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Physiology & Neuroscience - Physiologie - Fisiologia

SIMPLE CONTENTS

NEWS & UPDATES
MAPS
OVERVIEW
CELLULAR
MUSCULO-SKELETAL
CARDIO-VASCULAR
RESPIRATORY
RENAL
GASTRO-INTESTINAL
METABOLISM
LIVER
NUTRITION
ENDOCRINE
REPRODUCTIVE
ACID BASE BALANCE
SODIUM & WATER BALANCE, FLUID COMPARTIMENTS
NEURO-PSYCHO-PHYSIOLOGY & NEUROSCIENCE
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

NEURO-PSYCHO-PHYSIOLOGY & 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

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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

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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

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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

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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)

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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

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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

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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

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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

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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

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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

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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

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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

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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)

SENSE OF TOUCH
MEISSNER tactile bodies light touch
MERKEL discs sustained touch
PACINIAN corpuscles vibration
FNE pain when stimulated strongly, and itching when stimulated less strongly
PERITRICHAL NERVES without myelin sheaths around the hair follicles that are activated upon stroking and caressing
RUFFINI = BULBOUS corpuscles located in the skin around the nails that respond to firm pressure and transmit our sense of grip. They also play a role in our sense of warmth
KRAUSE corpuscles that transmit cold stimuli

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 & NEUROSCIENCE

PHYSIOLOGY

REF PHYSIOLOGY
DIDACTIC & GENERAL PHYSIOLOGY

Tellingen. Organ Physiology from a Phenomenological Point of View. 1e. 2003. [ Bolk's Companions ] [ 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. 3e. 2016. 1312 pages

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 ]
https://fr.scribd.com/document/411416953/Physiologie-Humaine-Appliqu-e
https://pdfcoffee.com/physiologie-humaine-appliqu-e-3-pdf-free.html

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

REF PHYSIOLOGY
OVERVIEW

https://en.wikipedia.org/wiki/Outline_of_physiology

REF PHYSIOLOGY
CELL PHYSIOLOGY

REF PHYSIOLOGY
MUSCLE

REF PHYSIOLOGY
RESPIRATION

REF PHYSIOLOGY
EXERCISE AND WORK PHYSIOLOGY
AEROBIC EXERCISE
ANAEROBIC EXERCISE
ATHLETES
ENDURANCE AND PERFORMANCE
EXERCISE METABOLISM
INJURY, STRESS AND FATIGUE

REF PHYSIOLOGY
CARDIOVASCULAR

https://en.wikipedia.org/wiki/Cardiovascular_physiology

REF PHYSIOLOGY
RENAL, ELECTROLYTES AND ACID-BASE PHYSIOLOGY

MATHEMATICAL

https://people.maths.ox.ac.uk/fowler/courses/physiol/physiolnotes.pdf

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

NEWS

UNSORTED

https://externat-medecine.fr/meilleurs-livres-physiologie/
https://5livres.fr/meilleurs-livres-physiologie-humaine/
https://physoc.onlinelibrary.wiley.com/

NEURO-PSYCHO-PHYSIOLOGY & NEUROSCIENCE

REF NEUROPHYSIOLOGY
DIDACTIC 

Bos. Consciousness, the Brain, & Free Will. A Phenomenological Perspective. 1e. 2024. [ 274 pages ] [ Bolk's Companions ] [ Download ]

Barker. Neuroanatomy & Neuroscience at a Glance. 5e. 2017. [ 192 pages ] [ Cf Anatomy ]
Barker. Neuroscience : an illustrated guide. 1991. 292 pages [ Cf Neuroanatomy at a Glance ]
https://archive.org/details/neuroscienceillu0000bark/mode/1up

Krebs. LIR Neuroscience. 2e. 2017. [ 480 pages ] [ Download ]

Weyhenmeyer. Rapid Review Neuroscience. 1e. 2006. 307 pages
https://archive.org/details/neuroscience0000weyh

Greenstein. Color atlas of neuroscience. 1e. 2000. 723 pages [ Download ]

Vilis. https://www.tutis.ca/index.htm [ 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://ia802902.us.archive.org/25/items/neurophysiologie_202003/Neurophysiologie.pdf

https://en.wikibooks.org/wiki/Neuroscience
https://fr.wikibooks.org/wiki/Neurosciences

Kandel. Principles of Neural Science. 6e. 2021. 1696 pages
https://www.amazon.co.uk/Principles-Neural-Science-MEDICAL-DENISTRY-dp-1259642232/dp/1259642232/ref=dp_ob_title_bk
Contents https://neurology.mhmedical.com/book.aspx?bookid=3024#254327318
5e https://ia601508.us.archive.org/34/items/PrinciplesOfNeuralScienceFifthKANDEL/Principles%20of%20Neural%20Science%2C%20Fifth%20-%20KANDEL.pdf

Bear M, Paradiso M, Connon BW. Neuroscience: Exploring the Brain. 4e. Baltimore: Lippincott Williams 8t Wilkins; 2020.  975 pages
https://www.zlibrary.to/dl/neuroscience-exploring-the-brain
https://psv4.userapi.com/s/v1/d/utcQErqUieZPpH8AY1wH2vhPEy9MgATow2wh3eQhqxvhUPb137xlceNG9M5kzBkOyatEgLvm1Lm801bCkufRawMkfza2dbf-Kd6c36xBXmOUK46Z/NeuExpTheBra4thEdi.pdf

SOFTWARES OF HUMAN THOUGHT AND ACTION

Baillet. Logiciels Humains, Grille Biosophique - Dramatis Personæ
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 ]

NEWS

REF NEUROPHYSIOLOGY
OVERVIEW

https://nba.uth.tmc.edu/neuroscience/toc.htm

https://www.thehighestofthemountains.com/

LeDoux, Joseph E. 2003.
Synaptic Self: How Our Brains Become Who We Are.
New York, NY: Penguin Books.

Lewin, R. 1980.
"Is Your Brain Really Necessary?”
Science (New York, N.Y.) 210(4475):1232-34.
doi: 10.1126/science.7434023.
Lorber, J. 1983. "Is your brain really necessary?" in Hydrocephalus im frühen Kindesalter: Fortschritte der Grundlagenforschung,
https://www.lemonde.fr/blog/realitesbiomedicales/2021/08/10/lhomme-a-la-tete-presque-vide/
https://med.virginia.edu/perceptual-studies/wp-content/uploads/sites/360/2017/12/Discrepancy-between-cerebral-structure-and-cognitive-functioning-JNMD.pdf

Jaschke, Artur C. 2021.
Mind the Music: on music, improvisation and the brain.
HetMoet-Menard Press.
https://research.vu.nl/ws/portalfiles/portal/77024101/complete+dissertation.pdf

REF NEUROPHYSIOLOGY
ANATOMICAL & FUNCTIONAL ORGANIZATION : OVERVIEW

Babcock, Loren E., and Richard A. Robison. 1989.
“Preferences of Palaeozoic Predators.”
Nature 337(6209):695-96. doi:10.1038/337695c0.
https://www.academia.edu/34623333/Preferences_of_Palaeozoic_predators?auto=download

McGilchrist, Iain. 2021.
The Matter with Things: Our Brains, Our Delusions, and the Unmaking of the World.
London: Perspectiva Press. [ Download ]
https://en.wikipedia.org/wiki/The_Matter_with_Things

Taylor, Joseph J., Christopher Lin, Daniel Talmasov, Michael A. Ferguson, Frederic L. W. V. J. Schaper, Jing Jiang, Madeleine Goodkind, Jordan Grafman, Amit Etkin, Shan H. Siddiqi, and Michael D. Fox. 2023.
“A Transdiagnostic Network for Psychiatric Illness Derived from Atrophy and Lesions.”
Nature Human Behaviour. doi: 10.1038/ s41562-022-01501-9.

