
decision
to move
direction of
movement
amplitude of
movement
motor expression of
emotions
modulates
thalamic outflow to the motor
cortex to plan and execute smooth
movements
Many synaptic
connections are inhibitory and use GABA
as their neurotransmitter
ANATOMY
CAUDATE
NUCLEUS
PUTAMEN
striatum
GLOBUS
PALLIDUS
lentiform
NUCLEUS
ACCUMBENS
SUBTHALAMIC
NUCLEUS
SUBSTANTIA
NIGRA
CROSS-SECTIONAL
ANATOMY
ventricles
and the insula
TRACTS
INPUT
TO THE BASAL GANGLIA
integrator
OUTPUT
FROM THE BASAL GANGLIA
INTERNAL
CIRCUITS OF THE BASAL GANGLIA
tonic
inhibition - release inhibition model
direct
pathway - indirect pathway
corticostrlatal
pathway - nigrostriatal pathway
subthalamic
fasclculus - thalamic fasciculus
The
striatum communicates with the thalamus and the cerebral cortex by two
opposing pathways
Connections
between the striatum and the substantia nigra use dopamine as their
neurotransmitter
Dopamine is
inhibitory on the indirect pathway (D2 receptors) and excitatory on the
direct pathway (D1 receptors).
Thus, the action of
dopamine is, overall, excitatory
Direct
pathway is,
overall, excitatory
Indirect pathway
is, overall, inhibitory
FUNCTIONAL
RELATIONSHIPS
MOTOR
CIRCUIT
oculomotor
COGNITIVE
CIRCUIT
LIMBIC
CIRCUIT
BLOOD
SUPPLY
LESIONS
Lesions
of the globus pallidus
result in inability
to maintain postural support
Lesions
of the subthalamic nucleus
are caused by the
release of inhibition on the contralateral side
result in wild,
flinging movements (e.g., hemiballismus).
Lesions
of the striatum
are caused by the
release of inhibition
result in quick,
continuous, and uncontrollable movements
occur in patients
with Huntington disease
Lesions
of the substantia nigra
are caused by destruction of dopaminergic neurons
occur in patients
with Parkinson disease
Since dopamine
inhibits the indirect (inhibitory) pathway and excites
the direct (excitatory) pathway, destruction of dopaminergic neurons is, overall,
inhibitory
Symptoms include lead-pipe rigidity, tremor, and reduced
voluntary movement
TOC
CEREBELLUM
(Krebs
LIR
2017)
V1 PDF
OVERVIEW
coordinate and
predict - efficacy and precision
ANATOMY
vermis - folia
LOBES
anterior lobe -
posterior lobe - flocculonodular lobe
cerebellar tonsils
CEREBELLAR
DEEP NUCLEI
dentate,
emboliform, globose, and fastigial (mnemonic: don't eat greasy food)
CEREBELLAR
PEDUNCLES
CEREBELLAR
CORTEX
homunculus
TRACTS
AFFERENTS
mossy fibers -
climbing fibers
Inferior
cerebellar peduncle
Middle
cerebellar peduncle
Superior
cerebellar peduncle (SCP)
EFFERENTS
Superior
cerebellar peduncle
Inferior
cerebellar peduncle
FUNCTIONAL
RELATIONSHIPS
FEEDBACK
MECHANISM
FEED-FORWARD
MECHANISM
VESTIBULO-CEREBELLAR
CONNECTIONS
- control of balance and eye movement
archicerebellum
Afferents
and efferents
Additional
input
stability and
balance
SPINO-CEREBELLAR
CONNECTIONS
- synergy, which is control of rate, force, range, and direction of
movement
paleocerebellum
Inputs
Functions
Truncal movement -
bilateral - bilaterally
Limb
movement
CEREBRO-(PONTO)-CEREBELLAR
CONNECTIONS
- planning and initiation of movement
neocerebellum
Reciprocal
connections
dentatorubrothalamic
tract - dentatothalamic tract
Functions
Sensory consequence
Voluntary movement
Coordination of
motor activity and cognition
CYTOARCHITECTURE
OF THE CEREBELLAR CORTEX
LAYERS
Granular
layer
innermost
granule cells,
Golgi type II cells, and glomeruli
In glomeruli, axons
of mossy fibers form synaptic connections on dendrites of granular and
Golgi type II cells
Purkinje
cell layer
middle
Output is always
