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Physiology Review A work in Progress
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National Boards Part I Physiology section Neurophysiology (23%)
Membrane potentials, action potentials, synpatic transmission Motor function Sensory function Autonomic function Higher cortical function Special senses
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National Boards Part I Physiology (cont) Muscle physiology (14%)
Cardiac muscle Skeletal muscle Smooth muscle Cardiovascular physiology (17%) Cardiac mechanisms Eletrophysiology of the heart Hemodynamics Regulation of circulation Circulation in organs Lymphatics Hematology and immunity
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National Boards Part I Physiology (cont) Respiratory physiology (10%)
Mechanics of breathing Ventilation, lung volumes and capacities Regulation of respiration O2 and CO2 transportation Gaseous Exchange Body Fluids and Renal physiology (11%) Regulation of body fluids Glomerular filtration Tubular exchange Acid-base balance
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National Boards Part I Physiology (cont)
Gastrointestinal physiology (10%) Ingestion Digestion Absorption Regulation of GI function Reproductive physiology (4%) Endocrinology (8%) Secretion of hormones Action of hormones Regulation Exercise and Stress Physiology (3%)
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Weapons in neurophysiologist’s armory
Recording Individual neurons Gross potentials Brain scans Stimulation Lesions Natural lesions Experimental lesions
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Neurophysiology Membrane potential
Electrical potential across the membrane Inside more negative than outside High concentration of Na+ outside cell High concentration of K+ inside cell PO4= SO4= Protein Anions trapped in the cell create negative internal enviiornment
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Membrane physiology Passive ion movement across the cell membrane
Concentration gradient High to low Electrical gradient Opposite charges attract, like repel Membrane permeability Action potential Pulselike change in membrane permeability to Na+, K+, (Ca++)
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Membrane physiology In excitable tissue an action potential is a pulse like in membrane permeability In muscle permeability changes for: Na+ at onset of depolarization, during repolarization Ca++ K+ at onset of depolarization, during repolarization
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Passive ion movement across cell
If ion channels are open, an ion will seek its Nerst equilibrium potential concentration gradient favoring ion movement in one direction is offset by electrical gradient
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Resting membrane potential (Er)
During the Er in cardiac muscle, fast Na+ and slow Ca++/Na+ are closed, K+ channels are open. Therefore K+ ions are free to move, and when they reach their Nerst equilibrium potential, a stable Er is maintained
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Na+/K+ ATPase (pump) The Na+/K+ pump which is energy dependent operates to pump Na+ out & K+ into the cardiac cell at a ratio of 3:2 therefore as pumping occurs, there is net loss of one + charge from the interior each cycle, helping the interior of the cell remain negative the protein pump utilizes energy from ATP
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Ca++ exchange protein In the cardiac cell membrane is a protein that exchanges Ca++ from the interior in return for Na+ that is allowed to enter the cell. The function of this exchange protein is tied to the Na+/K+ pump if the Na+/K+ pump is inhibited, function of this exchange protein is reduced & more Ca++ is allowed to accumulate in the cardiac cell contractile strength.
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Action potential Pulselike change in membrane permeability to Na+, K+, (Ca++) Controlled by “gates” Voltage dependent Ligand dependent Depolarization Increased membrane permeability to Na+ (Ca++) Na+ influx Repolarization Increased membrane permeability to K+ K+ efflux
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Refractory Period Absolute Relative
During the Action Potential (AP), cell is refractory to further stimulation (cannot be restimulated) Relative Toward the end of the AP or just after repolarization a stronger than normal stimulus (supranormal) is required to excite cell
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All-or-None Principle
Action potentials are an all or none phenomenon Stimulation above threshold may cause an increased number of action potentials but will not cause a greater action potential
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Propagation Action potentials propagate (move along) as a result of local currents produced at the point of depolarization along the membrane compared to the adjacent area that is still polarized Current flow in biologic tissue is in the direction of positive ion movement or opposite the direction of negative ion movement
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Conduction velocity Proportional to the diameter of the fiber
Without myelin 1 micron diameter = 1 meter/sec With myelin Accelerates rate of axonal transmission 6X and conserves energy by limiting depolarization to Nodes of Ranvier Saltatory conduction-AP jumps internode to internode 1micron diameter = 6 meter/sec
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Synapes Specialized junctions for transmission of impulses from one nerve to another Electrical signal causes release of chemical substances (neurotransmitters) that diffuse across the synapse Slows neural transmission Amount of neurotransmitter (NT) release proportional to Ca++ influx
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Neurotransmitters Acetylcholine Catacholamines Serotonin Dopamine
Norepinephrine Epinephrine Serotonin Dopamine Glutamate Gamma-amino butyric acid (GABA) Certain amino acids Variety of peptides
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Neurons May release more than one substance upon stimulation
Neurotransmitter like norepinephrine Neuromodulator like neuropeptide Y (NPY)