Sur, Mriganka, Alessandra Angelucci, and Jitendra Sharma. 1999.
'Rewiring Cortex: The Role of Patterned Activity in Development and Plasticity of Neocortical Circuits'.
Journal of Neurobiology 41(1):33-43. doi: 10.1002/(SICI)1097- 4695(199910)41:1<33::AID-NEU6>3.0.CO;2-1.

Roe AW, Pallas SL, Kwon YH, Sur M.
Visual projections routed to the auditory pathway in ferrets: receptive fields of visual neurons in primary auditory cortex.
J Neurosci. 1992;12(9):3651-3664. doi:10.1523/JNEUROSCI.12-09-03651.1992

Noë, Alva. 2010.
Out of Our Heads: Why You Are Not Your Brain, and Other Lessons from the Biology of Consciousness.
1. paperback ed. New York, NY: Hill & Wang. [ Download ]

Mountcastle, Vernon B. 1957.
Modality and Topographic Properties of Single Neurons of Cat's Somatic Sensory Cortex.
Journal of Neurophysiology 20(4):408-34. doi: 10.1152/jn.1957.20.4.408.

Kandel 2018
https://dokumen.pub/the-disordered-mind-what-unusual-brains-tell-us-about-ourselves-0374287864-9780374287863.html

Paul, R. L., H. Goodman, and M. Merzenich. 1972.
Alterations in Mechanoreceptor Input to Brodmann's Areas 1 and 3 of the Postcentral Hand Area of Macaca Mulatta after Nerve Section and Regeneration.
Brain Research 39(1):1-19. doi: 10.1016/0006-8993(72)90782-2.

Head, W. H. R., and Henry Rivers. 1908.
A Human Experiment in Nerve Division.

REF NEUROPHYSIOLOGY
ANATOMICAL & FUNCTIONAL ORGANIZATION : CEREBRAL CORTEX

https://en.wikipedia.org/wiki/Yakovlevian_torque

Glasser, M., Coalson, T., Robinson, E. et al.
A multi-modal parcellation of human cerebral cortex.
Nature 536, 171–178 (2016). https://doi.org/10.1038/nature18933
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990127/

Salehi, M., Greene, A. S., Karbasi, A., Shen, X., Scheinost, D., & Constable, R. T. (2020).
There is no single functional atlas even for a single individual: Functional parcel definitions change with task.
NeuroImage, 208, 116366.
https://www.sciencedirect.com/science/article/pii/S1053811919309577#bib25

Bos, Arie. 2017.
Thinking Outside the Brain Box: Why Humans Are Not Biological Computers.
Translated by Philip Mees. Floris Books.

Bos, Arie. 2018.
Use your brain!
Netherlands. Christofoor Publishing.

Sano F.
The Convolutional Pattern of the Brains of Identical Twins, a Study on the Hereditary Resemblance in the Furrows of the Cerebral Hemispheres.
Philos. Transac. Of the Royal Soc. B. 1916.

Ramachandran, V. S. 2011.
The Tell-Tale Brain: A Neuroscientist's Quest for What Makes Us Human.
1st ed. New York: W.W. Norton. [ Download ]
https://pmc.ncbi.nlm.nih.gov/articles/PMC3148743/
https://www.zora.uzh.ch/id/eprint/67368/1/The_tell-tale_brain.pdf

REF NEUROPHYSIOLOGY
ANATOMICAL & FUNCTIONAL ORGANIZATION : BBB VENTRICULES CSF MENINGES

Bieri, G., Schroer, A.B. & Villeda, S.A.
Blood-to-brain communication in aging and rejuvenation.
Nat Neurosci 26, 379–393 (2023). https://doi.org/10.1038/s41593-022-01238-8
https://www.nature.com/articles/s41593-022-01238-8?s=09

Møllgård, Kjeld, Felix R. M. Beinlich, Peter Kusk, Leo M. Miyakoshi, Christine Delle, Virginia Plá, Natalie L. Hauglund, Tina Esmail, Martin K. Rasmussen, Ryszard S. Gomolka, Yuki Mori, and Maiken Nedergaard. 2023.
A Mesothelium Divides the Subarachnoid Space into Functional Compartments.
Science (New York, N.Y.) 379(6627):84-88. doi: 10.1126/science.adc8810.
https://pubmed.ncbi.nlm.nih.gov/36603070/
https://www.statnews.com/wp-content/uploads/2024/02/madness-24-36.pdf

ANATOMICAL & FUNCTIONAL ORGANIZATION : FUNCTIONAL NETWORKS OVERVIEW

Barrett, Lisa Feldman. 2018.
How Emotions Are Made: The Secret Life of the Brain.
First Mariner Book edition. Boston New York: Mariner Books.
https://archive.org/details/how-emotions-are-made-the-secret-life-of-the-brain-by-lisa-feldman
https://dokumen.pub/how-emotions-are-made-the-secret-life-of-the-brain-0544133315-9780544133310.html

Barrett.
https://lisafeldmanbarrett.com/

ANATOMICAL & FUNCTIONAL ORGANIZATION : NETWORKS DMN

https://en.wikipedia.org/wiki/Default_mode_network

https://www.insb.cnrs.fr/fr/cnrsinfo/un-nouveau-modele-du-reseau-cerebral-du-mode-par-defaut

Alves, P.N., Foulon, C., Karolis, V. et al.
An improved neuroanatomical model of the default-mode network reconciles previous neuroimaging and neuropathological findings.
Commun Biol 2, 37  (2019).
https://doi.org/10.1038/s42003-019-0611-3

Raichle, Marcus E., Ann Mary MacLeod, Abraham Z. Snyder, William J. Powers, Debra A. Gusnard, and Gordon L. Shulman. 2001.
A Default Mode of Brain Function.
Proceedings of the National Academy of Sciences 98(2):676-82.
doi: 10.1073/pnas.98.2.676.
https://www.biorxiv.org/content/10.1101/148890v2.full.pdf

ANATOMICAL & FUNCTIONAL ORGANIZATION : NETWORKS SN ECN

Menon, Vinod, and Lucina Q. Uddin. 2010.
“Saliency, Switching, Attention and Control: A Network Model of Insula Function.”
Brain Structure & Function 214(5-6):655-67.
doi: 10.1007/s00429-010-0262-0.