inhibitory
Molecular
layer
outermost
stellate and basket
cells, dendrites of Purkinje and Golgi type II cells, and parallel
fibers (axons of granule cells)
parallel fibers
synapse on dendrites of Purkinje cells, basket cells, stellate cells,
and Golgi type II cells
CONNECTIONS
Input
Climbing
fibers
a single region of
the medulla (inferior olive)
make multiple
synapses onto Purkinje cells, resulting in high-frequency bursts, or
complex spikes
“condition” the
Purkinje cells
play a role in
cerebellar motor learning
Input
Mossy
fibers
many centers in the
brain stem and spinal cord
include
vestibulocerebellar, spinocerebellar, and pontocerebellar afferents
make multiple
synapses on Purkinje fibers via interneurons
Synapses on
Purkinje cells result in simple spikes
synapse on granule
cells in glomeruli.
The axons of
granule cells bifurcate and give rise to parallel cells.
The parallel fibers
excite multiple Purkinje cells as well as inhibitory interneurons
(basket, stellate, Golgi type II)
Output
Purkinje cells are
the only
always inhibitory;
the neurotransmitter is γ-aminobutyric acid (GABA)
projects to deep
cerebellar nuclei and to the vestibular nucleus
modulates the
output of the cerebellum and regulates rate, range, and direction of
movement (synergy)
CELLS
& FIBERS OT THE CEREBELLAR CORTEX
Cells of the cerebellar cortex
granule cell
layer - parallel fibers
Fibers
of the cerebellar cortex
cerebellar
afferents
inferior olivary
nuclear complex
WIRING
OF THE CEREBELLAR CORTEX
BLOOD
SUPPLY
CLINICAL
DISORDERS OF THE CEREBELLUM—ATAXIA
result
in lack of coordination,
including delay in initiation of movement, poor execution of a sequence
of movements, and inability to perform rapid alternating movements (dysdiadochokinesia)
Intention tremor
occurs during attempts to perform voluntary movements
Rebound phenomenon
is the inability to stop a movement
TOC
INTEGRATION
OF MOTOR CONTROL
(Krebs
LIR
2017)
V1 PDF
OVERVIEW
efferent branch of
the CNS
cerebellum
receives sensory input and sends independent and segregated pathways to
the LMN system and the UMN system of the brainstem and the cortex -
coordinator and predictor
basal ganglia -
decision to move, the direction and amplitude of movement, and the motor
expression of emotions
THE
UPPER MOTOR NEURON SYSTEM
CORTICAL
MOTOR SYSTEM - MOTOR CORTEX
network of cortical
areas - precise, target oriented, and efficient - emotlonal output; and
respond to changes
Premotor
cortex and supplementary motor cortex (area 6)
generating a plan
for movement
programs complex
motor sequences and is active during “mental rehearsal” for a movement
Primary
motor cortex (area 4)
execution of
movement
Programmed patterns
of motoneurons are activated
Excitation of
upper motoneurons is transferred to the brain stem and spinal cord,
where the lower motoneurons are activated and cause voluntary movement
...
Pyramidal tracts (corticospinal and
corticobulbar) pass through the medullary pyramids
All others are extrapyramidal
tracts and originate primarily in the following structures of the
brain stem
...
VESTIBULAR
NUCLEI
postural and
movement adjustments
Lateral
vestibulospinal tract
Deiters nucleus and
projects to ipsilateral motoneurons and interneurons
powerful
stimulation of extensors and inhibition of flexors
RETICULAR
FORMATION
locomotlon and
postural control - muscle tone
Pontine
reticulospinal tract
projects to the
ventromedial
spinal cord
general stimulatory
effect on both extensors and
flexors, with the predominant effect on extensors.