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Postsynaptic Cell Response
Varies with the NT Excitatory NT causes a excitatory postsynaptic potential (EPSP) Increased membrane permeability to Na+ and/or Ca++ influx Inhibitory NT causes an inhibitory postsynaptic potential (IPSP) Increased membrane permeability to Cl- influx or K+ efflux Response of Postsynpatic Cell reflects integration of all input
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Response of Postsynaptic Cell
Stimulation causing an AP EPSP > IPSP > threshold Stimulation leading to facilitation EPSP > IPSP < threshold Inhibition EPSP < IPSP
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Somatic Sensory System
Nerve fiber types (Type I, II, III, IV) based on fiber diameter (Type I largest, Type IV smallest) Ia - Annulospiral (1o) endings of muscle spindles Ib - From golgi tendon organs II Flower spray (2o) endings of muscle spindles High disrimination touch ( Meissner’s) Pressure III Nociception, temperature, some touch (crude) IV- nociception and temperature (unmyelinated) crude touch and pressure
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Transduction Stimulus is changed into electrical signal
Different types of stimuli mechanical deformation chemical change in temperature electromagnetic
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Sensory systems All sensory systems mediate 4 attributes of a stimulus no matter what type of sensation modality location intensity timing
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Receptor Potential Membrane potential of the receptor
A change in the receptor potential is associated with opening of ion (Na+) channels Above threshold as the receptor potential becomes less negative the frequency of AP into the CNS increases
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Labeled Line Principle
Different modalities of sensation depend on the termination point in the CNS type of sensation felt when a nerve fiber is stimulated (e.g. pain, touch, sight, sound) is determined by termination point in CNS labeled line principle refers to the specificity of nerve fibers transmitting only one modality of sensation Capable of change, e.g. visual cortex in blind people active when they are reading Braille
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Adaptation Slow-provide continuous information (tonic)-relatively non adapting-respond to sustained stimulus joint capsul muscle spindle Merkel’s discs punctate receptive fields Ruffini end organ’s (corpusles) activated by stretching the skin
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Adaptation Rapid (Fast) or phasic
react strongly when a change is taking place respond to vibration hair receptors Hz Pacinian corpuscles 250 Hz Meissner’s corpuscles Hz (Hz represents optimum stimulus rate)
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Sensory innervation of Spinal joints
Tremendous amount of innervation with cervical joints the most heavily innervated Four types of sensory receptors Type I, II, III, IV
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Types of joint mechanoreceptors
Type I- outer layer of capsule- low threshold, slowly adapts, dynamic, tonic effects on LMN Type II- deeper layer of capsule- low threshold, monitors joint movement, rapidly adapts, phasic effects on LMN Type III- high threshold, slowly adapts, joint version of GTO Type IV- nociceptors, very high threshold, inactive in normal joint, active with swelling, narrowing of joint.
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Stereognosis The ability to perceive form through touch
tests the ability of dorsal column-medial lemniscal system to transmit sensations from the hand also tests ability of cognitive processes in the brain where integration occurs The ability to recognize objects placed in the hand on the basis of touch alone is one of the most important complex functions of the somatosensory system.
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Receptors in skin Most objects that we handle are larger than the receptive field of any receptor in the hand These objects stimulate a large population of sensory nerve fibers each of which scans a small portion of the object Deconstruction occurs at the periphery By analyzing which fibers have been stimulated the brain reconstructs the pattern
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Mechanoreceptors in the Skin
Rapidly adapting cutaneous Meissner’s corpuscles in glabrous (non hairy) skin- (more superficial) signals edges Hair follicle receptors in hairy skin Pacinian corpuscles in subcutaneous tissue (deeper)
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Mechanoreceptors in the Skin
Slowly adapting cutaneous Merkel’s discs have punctate receptive fields (superficial) senses curvature of an object’s surface Ruffini end organs activated by stretching the skin (deep) even at some distance away from receptor
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Mechanoreceptors in Glabrous (non hairy) Skin
Superficial Deep Small field Large field Rapid adaptation Meissner’s Corpuscle Pacinian Merkel’s Disc Ruffini End Organ Slow adaptation
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Somatic Sensory Cortex
Receives projections from the thalamus Somatotopic organization (homunculus) Each central neuron has a receptive field size of cortical representation varies in different areas of skin based on density of receptors lateral inhibition improves two point discrimination
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Somatosensory Cortex Two major pathways
Dorsal column-medial lemniscal system Most aspects of touch, proprioception Anterolateral system Sensations of pain (nociception) and temperature Sexual sensations, tickle and itch Crude touch and pressure Conduction velocity 1/3 – ½ that of dorsal columns
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Somatosensory Cortex (SSC)
Inputs to SSC are organized into columns by submodality cortical neurons defined by receptive field & modality most nerve cells are responsive to only one modality e.g. superficial tactile, deep pressure, temperature, nociception some columns activated by rapidly adapting Messiner’s, others by slowly adapting Merkel’s, still others by Paccinian corp.