Menon, Vinod. 2011.
Large-Scale Brain Networks and Psychopathology: A Unifying Triple Network Model.
Trends in Cognitive Sciences 15(10):483-506.
doi: 10.1016/j.tics.2011.08.003.

ANATOMICAL & FUNCTIONAL ORGANIZATION : NETWORKS 6 MAJORS SOMATO MOTOR DORSAL ATTENTION VISUAL

Buckner, Randy L., and Fenna M. Krienen. 2013.
The Evolution of Distributed Association Networks in the Human Brain.
Trends in Cognitive Sciences 17(12):648-65.
doi:10.1016/j.tics.2013.09.017.

Van den Heuvel, M. P. 2011.
“The Connected Brain.”
Neuropraxis 15(1):3-14.
doi: 10.1007/s12474-011-0002-0.

Van den Heuvel, Martijn P., Karina J. Kersbergen, Marcel A. de Reus, Kristin Keunen, René S. Kahn, Floris Groenendaal, Linda S. de Vries, and Manon J. N. L. Benders. 2015.
'The Neonatal Connectome During Preterm Brain Development'.
Cerebral Cortex (New York, N.Y.: 1991) 25(9):3000-3013.
doi: 10.1093/cercor/bhu095.
https://pubmed.ncbi.nlm.nih.gov/24833018/

Van den Heuvel
https://www.dutchconnectomelab.nl/
Mapping the human connectome - https://www.youtube.com/watch?v=XVN_dGXUzFs

ANATOMICAL & FUNCTIONAL ORGANIZATION : SPINAL CORD & PERIPHERAL NERVOUS SYSTEM

ANATOMICAL & FUNCTIONAL ORGANIZATION : ANS

Riganello, F., Vatrano, M., Cortese, M.D. et al.
Central autonomic network and early prognosis in patients with disorders of consciousness.
Sci Rep 14, 1610 (2024).
https://doi.org/10.1038/s41598-024-51457-1
https://www.nature.com/articles/s41598-024-51457-1/figures/1

ANATOMICAL & FUNCTIONAL ORGANIZATION : HEART BRAIN

Armour, J. A. 2003.
Neurocardiology. Anatomical and Functional Principles.
Boulder Creek, California: Institute of Heart Math.
https://neuroimaginalinstitute.com/wp-content/uploads/2013/03/Neurocardiology.pdf
https://pmc.ncbi.nlm.nih.gov/articles/PMC4945716/
https://physoc.onlinelibrary.wiley.com/cms/asset/3f7d6ffa-8111-4e1a-8f18-ac9ec251a832/tjp7337-fig-0001-m.jpg
https://en.wikipedia.org/wiki/Ganglionated_plexi

Muqtadar, Hurmina, Fernando D. Testai, and Philip B. Gorelick. 2012.
 “The Dementia of Cardiac Disease.”
Current Cardiology Reports 14(6):732-40. doi: 10.1007/s11886-012-0304-8.
https://pubmed.ncbi.nlm.nih.gov/22968344/

Bruggemans, E. F. 2013.
“Cognitive Dysfunction after Cardiac Surgery: Pathophysiological Mechanisms and Preventive Strategies.”
Netherlands Heart Journal 21(2):70-73. doi: 10.1007/s12471-012-0347-x.
https://pubmed.ncbi.nlm.nih.gov/23184600/

ANATOMICAL & FUNCTIONAL ORGANIZATION : GUT BRAIN ENS

Kaelberer, Melanie Maya, Kelly L. Buchanan, Marguerita E. Klein, Bradley B. Barth, Marcia M. Montoya, Xiling Shen, and
Diego V. Bohórquez. 2018.
“A Gut-Brain Neural Circuit for Nutrient Sensory Transduction.”
Science (New York, N.Y.) 361(6408):eaat5236. doi: 10.1126/science.aat5236.
https://pubmed.ncbi.nlm.nih.gov/30237325/
https://www.science.org/doi/10.1126/science.aat5236?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed#Fa

Hsiao, Elaine Y., Sara W. McBride, Sophia Hsien, Gil Sharon, Embriette R. Hyde, Tyler McCue, Julian A. Codelli, Janet Chow, Sarah E. Reisman, Joseph F. Petrosino, Paul H. Patterson, and Sarkis K. Mazmanian. 2013.
“Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders.”
Cell 155(7):1451-63. doi: 10.1016/j.cell.2013.11.024.

Willyard, Cassandra. 2021.
“How Gut Microbes Could Drive Brain Disorders.”
Nature 590(7844):22-25. doi: 10.1038/ d41586-021-00260-3.

Foos, I. 2020.
“In Search of the ADHD Bacterium.”
New Scientist 75:47.

Cryan, John F., and Timothy G. Dinan. 2012.
“Mind-Altering Microorganisms: The Impact of the Gut Microbiota on Brain and Behaviour.”
Nature Reviews. Neuroscience 13(10):701-12. doi: 10.1038/nrn3346.

Mu, Chunlong, Yuxiang Yang, and Weiyun Zhu. 2016.
“Gut Microbiota: The Brain Peacekeeper.
Frontiers in Microbiology.7:345. doi: 10.3389/fmicb.2016.00345.

Hadhazy, Adam. 2010.
“Think Twice: How the Gut's "Second Brain" Influences Mood and Well-Being.”
Feb 12, 2010. Scientific American. Accessed Dec. 7, 2021 (https://www.scientificamerican.com/article/gut-second-brain/).

Luczak, Hania. 2000.
“How the Belly Influences the Head.”
Geo Magazin. Nr. 11. S.137-146.

Blom, J. 2002.
“More and more known about nervous system in gut.”
Nutrition magazine, 12-13.

ANATOMICAL & FUNCTIONAL ORGANIZATION : VAGUS NERVE

De Couck, Marijke. 2015.
“The role of the vagus nerve in cancer.”
Free University, Brussels.

Kibleur, Astrid, Sonia Pellissier, Valérie Sinniger, Jade Robert, Eloise Gronlier, Didier Clarençon, Laurent Vercueil, Dominique Hoffmann, Bruno Bonaz, and Olivier David. 2018. “Electroencephalographic Correlates of LowFrequency Vagus Nerve Stimulation Therapy for Crohn's Disease.” Clinical Neurophysiology 129(5):1041-46. doi: 10.1016/j. clinph.2018.02.127.

Clark, Kevin B., Dean K. Naritoku, Douglas C. Smith, Ronald A. Browning, and Robert A. Jensen. 1999.
“Enhanced Recognition Memory Following Vagus Nerve Stimulation in Human Subjects.”
Nature Neuroscience 2(1):94-98. doi: 10.1038/4600.