Medullary
reticulospinal tract
projects to spinal cord interneurons in
the intermediate gray area.
general inhibitory
effect on both extensors and
flexors, with the predominant effect on extensors
RED
NUCLEUS
relay and
processing
Rubrospinal
tract
projects to
interneurons in the lateral spinal cord
produces
stimulation of flexors and inhibition of extensors
...
TECTOspinal
tract
superior colliculus
and projects to the cervical spinal cord
is involved in the
control of neck muscles
...
THE
LOWER MOTOR NEURON SYSTEM
final common
pathway - circuitry within the anterior horn - alpha motor neurons -
gamma motor neurons - local circuit neurons
MODULATORY
INFLUENCES ON THE MOTOR SYSTEM
BASAL
GANGLIA
CEREBELLUM
Connections
Coordination
of movement
LESIONS
TO THE MOTOR SYSTEMS
pyramidal
system and an extrapyramldal system
TOC
MEMORY, EMOTION /
MOTIVATION & HOMEOSTASIS
TOC
HYPOTHALAMUS
(Krebs
LIR
2017)
V1 PDF
OVERVIEW
thalamus
- third ventricle - diencephalon
- limbic system
- homeostasis
ANATOMY
lamina
terminalis
- mammillary bodies - posterior limb of the internal capsule
- optic chiasm - optic tracts - mammillary bodies - tuber
cinereum - infundibulum - pituitary stalk - median eminence
LATERAL &
MEDIAL ZONES
columns
of the fornix
ANTERIOR, MIDDLE
& POSTERIOR REGIONS
middle
or tuberal
AFFERENTS &
EFFERENTS
THE MEDIAL
FOREBRAIN BUNDLE AND THE DORSAL LONGITUDINAL FASCICULUS
reticular
formation
OTHER AFFERENT CONNECTIONS
General somatic, viscera!, and gustatory Information
Limbic afferents
hippocampus
- amygdala - fornix - stria terminalis and the ventral amygdalofugal
fibers
Afferents from the cortex, thalamus, and retina
orbitofrontal
and clngulate - widespread association - frontal lobe
suprachiasmatlc
nucleus (SCN)
EFFERENT CONNECTIONS
hippocampus
and amygdala - cortical structures
Descending fibers
to the brainstem and spinal cord
medial
forebrain
bundle and the dorsal longitudinal fasciculus -
periaqueductal gray (PAG) and reticular formation - parasympathetic
nuclei - sympathetic nuclei - medial zone - mammillary bodies
Ascending
fibers to the forebrain
mammillothalamic
tract - anterior nucleus of the thalamus - lateral zone - DM nucleus of
the thalamus
FUNCTIONS
REGULATION OF
ENDOCRINE FUNCTION
pituitary
gland or hypophysis - neurohypophysis - adenohypophysis
CONTROL OF THE
POSTERIOR LOBE OF THE PITUITARY
supraoptic
-
paraventricular nuclei - magnocellular cells - oxytocin -
vasopressin, or antidiuretic hormone (ADH) - hypothalamic-hypophyseal
tract - posterior lobe of the pituitary
Vasopressin
regulation
Oxytocin regulation
CONTROL OF THE
ANTERIOR LOBE OF THE PITUITARY
releaslng
or release-inhibiting (known simply as "inhibiting") honnones
The
hypothalamic-hypophyseal portal system
portal
system
Regulation of the
hypothalamic and pituitary hormones
long
feedback loops
- short feedback loops
REGULATION OF
VISCERAL FUNCTION
parasympathetic
- sympathetic
REGULATION OF
HOMEOSTATIC FUNCTIONS
TEMPERATURE REGULATION
Lesions
hyperthermia
- hypothermia - polkllothermia
Sweat glands