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Somatosensory cortex Brodman area 3, 1, 2 (dominate input)
3a-from muscle stretch receptors (spindles) 3b-from cutaneous receptors 2-from deep pressure receptors 1-rapidly adapting cutaneous receptors These 4 areas are extensively interconnected (serial & parallel processing) Each of the 4 regions contains a complete map of the body surface “homonculus”
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Somatosensory Cortex 3 different types of neurons in BM area 1,2 have complex feature detection capabilities Motion sensitive neurons respond well to movement in all directions but not selectively to movement in any one direction Direction-sensitive neurons respond much better to movement in one direction than in another Orientation-sensitive neurons respond best to movement along a specific axis
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Other Somatosensory Cortical Areas
Posterior parietal cortex (BM 5 & 7) BM 5 integrates tactile information from mechanoreceptors in skin with proprioceptive inputs from underlying muscles & joints BM 7 receives visual, tactile, proprioceptive inputs intergrates stereognostic and visual information Projects to motor areas of frontal lobe sensory initiation & guidance of movement
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Secondary SSC (S-II) Secondary somatic sensory cortex (S-II)
located in superior bank of the lateral fissure projections from S-1 are required for function of S-II projects to the insular cortex, which innervates regions of temporal lobe believed to be important in tactile memory
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Pain vs. Nociception Nociception-reception of signals in CNS evoked by stimulation of specialized sensory receptors (nociceptors) that provide information about tissue damage from external or internal sources Activated by mechanical, thermal, chemical Pain-perception of adversive or unpleasant sensation that originates from a specific region of the body Sensations of pain Pricking, burning, aching stinging soreness
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Nociceptors Least differentiated of all sensory receptors
Can be sensitized by tissue damage hyperalgesia repeated heating axon reflex may cause spread of hyperalgesia in periphery sensitization of central nociceptor neurons as a result of sustained activation
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Sensitization of Nociceptors
Potassium from damaged cells-activation Serotonin from platelets- activation Bradykinin from plasma kininogen-activate Histamine from mast cells-activation Prostaglandins & leukotriens from arachidonic acid-damaged cells-sensitize Substance P from the 1o afferent-sensitize
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Nociceptive pathways Fast A delta fibers glutamate neospinothalamic
mechanical, thermal good localization sharp, pricking terminate in VB complex of thalamus Slow C fibers substance P paleospinothalamic polymodal/chemical poor localization dull, burning, aching terminate; RF tectal area of mesen. Periaqueductal gray
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Nociceptive pathways Spinothalamic-major Spinoreticular
neo- fast (A delta) paleo- slow (C fibers) Spinoreticular Spinomesencephalic Spinocervical (mostly tactile) Dorsal columns- (mostly tactile)
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Pain Control Mechanisms
Peripheral Gating theory involves inhibitory interneruon in cord impacting nocicep. projection neurons inhibited by C fibers stimulated by A alpha & beta fibers TENS Central Direct electrical + to brain -> analgesia Nociceptive control pathways descend to cord Endogenous opiods
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Muscle Receptors Muscle contain 2 types of sensory receptors
muscle spindles respond to stretch located within belly of muscle in parallel with extrafusal fibers (spindles are intrafusal fibers) innervated by 2 types of myelinated afferent fibers group Ia (large diameter) group II (small diameter) innervated by gamma motor neurons that regulate the sensitivity of the spindle golgi tendon organs respond to tension located at junction of muscle & tendon innervated by group Ib afferent fibers
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Muscle Spindles Nuclear chain Nuclear bag-
Most responsive to muscle shortening Nuclear bag- most responsive to muscle lengthening Dynamic vs static bag A typical mammalian muscle spindle contains one of each type of bag fiber & a variable number of chain fibers ( 5)
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Muscle Spindles sensory endings
primary-usually 1/spindle & include all branches of Ia afferent axon innervate all three types much more sensitive to rate of change of length than secondary endings secondary-usually 1/spindle from group II afferent innervate only on chain and static bag information about static length of muscle
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Gamma Motor System Innervates intrafusal fibers Controlled by:
Reticular formation Mesencephalic area appears to regulate rhythmic gate Vestibular system Lateral vestibulospinal tract facilitates gamma motor neuron antigravity control Cutaneous sensory receptors Over skeletal muscle, sensory afferent activating gamma motor neurons
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Golgi tendon organ (GTO)
Sensitive to changes in tension each tendon organ is innervated by single group Ib axon that branches & intertwines among braided collagen fascicles. Stretching tendon organ straightens collagen bundles which compresses & elongates nerve endings causing them to fire firing rate very sensitive to changes in tension greater response associated with contraction vs. stretch (collagen stiffer than muscle fiber)
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CNS control of spindle sensitivity
Gamma motor innervation to the spindle causes contraction of the ends of the spindle This allows the spindle to shorten & function while the muscle is contracting Spindle operate over wide range of muscle length This is due to simultaneously activating both alpha & gamma motor neurons during muscle contraction. (alpha-gamma coactivation) In slow voluntary movements Ia afferents often increase rate of discharge as muscle is shortening
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CNS control of spindle sensitivity
In movement the Ia afferent’s discharge rate is very sensitive to variartions in the rate of change of muscle length This information can be used by the nervous system to compensate for irregularities in the trajectory of a movement & to detect fatigue of local groups of muscle fibers
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Spindles and GTO’s As a muscle contracts against a load:
Spindle activity tends to decrease GTO activity tends to increase As a muscle is stretched Spindle activity increases GTO activity will initially decrease
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Summary Spindles in conjunction with GTO’s provide the CNS with continuous information about the mechanical state of a muscle For virtually all higher order perceptual processes, the brain must correlate sensory input with motor output to accurately assess the bodies interaction with its environment
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Transmission of signals
Spatial summation increasing signal strength transmitted by progressively greater # of fibers receptor field # of endings diminish as you move from center to periphery overlap between fibers Temporal summation increasing signal strength by frequency of IPS
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Neuronal Pools Input fibers Output fibers
divide hundreds to thousands of times to synapse with arborized dendrites stimulatory field Decreases as you move out from center Output fibers impacted by input fibers but not equally Excitation-supra-threshold stimulus Facilitation-sub-threshold stimulus Inhibition-release of inhibitory NT
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Neuronal Pools Divergence Convergence
in the same tract into multiple tracts Convergence from a single source from multiple sources Neuronal circuit causing both excitation and inhibition (e.g. reciprocal inhibition) insertion of inhibitory neuron
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Neuronal Pools Prolongation of Signals Synaptic Afterdischarge
postsynaptic potential lasts for msec can continue to excite neuron Reverberatory circuit positive feedback within circuit due to collateral fibers which restimulate itself or neighboring neuron in the same circuit subject to facilitation or inhibition
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Neuronal Pools Continuous signal output-self excitatory
continuous intrinsic neuronal discharge less negative membrane potential leakly membrane to Na+/Ca++ continuous reverberatory signals IPS increased with excitation IPS decreased with inhibition carrier wave type of information transmission excitation and inhibition are not the cause of the output, they modify output up or down ANS works in this fashion to control HR, vascular tone, gut motility, etc.