Tracey, Kevin J. 2002.
“The Inflammatory Reflex.”
Nature 420(6917):853-59. doi: 10.1038/nature01321.
https://www.researchgate.net/publication/10983143_The_inflammatory_reflex
https://pubmed.ncbi.nlm.nih.gov/12490958/

REF NEUROPHYSIOLOGY
CELLS & NEUROPHYSIOLOGY : OVERVIEW

Libet, Benjamin. 2006.
“Reflections on the Interaction of the Mind and Brain.”
Progress in Neurobiology 78(3-5):322-26.
doi: 10.1016/j.pneurobio.2006.02.003.
https://pubmed.ncbi.nlm.nih.gov/16675090/
https://hps.elte.hu/Basler/Courses/Consciousness/Libet/Libet%20article.pdf
https://www.francoisloth.com/lultime-dualisme-de-benjamin-libet/
https://en.wikipedia.org/wiki/Benjamin_Libet
https://orbi.uliege.be/bitstream/2268/70041/1/DUBOIS_DANIEL-ACTA-SYSTEMICA-VOL-X-No-1-2010.pdf
[ We cannot describe consciousness in terms of the physical domain ]

Hagihara, Takuma, Hiroaki Mano, Tomohiro Miura, Mitsuyasu Hasebe, and Masatsugu Toyota. 2022.
“Calcium Mediated Rapid Movements Defend against Herbivorous Insects in Mimosa Pudica.”
Nature Communications 13(1):6412. doi: 10.1038/s41467-022-34106-x.

CELLS & NEUROPHYSIOLOGY : NEUROHISTOLOGY

Herculano-Houzel, Suzana. 2016.
The Human Advantage: A New Understanding of How Our Brain Became Remarkable.
The MIT Press.
https://archive.org/details/humanadvantagene0000herc

S. Herculano-Houzel,
The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost,
Proc. Natl. Acad. Sci. U.S.A. 109 (supplement_1) 10661-10668,
https://doi.org/10.1073/pnas.1201895109 (2012).
https://www.pnas.org/doi/full/10.1073/pnas.1201895109

Herculano-Houzel.
https://www.ted.com/talks/suzana_herculano_houzel_what_is_so_special_about_the_human_brain?language=fr-ca&subtitle=en

Suzana Herculano-Houzel - The costs and benefits of gaining associative neurons in brain evolution. 2023.
https://www.youtube.com/watch?v=w4KoFUUxTQw

Herculano-Houzel.
https://www.youtube.com/@suzanaherculano

Barrington, E. J. W. 1970. Invertebrate Structure and Function. London: Nelson.

Yeo, Michele, Ken Berglund, Michael Hanna, Junjie U. Guo, Jaya Kittur, Maria D. Torres, Joel Abramowitz, Jorge Busciglio, Yuan Gao, Lutz Birnbaumer, and Wolfgang B. Liedtke. 2013. “Bisphenol A delays the perinatal chloride shift in cortical neurons by epigenetic effects on the Kcc2 promoter.”
Proceedings of the National Academy of Sciences 110(11):4315-20. doi: 10.1073/pnas.1300959110.
https://pubmed.ncbi.nlm.nih.gov/23440186/

https://en.wikipedia.org/wiki/Interneuron

NEUROGLIAL CELLS

ASTROCYTES

de Ceglia, R., Ledonne, A., Litvin, D.G. et al.
Specialized astrocytes mediate glutamatergic gliotransmission in the CNS.
Nature 622, 120–129 (2023). https://doi.org/10.1038/s41586-023-06502-w
https://pubmed.ncbi.nlm.nih.gov/37674083/
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

NEUROGENESIS

Gadye, Levi. 2015.
“Born Again Brains.”
Vice. Accessed Sept. 27, 2022 (https://www.vice.com/en/article/ jp53gg/born-again-brains).
https://www.vice.com/en/article/born-again-brains/

Moreno-Jiménez, Elena P., Miguel Flor-García, Julia Terreros-Roncal, Alberto Rábano, Fabio Cafini, Noemí Pallas-Bazarra, Jesús Ávila, and María Llorens-Martín. 2019.
“Adult Hippocampal Neurogenesis Is Abundant in Neurologically Healthy Subjects and Drops Sharply in Patients with Alzheimer's Disease.”
Nature Medicine 25(4):554-60. doi: 10.1038/s41591-019-0375-9.
https://pubmed.ncbi.nlm.nih.gov/30911133/
https://bohrium.dp.tech/paper/arxiv/817346413280100353

TRANSMITTERS : GLUTAMATE GABA ACETYLCHOLINE

https://en.wikipedia.org/wiki/Template:Receptor_modulators

GLUTAMATE

Uemura, Takuya, Masakazu Hachisu, Yoshitake Desaki, Ayaka Ito, Ryosuke Hoshino, Yuka Sano, Akira Nozawa, Kadis Mujiono, Ivan Galis, Ayako Yoshida, Keiichirou Nemoto, Shigetoshi Miura, Makoto Nishiyama, Chiharu Nishiyama, Shigeomi Horito, Tatsuya Sawasaki, and Gen-Ichiro Arimura. 2020.
“Soy and Arabidopsis Receptor-like Kinases Respond to Polysaccharide Signals from Spodoptera Species and Mediate Herbivore Resistance.”
Communications Biology 3(1):224. doi: 10.1038/s42003-020-0959-4.
https://pubmed.ncbi.nlm.nih.gov/32385340/
[ Glutamate appears to activate an electrical signal in some plants that moves forward linearly, as in an axon ]

GABA

https://en.wikipedia.org/wiki/GABA

https://en.wikipedia.org/wiki/%CE%93-Hydroxybutyric_acid

ACETYLCHOLINE

MODULATORS : PEPTIDES AMINES HORMONES

DOPAMINE

SEROTONIN

Dehue, Trudy. 2010.
The Depression Epidemic - On the duty to take destiny into your own hands.
Amsterdam: AtlasContact.
https://metzelf.nl/m-boekbesprekingen/the-depression-epidemic/?lang=en
https://www.academia.edu/45589769/The_New_Art_of_Living_Towards_a_logic_of_peace_and_well_being_for_a_more_value_oriented_and_happy_life

Special Issue: The Future of the History of Psychology
https://psycnet.apa.org/fulltext/2016-35747-001.html
https://www.researchgate.net/publication/305522091_The_Future_of_the_History_of_Psychology_Revisited

Dehue, Trudy. 2016.
“The Missing Substance in the Brain.”
De Groene Amsterdammer, February 3.

https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor

Touw, D. J., & Neef, C. (1991).
WHO'S AFRAID OF SEROTONIN?
Pharmaceutisch Weekblad, 126(20), 477.
https://research.rug.nl/en/publications/whos-afraid-of-serotonin

Andrews, Paul W., Aadil Bharwani, Kyuwon R. Lee, Molly Fox, and J. Anderson Thomson. 2015.
“Is Serotonin an Upper or a Downer? The Evolution of the Serotonergic System and Its Role in Depression and the Antidepressant Response.”
Neuroscience and Biobehavioral Reviews 51:164-88.
doi: 10.1016/j.neubiorev.2015.01.018.
https://pubmed.ncbi.nlm.nih.gov/25625874/
https://www.docdroid.net/qbj8/andrews2015-pdf
https://www.jandersonthomson.com/wp-content/uploads/2023/09/Andrews_et_al_serotonin_upper2015_NBR-1.pdf
https://www.sciencedaily.com/releases/2015/02/150217114119.htm