REGULATION OF FOOD INTAKE
Lateral hypothalamus
"hunger'
or "feeding center'
Ventrornedial hypothalamus
"satlety
center"
REGULATION OF WATER BALANCE
lateral
hypothalamus and of osmoreceptors in the anterior region induces
drinking - "thirst center" - ADH
REGULATION OF
CIRCADIAN RHYTHMS & THE SLEEP-WAKE CYCLES
Circadian rhythms
SCN
- master clock - retinohypothalamic tract - melatonin - clock - calendar
Sleep-wake cycle
narcolepsy
BLOOD SUPPLY
LESIONS
TOC
LIMBIC
(Krebs
LIR
2017)
V1 PDF
OVERVIEW
limbic
lobe - subcortlcal structures
ANATOMY
LIMBIC LOBE
parahippocampal
gyrus - cingulate gyrus - subcallosal gyrus - cingulum - subcortical structures -
hippocampus - amygdala - septal nuclei
entorhinal cortex
HYPOTHALAMUS
HIPPOCAMPUS
hippocampal
formation
- subiculum - hippocampus - Ammon horn - dentate gyrus
Fimbria
- fornix
neurogenesis
AMYGDALA
Basolateral nuclei
attaching
emotional significance to a stimulus
Central nucleus
visceral
responses to emotional stimuli
Corticomedial
nuclei
emotlonal
affective responses to food
Stria terminalis
medial
nuclei
Ventral
amygdalofugal fibers
THE SEPTAL NUCLEI
frontal
lobe - anterior commissure - medial forebrain bundle
THE EXTENDED PAPEZ
CIRCUIT OR NETWORK
hippocampus
fornix
mammlllary bodies
mammillothalamlc
tract to the anterior nucleus of the thalamus
cingulate gyrus
FUNCTIONS OF LIMBIC
SYSTEM STRUCTURES
HIPPOCAMPUS
SHORT-TERM MEMORY
working
LONG-TERM MEMORY
Explicit or
declarative memory
Episodic
memory
Semantic memory
lmplicit or
nondeclaratlve memory
Skills
and habits - Emotional memory - Conditioned reflexes
AMYGDALA
Emotional
learning and memory
implicit
memory - basolateral nucleus - hypothalamus - medial nucleus of the
thalamus - orbitofrontal cortex
amygdala is
involved in linking perception with visceral and behavioral responses
and with memory
Fear
and fear conditioning
REWARD CIRCUITRY
dopaminerglc
fibers - VTA - nucleus accumbens
ADDICTION
withdrawal
Dopamine and
saliency
Dopamine and stress
LESIONS
TOC
OLFACTION / TASTE
(Krebs
LIR
2017)
V1 PDF
Trigeminal
Chemoreception
TOC
OLFACTION
- OLFACTORY SYSTEM
Smell:
detected by olfactory receptor cells on olfactory epithelium
Axons of olfactory
receptor cells: form the first cranial nerve (CN I)
Axons of mitral
cells: form the olfactory tract/stria, which project to olfactory cortex
and amygdala
Olfactory receptor
cells: only regenerative neurons in adult human
Binding of
odoriferous molecules to cilia on olfactory cells: ultimately results
in action potential generation and transduction of signal to olfactory
cortex
OVERVIEW
receptor
neurons
- bipolar cells
OLFACTORY
EPITHELIUM
cribriform
plate
- nasal septum
Cells of the
olfactory epithelium
bipolar
neurons - olfactory knob
Basal
cells
Supporting cells
Secretory cells - Bowman
glands
Olfactory
processing and coding
primary olfactory
neurons - G protein
OLFACTORY BULB
mitral,
tufted, periglomerular, and granule cells
glomeruli
CENTRAL PROJECTIONS
OF THE OLFACTORY PATHWAY
olfactory
tract - lateral (primary) olfactory tract - uncus and entorhinal area -