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Rhythmical Signal Output
Almost all result from reverberating circuits excitatory signals can increases amplitude & frequency of rhythmic output inhibitory signals can decrease amplitude & frequency of rhythmic output examples include the dorsal respiratory center in medulla and its effect on phrenic nerve activity to the diaphragm
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Stability of Neuronal Circuits
Almost every part of the brain connects with every other part directly or indirectly Problem of over-excitation (epileptic seizure) Problem controlled by: inhibitory circuits fatigue of synapses decreasing resting membrane potential long-term changes by down regulation of receptors
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Special Senses Vision Audition Chemical senses Taste Smell
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Refraction Light rays are bent
refractive index = ratio of light in a vacuum to the velocity in that substance velocity of light in vacuum=300,000 km/sec Light year 9.46 X km Refractive indices of various media air = 1 cornea = 1.38 aqueous humor = 1.33 lens = 1.4 vitrous humor = 1.34
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Refraction of light by the eye
Refractive power of 59 D (cornea & lens) Diopter = 1 meter/ focal length central point 17 mm in front of retina inverted image- brain makes the flip lens strength can vary from D Parasympathetic + increases lens strength Greater refractive power needed to read text
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Errors of Refraction Emmetropia- normal vision; ciliary muscle relaxed in distant vision Hyperopia-“farsighted”- focal pt behind retina globe short or lens weak ; convex lens to correct Myopia-“nearsighted”- focal pt in front of retina globe long or lens strong’; concave lens to correct Astigmatism- irregularly shaped cornea (more common) lens (less common)
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Visual Acuity Snellen eye chart 20/20 is normal
ratio of what that person can see compared to a person with normal vision 20/20 is normal 20/40 less visual acuity What the subject sees at 20 feet, the normal person could see at 40 feet. 20/10 better than normal visual acuity What the subject sees at 20 feet, the normal person could see at 10 feet
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Visual acuity The fovea centralis is the area of greatest visual acuity it is less than .5 mm in diameter (< 2 deg of visual field) outside fovea visual acuity decreases to more than 10 fold near periphery point sources of light two apart on retina can be distinguished as two separate points
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Fovea and acute visual acuity
Central fovea-area of greatest acuity composed almost entirely of long slender cones aids in detection of detail blood vessels, ganglionic cells, inner nuclear & plexiform layers are displaced laterally allows light to pass relatively unimpeded to receptors
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Depth Perception Relative size Moving parallax
the closer the object, the larger it appears learned from previous experience Moving parallax As the head moves, objects closer move across the visual field at a greater rate Stereopsis- binocular vision eyes separated by 2 inches- slight difference in position of visual image on both retinas, closer objects are more laterally placed
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Accomodation Increasing lens strength from 20 -34 D
Parasympathetic + causes contraction of ciliary muscle allowing relaxation of suspensory ligaments attached radially around lens, which becomes more convex, increasing refractive power Associated with close vision (e.g. reading) Presbyopia- loss of elasticity of lens w/ age decreases accomodation
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Formation of Aqueous Humor
Secreted by ciliary body (epithelium) 2-3 ul/min flows into anterior chamber and drained by Canal of Schlemm (vein) intraocular pressure mmHg. Glaucoma- increased intraocular P. compression of optic N.-can lead to blindness treatment; drugs & surgery
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Photoreceptors Rods & Cones
Light breaks down rhodopsin (rods) and cone pigments (cones) rhodopsin Na+ conductance photoreceptors hyperpolarize release less NT (glutamate) when stimulated by light
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Bipolar Cells Connect photoreceptors to either ganglionic cells or amacrine cells passive spread of summated postsynaptic potentials (No AP) Two types “ON”- hyperpolarized by NT glutamate “OFF”- depolarized by NT glutamate
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Ganglionic Cells Can be of the “ON” or “OFF” variety
“ON” bipolar + “ON” ganglionic “OFF” bipolar + “OFF” ganglionic Generate AP carried by optic nerve Three subtypes X (P) cells Y (M) cells W cells
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X vs Y Ganglionic cells Cell type X(P) Y(M) Input Bipolar Amacrine
Receptive field Small Large Conduction vel. Slow Fast Response Slow adaptation Fast adaptation Projects to Parvocellular of LGN Magnocellular of LGN Function color vision B&W movment
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W Ganglionic Cells smallest, slowest CV