Moncrieff, Joanna, Ruth E. Cooper, Tom Stockmann, Simone Amendola, Michael P. Hengartner, and Mark A. Horowitz. 2022.
“The Serotonin Theory of Depression: A Systematic Umbrella Review of the Evidence.”
Molecular Psychiatry.
doi: 10.1038/s41380-022-01661-0.
https://pubmed.ncbi.nlm.nih.gov/35854107/

Moncrieff, J., Cooper, R.E., Stockmann, T. et al.
The serotonin hypothesis of depression: both long discarded and still supported?.
Mol Psychiatry 28, 3160–3163 (2023).
https://doi.org/10.1038/s41380-023-02094-z

Daut, Rachel A., and Laura K. Fonken. 2019.
“Circadian Regulation of Depression: A Role for Serotonin.”
Frontiers in Neuroendocrinology 54:100746.
doi: 10.1016/j.yfrne.2019.04.003.

Salvan, P., Fonseca, M., Winkler, A.M. et al.
Serotonin regulation of behavior via large-scale neuromodulation of serotonin receptor networks.
Nat Neurosci 26, 53–63 (2023).
https://doi.org/10.1038/s41593-022-01213-3
https://pmc.ncbi.nlm.nih.gov/articles/PMC9829536/

TESTOSTERONE

https://en.wikipedia.org/wiki/Testosterone

https://www.wikiwand.com/en/articles/testosterone

Eisenegger, C., M. Naef, R. Snozzi, M. Heinrichs, and E. Fehr. 2010.
“Prejudice and Truth About the Effect of Testosterone on Human Bargaining Behaviour.”
Nature 463(7279):356-59.
doi: 10.1038/nature08711.
https://pubmed.ncbi.nlm.nih.gov/19997098/
[ Testosterone affects behavior, but contrary to popular belief, it does not promote aggression. In fact, testosterone specifically seems to increase with a rise in status (thus as a secondary effect) and enhances cooperation skills, and avoidance of quarreling and intimidating ]

Eisenegger C, Haushofer J, Fehr E (June 2011).
"The role of testosterone in social interaction".
Trends in Cognitive Sciences. 15 (6): 263–71.
doi:10.1016/j.tics.2011.04.008.
PMID 21616702. S2CID 9554219.
https://www.zora.uzh.ch/id/eprint/58008/1/Testosterone_social_interaction_revision_%2812_Apr_11%29.pdf
[ In humans, testosterone appears more to promote status-seeking and social dominance than simply increasing physical aggression.
When controlling for the effects of belief in having received testosterone, women who have received testosterone make fairer offers than women who have not received testosterone ]

PSYCHO-NEURO-IMMUNOLOGY PNI

Lena Bourhy.
Impact du sepsis sur les circuits neuronaux et le comportement à long-terme.
Neurobiologie. Université Paris Cité, 2021. Français. NNT : 2021UNIP5198. tel-04621807
https://theses.hal.science/tel-04621807v1/file/va_Bourhy_Lena.pdf

La psycho-neuro-immunologie existe-t-elle ? Par Gabriel Gachelin 1992
https://shs.cairn.info/revue-francaise-de-psychosomatique-2003-1-page-67?lang=fr

Davis, Daniel M. 2020.
Immune About the role of our immune system in fighting disease.
Amsterdam: Nieuwezijds.

Davis, Daniel M. 2018.
How studying the immune system leads us to new medicines
The Lancet, Volume 391, Issue 10136, 2205 - 2206

Hayashi, Takashi, Satoru Tsujii, Tadao Iburi, Tamiko Tamanaha, Keiko Yamagami, Rieko Ishibashi, Miyo Hori, Shigeko Sakamoto, Hitoshi Ishii, and Kazuo Murakami. 2007.
“Laughter Up-Regulates the Genes Related to NK Cell Activity in Diabetes.”
Biomedical Research 28(6):281-85. doi: 10.2220/biomedres.28.281.

Capel, Pierre Jean Antoine. 2019.
The Emotional DNA: Feelings don’t exist, they emerge.
K.pl Education.

Cousins, Norman. 1979.
Anatomy of an illness as perceived by the patient: reflections on healing and regeneration.
New York: Norton

Van Gool, W. A. 2000.
“The effect of rivastigmine in Alzheimer's disease.”
Ge-Bu. Medicines Bulletin 34(2):17-22.

PLASTICITY & REPAIR

PLASTICITY : BIOCHEMICAL ASPECTS

https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter)
https://en.wikipedia.org/wiki/NMDA_receptor
https://en.wikipedia.org/wiki/AMPA
https://en.wikipedia.org/wiki/AMPA_receptor
https://en.wikipedia.org/wiki/Long-term_potentiation

PLASTICITY : LEARNING, MEMORY, AND THE ROLE OF RNA

Kandel, Eric R. 2018. The deranged mind: what unusual brains tell us about ourselves. Amsterdam: Atlas Contact.

Bédécarrats, Alexis, Shanping Chen, Kaycey Pearce, Diancai Cai, and David L. Glanzman. 2018.
“RNA from Trained Aplysia Can Induce an Epigenetic Engram for Long-Term Sensitization in Untrained Aplysia.”
Eneuro 5(3):ENEURO.0038-18.2018. doi: 10.1523/ENEURO.0038-18.2018
https://pubmed.ncbi.nlm.nih.gov/29789810/

Fuchs, Thomas. 2008. Das Gehirn - ein Beziehungsorgan: eine phänomenologisch-ökologische Konzeption. 1. Aufl. Stuttgart: Kohlhammer.

Thomas Fuchs, Écologie du cerveau. La phénoménologie et la biologie de l'esprit incarné Presses universitaires d'Oxford, 2018, 334 pages
Thomas Fuchs, Ecology of the Brain. The Phenomenology and Biology of the Embodied Mind, Oxford University Press, 2018, 334 pages
https://journals.openedition.org/alter/694?lang=de

PLASTICITY IN PRACTICE

Scholz, Jan, Miriam C. Klein, Timothy E. J. Behrens, and Heidi Johansen-Berg. 2009.
“Training Induces Changes in White Matter Architecture.”
Nature Neuroscience 12(11):1370-71. doi: 10.1038/nn.2412.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2770457/

Yeatman, Jason D., Robert F. Dougherty, Michal Ben-Shachar, and Brian A. Wandell. 2012.
“PNAS Plus: Development of white matter and reading skills.”
Proceedings of the National Academy of Science 109:E3045-53. doi: 10.1073/pnas.1206792109.