limen insulae - arnygdala - piriform area
anterior olfactory
nucleus - anterior commissure
Downstream
relays of the olfactory cortex
secondary
olfactory cortex
TOC
TASTE
- GUSTATORY SYSTEM
Taste
buds on anterior two thirds of tongue: detect sweet and salty tastes;
transmit through lingual nerve to facial nerve
Taste buds on
posterior third of tongue: detect bitter and sour tastes; transmit
through glossopharyngeal and vagus nerves
OVERVIEW
TASTE
BUDS
taste pore - taste
receptor cells
Fungiform
papillae
chorda tympani
Foliate
papillae
Circumvallate
papillae
SIGNAL
TRANSDUCTION FOR TASTE
Type
I cells
Receptor (type II)
Presynaptic (type
III)
Sour
Salty
Sweet
Bitter
Umami
Signal
transduction In type II receptor cells
NEURONAL
PATHWAYS FOR TASTE
solitary
tract - solitary nucleus - ventral postero medial nucleus or the
thalamus - postcentral gyrus - insula
TRIGEMINAL
CHEMORECEPTION
Polymodal
C fibers
TOC
PAIN
(Krebs
LIR
2017)
V1 PDF
OVERVIEW
NOCICEPTORS
NOCICEPTIVE
FIBERS
A delta fibers and
C fibers - glutamate, substance P, and calcitonin gene-related peptide
(CGRP) -
"silent" nociceptors
NOCICEPTOR
ACTIVATION
membrane
depolarization
Temperature
TRPV1 receptor -
capsaicin - transient receptor potendal (TRP) channels - menthol
TRPMB receptor
Mechanical
activation
Chemical
activation
inflammation
SENSITIZATION
OF PERIPHERAL RECEPTORS
bradykinin &
prostaglandins
Activation
threshold
hyperalgesia -
allodynia
Silent
nociceptors
PAIN
PROCESSING IN THE SPINAL CORD
Synaptic
targets
nociceptive-specific
(NS) - wide dynamic range (WDR)
Neurotransmitters
Wide dynamic range
neurons - Wind-up
Wind-up
Substance
P and CGRP
Increased
excitation
Sensitization
ASCENDING
NOCICEPTIVE PATHWAYS
thalamus -
spinothalamic tract - anterolateral system
lateral
sensory-discriminative component - medial affective-motivational
component
LATERAL
SENSORY-DISCRIMINATIVE PATHWAY
neospinothalamlc
tract - Adelta fibers - anterior white commlssure
- somatosensory cortex - ''first" pain
MEDIAL AFFECTIVE-MOTIVATIONAL PATHWAYS
reticular
formation, midbrain, thalamus, hypothalamus, and limbic system -
"second" pain
Spinornesencephalic
tract
periaqueductal gray
(PAG) and the superior colllculus
Spinoreticular
tract
noradrenergic
locus ceruleus and the serotonerglc raphe nuclel as well as to the
rostral anteromedial medulla, an area that is particularly rich in
opioid receptors
Paleospinothalamic
tract
dorsomedial -
intralaminar - nuclei of the thalamus
Other
tracts
neuroendocrlne and
visceral
CORTICAL
PAIN MATRIX
mirror neuron
system
LATERAL
PAIN SYSTEM
primary and
secondary somatosensory cortices
MEDIAL
PAIN SYSTEM
anterior cingulate
cortex (ACC), lnsula, amygdala, and hypothalamus
SALIENCY
salient sensory
input - withdrawal reflex
PAIN
MODULATION
pain inhibition -
descending inhibition - descending facilitation
GATE
CONTROL THEORY OF PAIN
local circuit
interneurons - inhibitory
DESCENDING
INFLUENCES FROM THE BRAINSTEM
PAG and the
reticular formation - locus ceruleus and the raphe nuclei
Descending