many lack center-surround antagonistic fields they act as light intensity detectors some respond to large field motion they can be direction sensitive Broad receptive fields
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Horozontal Cells Non spiking inhibitory interneurons
Make complex synaptic connections with photorecetors & bipolar cells Hyperpolarized when light stimulates input photoreceptors When they depolarize they inhibit photoreceptors Center-surround antagonism
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Amacrine Cells Receive input from bipolar cells
Project to ganglionic cells Several types releasing different NT GABA, dopamine Transform sustained “ON” or “OFF” to transient depolarization & AP in ganglionic cells
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Center-Surround Fields
Receptive fields of bipolar & gang. C. two concentric regions Center field mediated by all photoreceptors synapsing directly onto the bipolar cell Surround field mediated by photoreceptors which gain access to bipolar cells via horozontal c. If center is “on”, surround is “off”
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Receptive field size In fovea- ratio can be as low as 1 cone to 1 bipolar cell to 1 ganglionic cell In peripheral retina- hundreds of rods can supply a single bipolar cell & many bipolar cells connected to 1 ganglionic cell
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Dark Adaptation In sustained darkness reform light sensitive pigments (Rhodopsin & Cone Pigments) of retinal sensitivity 10,000 fold cone adaptation-<100 fold Adapt first within 10 minutes rod adaptation->100 fold Adapts slower but longer than cones (50 minutes) dilation of pupil neural adaptation
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Cones 3 populations of cones with different pigments-each having a different peak absorption Blue sensitive (445 nm) Green sensitive (535 nm) Red sensitive (570 nm)
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Visual Pathway Optic N to Optic Chiasm Optic Chiasm to Optic Tract
Optic Tract to Lateral Geniculate Lateral Geniculate to 10 Visual Cortex geniculocalcarine radiation
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Additional Visual Pathways
From Optic Tracts to: Suprachiasmatic Nucleus biologic clock function Pretectal Nuclei reflex movement of eyes- focus on objects of importance Superior Colliculus rapid directional movement of both eyes
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Primary Visual Cortex Brodman area 17 (V1)-2x neuronal density
Simple Cells-responds to bar of light/dark above & below layer IV Complex Cells-motion dependent but same orientation sensitivity as simple cells Color blobs-rich in cytochrome oxidase in center of each occular dominace band starting point of cortical color processing Vertical Columns-input into layer IV Hypercolumn-functional unit, block through all cortical layers about 1mm2
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Visual Association Cortex
Visual analysis proceeds along many paths in parallel form color motion depth
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Control of Pupillary Diameter
Para + causes size of pupil (miosis) Symp + causes size of pupil (mydriasis) Pupillary light reflex optic nerve to pretectal nuclei to Edinger-Westphal to ciliary ganglion to pupillary sphincter to cause constriction (Para)
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Function of extraoccular muscles
Medial rectus of one eye works with the lateral rectus of the other eye as a yoked pair to produce lateral eye movements Medial rectus adducts the eye Lateral rectus abducts the eye
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Raising/lowering/torsioning
Elevate Depress Torsion Abducted Adducted Eye Eye Superior rectus Inferior oblique Inferior rectus Superior oblique
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Innervation of extraoccular muscles
Extraoccular muscles controlled by CN III, IV, and VI CN VI controls the lateral rectus only CN IV controls the superior oblique only CN III controls the rest
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Sound Units of Sound is the decibel (dB) I (measured sound)
Decibel = 1/10 log I (standard sound) Reference Pressure for standard sound .02 X dynes/cm2
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Sound Energy is proportional to the square of pressure
A 10 fold increase in sound energy = 1 bel One dB represents an actual increase in sound E of about 1.26 X Ears can barely detect a change of 1 dB
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Different Levels of Sound
20 dB- whisper 60 dB- normal conversation 100 dB- symphony 130 dB- threshold of discomfort 160 dB- threshold of pain
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Frequencies of Audible Sound
In a young adult 20-20,000 Hz (decreases with age) Greatest acuity Hz
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Tympanic Membrane & Ossicles
Impedance matching-between sound waves in air & sound vibrations generated in the cochlear fluid 50-75% perfect for sound freq Hz Ossicular system reduces amplitude by 1/4 increases pressure against oval window 22X increased force (1.3) decreased area from TM to oval window (17)
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Ossicular system (cont.)