Bick, Johanna, Tong Zhu, Catherine Stamoulis, Nathan A. Fox, Charles Zeanah, and Charles A. Nelson. 2015.
"Effect of Early Institutionalization and Foster Care on Long-Term White Matter Development: A Randomized Clinical Trial".
JAMA Pediatrics 169(3):211. doi: 10.1001/jamapediatrics.2014.3212.

Gerhardt, Sue. 2015.
Why Love Matters: how affection shapes a baby's brain.
Second edition. New York, NY: Routledge.

Ianniruberto, A., and E. Tajani. 1981.
“Ultrasonographic Study of Fetal Movements.”
Seminars in Perinatology 5(2):175-81.

Hadders-Algra, M., and T. Dirks. 2000.
“The motor skills of the fetus and newborn.”
Pp. 11-22 in Baby’s Motor Development: Varying, selecting, learning to adapt, edited by M. Hadders-Algra and T. Dirks. Houten: Bohn Stafleu van Loghum.

Liu, Tina T., Adrian Nestor, Mark D. Vida, John A. Pyles, Christina Patterson, Ying Yang, Fan Nils Yang, Erez Freud, and Marlene Behrmann. 2018.
“Successful Reorganization of Category-Selective Visual Cortex Following Occipito-Temporal Lobectomy in Childhood.”
Cell Reports 24(5):1113-1122.e6. doi: 10.1016/j.celrep.2018.06.099.

Doidge, Norman. 2008.
The Brain That Changes Itself: Stories of Personal Triumph from the Frontiers of Brain Science.
London: Penguin Books.

Aguilar, M.J.
“Recovery of Motor Function after Unilateral Infarction of the Basis Pontis; Record of A Case.”
Am. Journ. of Physical Medicine & Rehabilitation 48, 6: 279-288, December 1969.

Arrowsmith-Young, Barbara. 2012.
The woman who changed her brain: How I Left My Learning Disability Behind and Other Stories of Cognitive Transformation.
1st ed. New York City: Free Press.

Wang, Chao, Huimin Yue, Zhechun Hu, Yuwen Shen, Jiao Ma, Jie Li, Xiao-Dong Wang, Liang Wang, Binggui Sun, Peng Shi, Lang Wang, and Yan Gu. 2020.
“Microglia Mediate Forgetting via Complement-Dependent Synaptic Elimination.”
Science 367(6478):688-94. doi: 10.1126/science.aaz2288.
[ how synapses are eliminated : by the brain's immune cells ]

MEMORY

TWO TYPES OF MEMORY

Kitamura, Takashi, Sachie K. Ogawa, Dheeraj S. Roy, Teruhiro Okuyama, Mark D. Morrissey, Lillian M. Smith, Roger L. Redondo, and Susumu Tonegawa. 2017.
”Engrams and Circuits Crucial for Systems Consolidation of a Memory.”
Science 356(6333):73-78. doi: 10.1126/science.aam6808.
https://pubmed.ncbi.nlm.nih.gov/28386011/
https://pmc.ncbi.nlm.nih.gov/articles/PMC5493329/

Clark, Kevin B., Dean K. Naritoku, Douglas C. Smith, Ronald A. Browning, and Robert A. Jensen. 1999.
“Enhanced Recognition Memory Following Vagus Nerve Stimulation in Human Subjects.”
Nature Neuroscience 2(1):94-98. doi: 10.1038/4600.

Pin-Chun Chen, Lauren N. Whitehurst, Mohsen Naji, Sara C. Mednick
Autonomic/Central Coupling Boosts Working Memory in Healthy Young Adults
bioRxiv 2020.04.22.056481; doi: https://doi.org/10.1101/2020.04.22.056481
Now published in Neurobiology of Learning and Memory doi: 10.1016/j.nlm.2020.107267
https://www.biorxiv.org/content/10.1101/2020.04.22.056481v1.full

MEMORY : FORGETTING

Akers, Katherine G., Alonso Martinez-Canabal, Leonardo Restivo, Adelaide P. Yiu, Antonietta De Cristofaro, Hwa-Lin Liz Hsiang, Anne L. Wheeler, Axel Guskjolen, Yosuke Niibori, Hirotaka Shoji, Koji Ohira, Blake A. Richards, Tsuyoshi Miyakawa, Sheena A. Josselyn, and Paul W. Frankland. 2014.
'Hippocampal Neurogenesis Regulates Forgetting during Adulthood and Infancy'.
Science (New York, N.Y.) 344(6184):598-602. doi: 10.1126/science.1248903.
https://pubmed.ncbi.nlm.nih.gov/24812394/

https://en.wikipedia.org/wiki/Hyperthymesia

Shafy, Samiha. 2008.
“The Science of Memory: An Infinite Loop in the Brain.”
Der Spiegel, November 21.
https://www.spiegel.de/international/world/the-science-of-memory-an-infinite-loop-in-the-brain-a-591972.html

Ally, Brandon A., Erin P. Hussey, and Manus J. Donahue. 2013.
'A Case of Hyperthymesia: Rethinking the Role of the Amygdala in Autobiographical Memory'.
Neurocase 19(2):166-81. doi: 10.1080/13554794.2011.654225.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3432421/

MEMORY & NETWORKS

Monge, Zachary A., Erik A. Wing, Jared Stokes, and Roberto Cabeza. 2018.
“Search and Recovery of Autobiographical and Laboratory Memories: Shared and Distinct Neural Components.”
Neuropsychologia 110:44-54. doi: 10.1016/j.neuropsychologia.2017.07.030.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5785570/

MIRROR NEURONS

https://en.wikipedia.org/wiki/Mirror_neuron

Mirror neurons: still an open question?
Edited by PAOLO B. Pascolo. 2013.
http://www.progressneuroscience.com/pdf/vol_1_n_1_2013/PiN_Neurotopics_2013_Pascolo.pdf
http://www.progressneuroscience.com/index/vol_1_n_1-4_2013.htm

MIRROR NEURONS : IMITATION

MIRROR NEURONS APPEAR AFTER BIRTH

ACTION OBSERVATION NETWORK

Gardner, T., N. Goulden, and E. S. Cross. 2015.
“Dynamic Modulation of the Action Observation Network by Movement Familiarity.”
Journal of Neuroscience 35(4):1561-72. doi: 10.1523/JNEUROSCI.2942-14.2015.
https://www.researchgate.net/publication/271596619_Dynamic_Modulation_of_the_Action_Observation_Network_by_Movement_Familiarity

Sgandurra, Giuseppina, Laura Biagi, Leonardo Fogassi, Elisa Sicola, Adriano Ferrari, Andrea Guzzetta, Michela Tosetti, and Giovanni Cioni. 2018.
“Reorganization of the Action Observation Network and Sensory-Motor System in Children with Unilateral Cerebral Palsy: An FMRI Study.”
Neural Plasticity 2018:1-15. doi: 10.1155/2018/6950547.