cortical input
Nociceptlve
modulation
salience filter
ENDOGENOUS
OPIOID SYSTEM
pain matrix -
medial pain system - descending brainstem systems - posterior horn ot
the spinal cord - enkephalins, endorphins, and dynorphins
Opioid
receptors
mu delta kappa -
hyperpolarization - peripheral nerves
Descending
inhibition
enkephalin
receptors - circuit neurons - PAG - rostral anteromedial medulla
CHRONIC
PAIN
CHRONIC
NOCICEPTIVE PAIN
CHRONIC
NEUROPATHIC PAIN
hyperalgesia
- allodynia - Summation - paresthesias - dysesthesias
perlpheral and
central syndromes, complex pain disorders (such as complex regional pain
syndrome), and mixed pain syndromes
MALADAPTIVE
PERIPHERAL SENSITIZATION
disinhibition - hyperalgesia -
allodynia
GLIAL
SIGNALING
Astroglia
Microglia
LESIONS
THERAPY
TOC
HIGHER
FUNCTIONS OF THE NERVOUS SYSTEM
BLOOD
SUPPLY, BLOOD–BRAIN BARRIER & CEREBROSPINAL FLUID (CSF)
LEARNING
MEMORY & INSTINCT
THIRST &
HUNGER
SEXUAL
NEUROENDOCRINOLOGY
VIGILANCE &
MOOD
STRESS &
EMOTION
TOC
SOFTWARES OF HUMAN
THOUGHT & ACTION
(Baillet
Précis de Physiologie 1992) Dramatis personæ
- Backup
TOC
VALUES
TOC
EQUATIONS
TOC
REFERENCES
PHYSIOLOGY
NEUROPSYCHOPHYSIOLOGY
PHYSIOLOGY
AUTHORS
Tellingen. Organ
Physiology from a Phenomenological Point of View. 1e. 2003. [ Bolk's Companions ] [
Info
& Download
]
Ward. Physiology at
a Glance. 4e. 2017.
Le.
First Aid USMLE Step 1. 34e. 2024.
Le.
First Aid Basic Sciences. 3e. 2017.
Silbernagl.
Color Atlas of Physiology. 7e. 2015. [
Download
]
Costanzo.
How
to Study Physiology “Succeeding in Physiology”. [ PDF - PPT - YouTube
]
Costanzo.
BRS Physiology. 8e. 2022.
7e. 2018.
[ 344 pages
] [
Download 7e
] [
Download 7e ]
Costanzo.
Physiology. 7e. 2021. 6e.
2017. [ 516 pages
]
[
Download
6e ]
Costanzo.
BRS Physiology Cases & Problems. 4e. 2012.
Mulroney.
Netter' s Physiology Flash Cards. 2e. 2015.
[ 450 pages
] [
Download
]
Preston.
LIR Physiology. 3e. 2024. 2e.
2019. [ 590 pages
]
Preston.
LIR
Flash
Cards Physiology.1e. 2014. [ 420 pages
]
Brown. Rapid Review Physiology. 2e.
2011. [ 288 pages
]
[
Download
]
[
Amazon
] [
Read
]
Bullock. NMS Physiology. 4e. 2001. [
Read
3e
]
Dudek.
HY Physiology. 1e. 2007.
Kibble. Big Picture Physiology. 1e.
2009.
Rhoades. Medical Physiology.
Boron. Medical Physiology.
Berne.
Physiology.
Guyton. Physiology. 12e. 2010.
Caratini.
Tout en 1. Corps Humain.
1994.
Caratini. Panorama Sciences. Biologie. Neurobiologie. 1993.
Caratini. Encyclopédie. Médecine.
Physiologie.
Caratini. Collection. Médecine.
Physiologie.
Martin. Physiologie Humaine Appliquée.
2e. 2017. [ 900 pages
]
[
Download
]
[
Amazon
] [
Read
]
Baillet.
Précis de Physiologie Humaine. 1992. [ Tome 1 Texte
928 pages, Tome 2 Figures 624 pages
]
[ Livre qui date
un peu mais reste le meilleur ! ]
Baillet. Logiciels Humains,
Grille
Biosophique
-
Dramatis Personæ
Baillet. Nouveaux Propos de la
Chaisière. 1976. [
Comment
& Pourquoi étudier la Physiologie ] [
PDF ]
Baillet. Examen critique et
raisonné des
philosophes contemporains, de leur vie doctrines et opinions. 1999. [
Critique ]
Baillet.