Non functional ossicles or ossicles absent decrease in loudness about dB medium voice now sounds like a whisper attenuation of sound by contraction of Stapedius muscle-pulls stapes outward Tensor tympani-pull malleous inward
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Attenuation of sound CNS reflex causes contraction of stapedius and tensor tympani muscles activated by loud sound and also by speech latency of about msec creation of rigid ossicular system which reduces ossicular conduction most effective at frequencies of < 1000 Hz. Protects cochlea from very loud noises, masks low freq sounds in loud environment
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Cochlea System of 3 coiled tubes Scala vestibuli Scala media
Scala tympani
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Scala Vestibuli Seperated from the scala media by Reissner’s membrane
Associated with the oval window filled with perilymph (similar to CSF)
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Scala Media Separated from scala tympani by basilar membrane
Filled with endolymph secreted by stria vascularis which actively transports K+ Top of hair cells bathed by endolymph
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Endocochlear potential
Scala media filled with endolymph (K+) baths the tops of hair cells Scala tympani filled with perilymph (CSF) baths the bottoms of hair cells electrical potential of +80 mv exists between endolymph and perilymph due to active transport of K+ into endolymph sensitizes hair cells inside of hair cells (-70 mv vs -150 mv)
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Scala Tympani Associated with the round window Filled with perilymph
baths lower bodies of hair cells
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Function of Cochlea Change mechanical vibrations in fluid into action potentials in the VIII CN Sound vibrations created in the fluid cause movement of the basilar membrane Increased displacement increased neuronal firing resulting an increase in sound intensity some hair cells only activated at high intensity
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Place Principle Different sound frequencies displace different areas of the basilar membrane natural resonant frequency hair cells near oval window (base) short and thick respond best to higher frequencies (>4500Hz) hair cells near helicotrema (apex) long and slender respond best to lower frequencies (<200 Hz)
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Central Auditory Pathway
Organ of Corti to ventral & dorsal cochlear nuclei in upper medulla Cochlear N to superior olivary N (most fibers pass contralateral, some stay ipsilateral) Superior olivary N to N of lateral lemniscus to inferior colliculus via lateral lemniscus Inferior colliculus to medial geniculate N Medial geniculate to primary auditory cortex
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Primary Auditory Cortex
Located in superior gyrus of temporal lobe tonotopic organization high frequency sounds posterior low frequency sounds anterior
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Air vs. Bone conduction Air conduction pathway involves external ear canal, middle ear, and inner ear Bone conduction pathway involves direct stimulation of cochlea via vibration of the skull (cochlea is imbedded in temporal bone) reduced hearing may involve: ossicles (air conduction loss) cochlea or associated neural pathway (sensory neural loss)
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Sound Localization Horizontal direction from which sound originates from determined by two principal mechanisms Time lag between ears functions best at frequencies < 3000 Hz. Involves medial superior olivary nucleus neurons that are time lag specific Difference in intensities of sounds in both ears involves lateral superior olivary nucleus
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Exteroceptive chemosenses
Taste Works together with smell Categories (Primary tastes) sweet salt sour bitter (lowest threshold-protective mechanism) Olfaction (Smell) Primary odors ( )
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Taste receptors May have preference for stimuli
influenced by past history recent past adaptation long standing memory conditioning-association
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Primary sensations of taste
Sour taste- caused by acids (hydrogen ion concentration) Salty taste- caused by ionized salts (primarily the [Na+]) Sweet taste- most are organic chemicals (e.g. sugars, esters glycols, alcohols, aldehydes, ketones, amides, amino acids) & inorganic salts of Pb & Be Bitter- no one class of compounds but: long chain organic compounds with N alkaloids (quinine,strychnine,caffeine, nicotine)
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Taste Taste sensations are generated by:
complex transactions among chemical and receptors in taste buds subsequent activities occuring along the taste pathways There is much sensory processing, centrifugal control, convergence, & global integration among related systems contributing to gustatory experiences
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Taste Buds Taste neuroepithelium - taste buds in tongue, pharynx, & larynx. Aggregated in relation to 3 kinds of papillae fungiform-blunt pegs 1-5 buds /top foliate-submerged pegs in serous fluid with 1000’s of taste buds on side circumvallate-stout central stalks in serous filled moats with taste buds on sides in fluid 40-50 modified epithelial cells grouped in barrel shaped aggregate beneath a small pore which opens onto epithelial surface
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Innervation of Taste Buds
each taste nerve arborizes & innervates several buds (convergence in 1st order) receptor cells activate nerve endings which synapse to base of receptor cell Individual cells in each bud differentiate, function & degenerate on a weekly basis taste nerves: continually remodel synapses on newly generated receptor cells provides trophic influences essential for regeneration of receptors & buds
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Adaptation of taste Rapid-within minutes
taste buds account for about 1/2 of adaptation the rest of adaptation occurs higher in CNS
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CNS pathway-taste Anterior 2/3 of tongue Posterior 1/3 of tongue
lingual N. to chorda tympani to facial (VII CN) Posterior 1/3 of tongue IX CN (Petrosal ganglion) base of tongue and palate X CN All of the above terminate in nucleus tractus solitarius (NTS)
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CNS pathway (taste cont)
From the NTS to VPM of thalamus via central tegmental tract (ipsilateral) which is just behind the medial lemniscus. From the thalmus to lower tip of the post-central gyrus in parietal cortex & adajacent opercular insular area in sylvian fissure
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Olfactory Membrane Superior part of nostril Olfactory cells
bipolar nerve cells 100 million in olfactory epithelium 6-12 olfactory hairs/cell project in mucus react to odors and stimulate cells
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Cells in Olfactory Membrane
Olfactory cells- bipolar nerve cells which project hairs in mucus in nasal cavity stimulated by odorants connect to olfactory bulb via cribiform plate Cells which make up Bowman’s glands secrete mucus Sustentacular cells supporting cells
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Characteristics of Odorants
Volatile slightly water soluble- for mucus slightly lipid soluble for membrane of cilia Threshold for smells Very low
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Primary sensations of smell
Anywhere from 100 to 1000 based on different receptor proteins odor blindness has been described for at least 50 different substances may involve lack of a specific receptor protein
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Receptor Resting membrane potential when not activated = -55 mv
1 impulse/ 20 sec to 2-3 impulses/ sec When activated membrane pot. = -30 mv 20 impulses/ sec