Lesourd Mathieu. 2023.
Action Observation Network Activity Related to Object-Directed and Socially-Directed Actions in Adolescents
https://web.archive.org/web/20240421055740/https://lnc.univ-amu.fr/fr/doc/hal-04307818/_22
https://web.archive.org/web/20240415132414/https://hal.science/hal-04307818

Gazzola, Valeria, Henk van der Worp, Theo Mulder, Bruno Wicker, Giacomo Rizzolatti, and Christian Keysers. 2007.
“Aplasics Born without Hands Mirror the Goal of Hand Actions with Their Feet.”
Current Biology: CB 17(14):1235- .40. doi: 10.1016/j.cub.2007.06.045.

REF NEUROPHYSIOLOGY
SENSORY SYSTEMS : OVERVIEW

Keller, Helen Adams. 1933. Helen Keller in Scotland: A Personal Record Written by Herself. Methuen, London.
Keller, Helen, Louise Stuart, and John Albert Macy. 2005. The Story of My Life. Amsterdam: World Library.
https://digital.library.upenn.edu/women/keller/life/life.html

Bronfman, Zohar Z., Simona Ginsburg, and Eva Jablonka. 2016.
“The Transition to Minimal Consciousness through the Evolution of Associative Learning”
Frontiers in Psychology 7. doi: 10.3389/fpsyg.2016.01954.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5177968/
https://www.worldscientific.com/doi/abs/10.1142/S2705078521500168

Edelman, Gerald M., and Giulio Tononi. 2001.
A Universe of Consciousness: How Matter Becomes Imagination.
1st paper- back ed., [Nachdr.]. New York, NY: Basic Books
https://en.wikipedia.org/wiki/A_Universe_of_Consciousness

Philip Ball
“How Life Works”
(2023 University of Chicago Press)
https://philipball.co.uk/how-life-works-a-users-guide-to-the-new-biology/

https://en.wikipedia.org/wiki/Damasio%27s_theory_of_consciousness

SENSORY SYSTEMS : SENSE OF TOUCH

Delmas, P., Hao, J. & Rodat-Despoix, L.
Molecular mechanisms of mechanotransduction in mammalian sensory neurons.
Nat Rev Neurosci 12, 139–153 (2011). https://doi.org/10.1038/nrn2993
https://pubmed.ncbi.nlm.nih.gov/21304548/
http://web.as.uky.edu/Biology/faculty/cooper/Bio450-AS300/Presentations%20on%20proprioception/Molecular%20mechanisms%202011.pdf

Vallbo, A., H. Olausson, J. Wessberg, and U. Norrsell. 1993.
“A System of Unmyelinated Afferents for Innocuous Mechanoreception in the Human Skin.”
Brain Research 628(1-2):301-4. doi: 10.1016/0006-8993(93)90968-s.
https://pubmed.ncbi.nlm.nih.gov/8313159/

Husserl, Edmund. 1973. Ding und Raum: Vorlesungen 1907. Edited by U. Claesges. The Hague: Nijhoff.

Cazala, Fadwa, Nicolas Vienney, and Serge Stoléru. 2015.
“The Cortical Sensory Representation of Genitalia in Women and Men: A Systematic Review.”
Socioaffective Neuroscience & Psychology 5(1):26428. doi: 10.3402/snp.v5.26428.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4357265/
https://pmc.ncbi.nlm.nih.gov/articles/PMC4357265/pdf/SNP-5-26428.pdf

Gordon, Evan M., Roselyne J. Chauvin, Andrew N. Van, Aishwarya Rajesh, Ashley Nielsen, Dillan J. Newbold, Charles J. Lynch, Nicole A. Seider, Samuel R. Krimmel, Kristen M. Scheidter, Julia Monk, Ryland L. Miller, Athanasia Metoki, David F. Montez, Annie Zheng, Immanuel Elbau, Thomas Madison, Tomoyuki Nishino, Michael J. Myers, Sydney Kaplan, Carolina Badke D'Andrea, Damion V. Demeter, Matthew Feigelis, Julian S. B. Ramirez, Ting Xu, Deanna M. Barch, Christopher D. Smyser, Cynthia E. Rogers, Jan Zimmermann, Kelly N. Botteron, John R. Pruett, Jon T. Willie, Peter Brunner, Joshua S. Shimony, Benjamin P. Kay, Scott Marek, Scott A. Norris, Caterina Gratton, Chad M. Sylvester, Jonathan D. Power, Conor Liston, Deanna J. Greene, Jarod L. Roland, Steven E. Petersen, Marcus E. Raichle, Timothy O. Laumann, Damien A. Fair, and Nico U. F. Dosenbach. 2023.
“A Somato-Cognitive Action Network Alternates with Effector Regions in Motor Cortex.”
Nature 1-9. doi: 10.1038/s41586-023-05964-2.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10172144/
https://pmc.ncbi.nlm.nih.gov/articles/PMC10172144/figure/Fig4/
[The interrupted homunculus, an integrate–isolate model of action and motor control.]
https://scitechdaily.com/hidden-linkages-scientists-find-mind-body-connection-is-built-into-brain/
https://www.sciencedaily.com/releases/2023/04/230419125052.htm
https://www.biorxiv.org/content/10.1101/2022.10.26.513940v1

Paré, Michel et al.
“Paucity of presumptive ruffini corpuscles in the index finger pad of humans.”
The Journal of comparative neurology vol. 456,3 (2003): 260-6. doi:10.1002/cne.10519
https://onlinelibrary.wiley.com/doi/10.1002/cne.10519

Cobo, R.; García-Piqueras, J.; Cobo, J.; Vega, J.A.
The Human Cutaneous Sensory Corpuscles: An Update.
J. Clin. Med. 2021, 10, 227. https://doi.org/10.3390/jcm10020227
https://www.mdpi.com/2077-0383/10/2/227

SENSORY SYSTEMS :  PREDICTING

Bastian, Amy J. 2006.
“Learning to Predict the Future: The Cerebellum Adapts Feedforward Movement Control.”
Current Opinion in Neurobiology 16(6):645-49. doi: 10.1016/j.conb.2006.08.016.
https://pubmed.ncbi.nlm.nih.gov/17071073/

SENSORY SYSTEMS : INTEROCEPTION

Wölfle, Ute, Floriana A. Elsholz, Astrid Kersten, Birgit Haarhaus, Walter E. Müller, and Christoph M. Schempp. 2015.
“Expression and Functional Activity of the Bitter Taste Receptors TAS2R1 and TAS2R38 in Human Keratinocytes.”
Skin Pharmacology and Physiology 28(3):137-46. doi: 10.1159/000367631.
https://pubmed.ncbi.nlm.nih.gov/25573083/

Wölfle, Ute, Floriana A. Elsholz, Astrid Kersten, Birgit Haarhaus, Udo Schumacher, and Christoph M. Schempp. 2016.
“Expression and Functional Activity of the Human Bitter Taste Receptor TAS2R38 in Human Placental Tissues and JEG-3 Cells.”
Molecules 21(3):306. doi: 10.3390/molecules21030306.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6273027/

Yates, Darran. 2013.
“Sensing Nutrients from Within.”
Nature Reviews Neuroscience 14(1):5-5. doi: 10.1038/nrn3420.
https://www.nature.com/articles/nrn3420