De retour de Babel une histoire Biosophique du Primate humain. 2003.
Baillet.
L'horreur est humaine. 2013. [
Info PDF ]
Baillet. Etude & Amitié. [
PDF ]
Baillet. Human Values, Aesthetics & Detribalisation. [
PDF ]
Demarez. Des fatalités de la tribu
française. L'Histoire au regard de la Biologie. [
La grille biosophique, décodeur universel ]
[
PDF ]
Jack Baillet [
Wikipedia
]
https://www.cairn.info/revue-natures-sciences-societes-2019-2-page-125.htm#
https://www.babelio.com/livres/Chamak-Le-groupe-des-10/306053
UNSORTED
https://externat-medecine.fr/meilleurs-livres-physiologie/
https://5livres.fr/meilleurs-livres-physiologie-humaine/
https://physoc.onlinelibrary.wiley.com/
TOPICS
OVERVIEW
https://en.wikipedia.org/wiki/Outline_of_physiology
CARDIOVASCULAR
https://en.wikipedia.org/wiki/Cardiovascular_physiology
MATHEMATICAL
https://people.maths.ox.ac.uk/fowler/courses/physiol/physiolnotes.pdf
OTHER TOPICS
COMPUTATIONAL PHYSIOLOGY & MODELLING
COMPUTER SIMULATIONS
MATHEMATICAL MODELS
STATISTICAL MODELS
INTEGRATIVE
AGEING
& DEGENERATION
COMPARATIVE
PHYSIOLOGY
DEVELOPMENT
AND REGENERATION
EVOLUTIONARY
PHYSIOLOGY
GENOMICS & PROTEOMICS
INHERITANCE
TRANSCRIPTION & TRANSLATION
METABOLIC
PATHWAYS
REGULATORY
PATHWAYS
SIGNALLING
PATHWAYS
METABOLISM : PLACES
LIVER
NUTRITION
METABOLISM
: FLOWS & MOMENTS
ENVIRONMENTAL
ALTITUDE
GRAVITY
THERMOREGULATION
TOXINS, POLLUTANTS AND CHEMICAL AGENTS
EXERCISE
AEROBIC
EXERCISE
ANAEROBIC
EXERCISE
ATHLETES
ENDURANCE
AND PERFORMANCE
EXERCISE
METABOLISM
INJURY,
STRESS AND FATIGUE
NEWS
NEUROPSYCHOPHYSIOLOGY &
NEUROSCIENCE
AUTHORS
Krebs. LIR Neuroscience. 2e. 2017.
[ 480 pages
]
[
Download
]
Weyhenmeyer.
Rapid Review Neuroscience. 1e. 2006.
Greenstein. Color atlas of neuroscience. 1e. 2000.