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Glomerulus in Olfactory Bulb
several thousand/bulb Connections between olfactory cells and cells of the olfactory tract receive axons from olfactory cells (25,000) receive dendrites from: large mitral cells (25) smaller tufted cells (60)
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Cells in Olfactory bulb
Mitral Cells- (continually active) send axons into CNS via olfactory tract Tufted Cells- (continually active) Granule Cells inhibitory cell which can decrease neural traffic in olfactory tracts receive input from centrifugal nerve fibers
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CNS pathways Very old- medial olfactory area
feeds into hypothalamus & primitive areas of limbic system (from medial pathway) basic olfactory reflexes Less old- lateral olfactory area prepyriform & pyriform cortex -only sensory pathway to cortex that doesn’t relay via thalamus (from lateral pathway) learned control/adversion Newer- passes through the thalamus to orbitofrontal cortex (from lateral pathway) - conscious analysis of odor
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Medial and Lateral pathways
2nd order neurons form the olfactory tract & project to the following 1o olfactory paleocortical areas Anterior olfactory nucleus Modulates information processing in olfactory bulbs Amygdala and olfactory tubercle Important in emotional, endocrine, and visceral responses of odors Pyriform and periamygdaloid cortex Olfactory perception Rostral entorhinal cortex Olfactory memories
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Homeostasis Concept whereby body states are regulated toward a steady state Proposed by Walter Cannon in 1932 At the same time Cannon introduced negative feedback regulation an important part of this feedback regulation is mediated by the ANS through the hypothalamus
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Autonomic Nervous System
Controls visceral functions functions to maintain a dynamic internal environment, necessary for proper function of cells, tissues, organs, under a wide variety of conditions & demands
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Autonomic Nervous System
Visceral & largely involuntary motor system Three major divisions Sympathetic Fight & flight & fright emergency situations where there is a sudden in internal or external environment Parasympathetic Rest and Digest Enteric neuronal network in the walls of GI tract
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ANS Primarily an effector system Two neuron system Controls
smooth muscle heart muscle exocrine glands Two neuron system Preganglionic fiber cell body in CNS Postganglionic fiber cell body outside CNS
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Sympathetic Nervous System
Pre-ganglionic cells intermediolateral horn cells C8 to L2 or L3 release primarily acetylcholine also releases some neuropeptides (eg. LHRH) Post-ganglionic cells Paravertebral or Prevertebral ganglia most fibers release norepinephrine also can release neuropeptides (eg. NPY)
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Mass SNS discharge Increase in arterial pressure
decreased blood flow to inactive organs/tissues increase rate of cellular metabolism increased blood glucose metabolism increased glycolysis in liver & muscle increased muscle strength increased mental activity increased rate of blood coagulation
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Normal Sympathetic Tone
1/2 to 2 Impulses/Sec Creates enough constriction in blood vessels to limit flow Most SNS terminals release norepinephrine release of norepinephrine depends on functional terminals which depend on nerve growth factor
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Parasympathetic Nervous System
Preganglionic neurons located in several cranial nerve nuclei in brainstem Edinger-Westphal nucleus (III) superior salivatory nucleus (VII) inferior salivatory nucleus (IX) dorsal motor (X) (secretomotor) nucleus ambiguus (X) (visceromotor) intermediolateral regions of S2,3,4 release acetylcholine
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Parasympathetic Nervous System
Postganglionic cells cranial ganglia ciliary ganglion pterygopalatine submandibular ganglia otic ganglia other ganglia located near or in the walls of visceral organs in thoracic, abdominal, & pelvic cavities release acetylcholine
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Parasympathetic nervous system
The vagus nerves innervate the heart, lungs, bronchi, liver, pancreas, & all the GI tract from the esophagus to the splenic flexure of the colon The remainder of the colon & rectum, urinary bladder, reproductive organs are innervated by sacral preganglionic nerves via pelvic nerves to postganglionic neurons in pelvic ganglia
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Enteric Nervous System
Located in wall of GI tract (100 million neurons) Activity modulated by ANS
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Enteric Nervous system
Preganglionic Parasympathetic project to enteric ganglia of stomach, colon, rectum via vagus & pelvic splanchnic nerves increase motility and tone relax sphincters stimulate secretion
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Enteric Nervous System
Myenteric Plexus (Auerbach’s) between longitudenal & circular muscle layer controls gut motility can coordinate peristalsis in intestinal tract that has been removed from the body excitatory motor neurons release Ach & sub P inhibitory motor neurons release Dynorphin & vasoactive intestinal peptide
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Enteric Nervous System
Submucosal Plexus Regulates: ion & water transport across the intestinal epithelium glandular secretion communicates with myenteric plexus releases neuropeptides well organized neural networks
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Visceral afferent fibers
Accompany visceral motor fibers in autonomic nerves supply information that originates in sensory receptors in viscera never reach level of consciousness responsible for afferent limb of viscerovisceral and viscerosomatic reflexes important for homeostatic control and adjustment to external stimuli
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Visceral afferents Many of these neurons may release an excitatory neurotransmitter such as glutamate Contain many neuropeptides can include nociceptors “visceral pain” distension of hollow viscus
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Neuropeptides (visceral afferent)
Angiotension II Arginine-vasopressin bombesin calcitonin gene-related peptide cholecystokinin galamin substance P enkephalin somatostatin vasoactive intestinal peptide
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Autonomic Reflexes Cardiovascular GI autonomic reflexes baroreceptor
Bainbridge reflex GI autonomic reflexes smell of food elicits parasympathetic release of digestive juices from secretory cells of GI tract fecal matter in rectum elicits strong peristaltic contractions to empty the bowel
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Intracellular Effects
SNS-postganglionic fibers Norepinephrine binds to a alpha or beta receptor which effects a G protein Gs proteins + adenyl cyclase which raises cAMP which in turn + protein kinase activity which increases membrane permeability to Na+ & Ca++ Parasympathetic-postganglionic fibers Acetylcholine binds to a muscarinic receptor which also effects a G protein Gi proteins - adenyl cyclase and has the opposite effect of Gs
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Effects of Stimulation
Eye:S dilates pupils P- constricts pupil, contracts ciliary muscle & increases lens strength Glands:in general stimulated by P but S + will concentrate secretion by decreasing blood flow. Sweat glands are exclusively innervated by cholinergic S GI tract:S -, P + (mediated by enteric) Heart: S +, P - Bld vessels:S constriction, P largely absent
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Effects of Stimulation
Airway smooth muscle: S dilation P constriction Ducts: S dilation P constriction Immune System: S inhibits, P ??