Miyamoto, T., Slone, J., Song, X., & Amrein, H. (2012).
A fructose receptor functions as a nutrient sensor in the Drosophila brain.
Cell, 151(5), 1113–1125. https://doi.org/10.1016/j.cell.2012.10.024
https://pmc.ncbi.nlm.nih.gov/articles/PMC3509419/

Lee, Robert J., Guoxiang Xiong, Jennifer M. Kofonow, Bei Chen, Anna Lysenko, Peihua Jiang, Valsamma Abraham, Laurel Doghramji, Nithin D. Adappa, James N. Palmer, David W. Kennedy, Gary K. Beauchamp, Paschalis-Thomas Doulias, Harry Ischiropoulos, James L. Kreindler, Danielle R. Reed, and Noam A. Cohen. 2012.
“T2R38 Taste Receptor Polymorphisms Underlie Susceptibility to Upper Respiratory Infection.”
The Journal of Clinical Investigation 122(11):4145-59. doi: 10.1172/JCI64240.

Lee, Robert J., Jennifer M. Kofonow, Philip L. Rosen, Adam P. Siebert, Bei Chen, Laurel Doghramji, Guoxiang Xiong, Nithin D. Adappa, James N. Palmer, David W. Kennedy, James L. Kreindler, Robert F. Margolskee, and Noam A. Cohen. 2014.
“Bitter and Sweet Taste Receptors Regulate Human Upper Respiratory Innate Immunity.”
Journal of Clinical Investigation 124(3):1393-1405. doi: 10.1172/JCI72094.

Feldman-Barrett, Lisa. 2018. How Emotions Are Made: The Secret Life of the Brain. First Mariner Book edition. Boston New York: Mariner Books.

McGilchrist, Iain. 2021. The Matter with Things: Our Brains, Our Delusions, and the Unmaking of the World. London: Perspectiva Press

Bastuji, Hélène, Stéphanie Mazza, Caroline Perchet, Maud Frot, François Mauguiere, Michel Magnin, and Luis GarciaLarrea. 2012.
“Filtering the reality: Functional dissociation of lateral and medial pain systems during sleep in humans.”
Human Brain Mapping 33(11):2638-49. doi: 10.1002/hbm.21390.

SENSORY SYSTEMS : WHERE DO WE FEEL PAIN ? xxxxxxxxxxx

SENSORY SYSTEMS : PROPRIOCEPTION

SENSORY SYSTEMS : SENSE OF BALANCE

SENSORY SYSTEMS : SENSE OF SMELL

SENSORY SYSTEMS : SENSE OF TASTE
The receptors and cells for mammalian taste. 2006.
https://web.archive.org/web/20110722041026/https://wiki.brown.edu/confluence/download/attachments/1444406/nature05401.pdf

SENSORY SYSTEMS : SENSE OF SIGHT VISION
Journal of Vision  (" Be Free, Be Everywhere, Be Forever ")
Webvision (The Organization of the Retina and Visual System)

SENSORY SYSTEMS :THERMOCEPTION OR SENSE OF TEMPERATURE

HEARING

SENSE OF LANGUAGE AND MUSIC

SENSE OF MEANING OR COMPREHENSION

COGNITION

REF NEUROPHYSIOLOGY
MOTOR SYSTEMS

BASAL GANGLIA

http://www.scholarpedia.org/article/Models_of_basal_ganglia
https://eprints.whiterose.ac.uk/107033/1/Redgrave%20Neuroscience%201999%20preprint.pdf

CEREBELLUM

https://upload.wikimedia.org/wikiversity/en/0/02/The_Cerebellum.pdf

http://www.scholarpedia.org/article/Cerebellum

Kochiyama, Takanori, Naomichi Ogihara, Hiroki C. Tanabe, Osamu Kondo, Hideki Amano, Kunihiro Hasegawa, Hiromasa Suzuki, Marcia S. Ponce de León, Christoph P. E. Zollikofer, Markus Bastir, Chris Stringer, Norihiro Sadato, and Takeru Akazawa. 2018.
Reconstructing the Neanderthal Brain Using Computational Anatomy.
Scientific Reports 8(1):6296. doi: 10.1038/s41598-018-24331-0.
https://pubmed.ncbi.nlm.nih.gov/29700382/

HYPOPHYSIS

https://wis-wander.weizmann.ac.il/life-sciences/there%E2%80%99s-new-hypothesis-your-hypophysis

AGING

Aleman, André. 2014.
Our Ageing Brain: how our mental capacities develop as we grow older.
Scribe UK. [ Read ]

PATHOLOGY NEUROLOGY & PSYCHIATRY
PSYCHOPATHOLOGY
PSYCHOANALYSIS

PATHOLOGY : OVERVIEW

Kandel, Eric R. 2018. The Disordered Mind: What Unusual Brains Tell Us About Ourselves. New York: Farrar, Straus and Giroux. [ Download ]

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

CONSCIOUSNESS & HIGHER FUNCTION

Alexander, Eben. 2017.
Living in a mindful universe: a neurosurgeon's journey into the heart of consciousness.
Emmaus, Pennsylvania: Rodale. [ Download ]

NEURO-PSYCHO-PHARMACOLOGY

UNSORTED

http://www.nature.com/neuro/index.html
http://www.nature.com/nrn/index.html
http://www.nature.com/nrn/posters/index.html
https://www.youtube.com/user/nihvcast/search?query=neuroscience
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
https://www.ncbi.nlm.nih.gov/books/NBK583710/
https://www.nature.com/articles/s41586-023-05964-2
https://neurosciencenews.com/brain-enzyme-switch-21940/
https://www.brainfacts.org/
https://nba.uth.tmc.edu/neuroscience/toc.htm
https://www.bna.org.uk/resources/#educational-resources
https://www.brainfacts.org/3D-Brain#intro=true

ATTENTION
CONTROL OF HOMEOSTASIS
NEURAL CIRCUITS
CELLULAR/MOLECULAR
DEVELOPMENT/PLASTICITY/REPAIR
SYSTEMS/CIRCUITS
NEUROIMAGING
INNOVATIVE METHODOLOGY
NEUROBIOLOGY
SLEEP
SPEECH
CHEMICAL
MIND
COGNITIVE SCIENCE
CONSCIOUSNESS, PHILOSOPHY
PSYCHOLOGY
BEHAVIOR
ILLUSIONS, SENSORY PHENOMENA, SYNESTHESIA
LEARNING THEORY
AFFECTIVE
COGNITIVE & BEHAVIOURAL NEUROSCIENCE
DEVELOPMENTAL NEUROSCIENCE
NEURAL CIRCUITS & SYSTEMS
STRUCTURAL NEUROSCIENCE
COMPUTING
CS, IT, AI
TECHNIQUES
MICROSCOPY
NEUROIMAGING
VIRTUAL REALITY, 3D, SL, OS, VRML

AUTHORS

MORE REFERENCES

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