[
Download
]
Vilis. [ Courses ]
[ The Physiology of the Senses ]
[ My Brain Notes for Medical Students ]
[ Survival Skills for Graduate Students ]
Vibert. Neurophysiologie : De la
physiologie à l'exploration fonctionnelle. 3e. 2019. [ 320 pages
]
https://fr.wikibooks.org/wiki/Neurosciences
TOPICS
NEWS
https://www.tf1info.fr/sciences-et-innovation/des-scientifiques-suisses-decouvrent-un-nouveau-type-de-cellule-dans-le-cerveau-humain-2269130.html
https://www.nature.com/articles/s41586-023-06502-w
CEREBRAL CORTEX
(Glasser,
2016)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990127/
(Salehi,
2020)
https://www.sciencedirect.com/science/article/pii/S1053811919309577#bib25
SENSORY
(Delmas,
2011)
http://web.as.uky.edu/Biology/faculty/cooper/Bio450-AS300/Presentations%20on%20proprioception/Molecular%20mechanisms%202011.pdf
VISION
Journal of Vision (" Be Free, Be Everywhere, Be Forever ")
Webvision (The Organization of the Retina and
Visual System)
DICTIONARIES,
GLOSSARIES, ENCYCLOPEDIAS
LINK
LISTS, RESOURCE LISTS, ORGANIZATIONS
NEUROBIOLOGY
NEUROANATOMY
NON-PRIMATE NEUROANATOMY
PRIMATE NEUROANATOMY
HUMAN NEUROANATOMY
NEUROHISTOLOGY
NEUROPSYCHOPHYSIOLOGY
CELLULAR
SLEEP
http://www.nature.com/nrn/posters/sleep/index.html
SPEECH
SENSES
AUDITORY
CHEMICAL
MIND
COGNITIVE SCIENCE
CONSCIOUSNESS,
PHILOSOPHY
PSYCHOLOGY
BEHAVIOR
ILLUSIONS, SENSORY PHENOMENA, SYNESTHESIA
LEARNING THEORY
SOFTWARES OF HUMAN THOUGHT AND ACTION
Dramatis_Personæ
NEUROPATHOLOGY
PSYCHOPATHOLOGY
NEUROLOGY
PSYCHIATRY
PSYCHOANALYSIS
CONDITIONS
AFFECTIVE
ALZHEIMER
http://www.alz.org/
http://www.healthcommunities.com/alzheimers-disease/overview-of-alzheimers.shtml
http://www.nia.nih.gov/alzheimers
http://www.alzforum.org/
AUTISM SPECTRUM
http://www.ninds.nih.gov/disorders/asperger/asperger.htm
EPILEPSY
MULTIPLE SCLEROSIS
NEUROPSYCHOPHARMACOLOGY
COMPUTING
CS, IT, AI
TECHNIQUES
MICROSCOPY
NEUROIMAGING
VIRTUAL REALITY, 3D, SL, OS, VRML
NIH VIDEOCASTING & PODCASTING
http://videocast.nih.gov/PastEvents.asp?c=16
https://www.youtube.com/user/nihvcast/search?query=neuroscience
NATURE
http://www.nature.com/neuro/index.html
http://www.nature.com/nrn/index.html
http://www.nature.com/nrn/posters/index.html
NEUROIMMUNOLOGY
http://www.nnjournal.net/
SENSORY
CELLS & NEUROPHYSIOLOGY
MOTOR
ATTENTION
MEMORY
CONSCIOUSNESS & HIGHER FUNCTION
APPLIED
ANS
CONTROL OF HOMEOSTASIS
NERVOUS SYSTEM PATHOPHYSIOLOGY
NEURAL CIRCUITS
CELLULAR/MOLECULAR
DEVELOPMENT/PLASTICITY/REPAIR
SYSTEMS/CIRCUITS
NEUROBIOLOGY OF DISEASE
NEUROHISTOLOGY
NEUROEMBRYOLOGY
NEUROPATHOLOGY
NEUROIMAGING
NEUROPSYCHOPHARMACOLOGY
INNOVATIVE METHODOLOGY
https://nba.uth.tmc.edu/neuroscience/toc.htm
https://www.bna.org.uk/resources/#educational-resources
https://www.brainfacts.org/3D-Brain#intro=true
UNSORTED
http://videocast.nih.gov/PastEvents.asp?c=16
http://faculty.washington.edu/chudler/neurok.html
http://braininfo.rprc.washington.edu/
http://www.bristol.ac.uk/synaptic/
http://www.jneurosci.org/
http://www.slideshare.net/elsavonlicy/brodmann
COGNITIVE & BEHAVIOURAL NEUROSCIENCE
DEVELOPMENTAL NEUROSCIENCE
MOTOR CONTROL
NEURAL CIRCUITS & SYSTEMS
NEUROLOGICAL CONDITIONS, DISORDERS & TREATMENTS
NEURONAL PLASTICITY & REPAIR
STRUCTURAL NEUROSCIENCE
MORE REFERENCES
TOC
NEWS & UPDATES
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