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Fate of released NT Acetylcholine (P) rapidly hydrolysed by aetylcholinesterase Norepinephrine uptake by the nerve terminals degraded by MAO, COMT carried away by blood
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Precursors for NT Tyrosine is the precursor for Dopamine, Norepinephrine & Epinephrine Choline is the precursor for Acetylcholine
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Receptors Adrenergic Acetylcholine receptors Alpha Beta Nicotinic
found at synapes between pre & post ganglionic fibers (both S & P) Muscarinic found at effector organs
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Receptors Receptor populations are dynamic Up-regulate Down-regulate
increased # of receptors Increased sensitivity to neurotransmitter Down-regulate decreased # of receptors Decreased sensitivity to neurotransmitter Denervation supersensitivity Cut nerves and increased # of receptors causing increased sensitivity to the same amount of NT
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Higher control of ANS Many neuronal areas in the brain stem reticular substance and along the course of the tractus solitarius of the medulla, pons, & mesencephalon as well as in many special nuclei (hypothalamus) control different autonomic functions. ANS activated, regulated by centers in: spinal cord, brain stem, hypothalamus, higher centers (e.g. limbic system & cerebral cortex)
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Neural immunoregulation
Nerve fibers project into every organ involved in monitoring both internal & external environment controls output of endocrine & exocrine glands essential components of homeostatic mechanisms to maintain viability of organism local monitoring & modulation of host defense & CNS coordinates host defense activity
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Central Autonomic Regulation
Major relay cell groups in brain regulate afferent & efferent information convergence of autonomic information onto discrete brain nuclei autonomic function is modulated by ’s in preganglionic SNS or Para tone and/or ’s in neuroendocrine (NE) effectors
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Central Autonomic Regulation
different components of central autonomic regulation are reciprocally innervated parallel pathways carry autonomic info to other structures multiple chemical substances mediate transduction of neuronal infomation
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Important Central Autonomic Areas
Nucleus Tractus Solitarius Parabrachial Nucleus Locus Coeruleus Amygdala Cerebral Cortex Hypothalamus Circumventricular Organs (fenestrated caps)
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Control of Complex Movements
Involve Cerebral Cortex Basal Ganglia Cerebellum Thalamus Brain Stem Spinal Cord
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Motor Cortex Primary motor cortex Premotor area
somatotopic arrangement greater than 1/2 controls hands & speech + of neuron stimulate movements instead of contracting a single muscle Premotor area anterior to lateral portions of primary motor cortex below supplemental area projects to 10 motor cortex and basal ganglia
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Motor Cortex (cont.) Supplemental motor area
superior to premotor area lying mainly in the longitudnal fissure functions in concert with premotor area to provide: attitudinal movements fixation movements positional movements of head & eyes background for finer motor control of arms/hands
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The reticular nuclei Pontine reticular nuclei
transmit excitatory signals via the pontine (medial) reticulospinal tract stimulate the axial trunk & extensor muscles that support the body against gravity receive stimulation from vestibular nuclei & deep nuclei of the cerebellum high degree of natural excitability
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The Reticular Nuclei (cont.)
Medullary reticular nuclei transmit inhibitory signals to the same antigravity muscles via the medullary (lateral) reticulospinal tract receive strong input from the cortex, red nucleus, and other motor pathways counterbalance excitatory signals from the pontine reticular nuclei allows tone to be increased or decreased depending on function needing to be performed
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Role of brain stem in controlling motor function
Control of respiration Control of cardiovascular system Control of GI function Control of many stereotyped movements Control of equilibrium Control of eye movement
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Primary Motor Cortex Vertical Columnar Arrangement
functions as an integrative processing system pyramidal cells to achieve muscle contraction Pyramidal cells (two types of output signals) dynamic signal excessively excited at the onset of contraction to initiate muscle contraction static signal fire at slower rate to maintain contraction
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Initiation of voluntary movement
Plan and Program Begins in somatosensory association areas Execution Motor cortex outputs To the cord -> skeletal muscle To the spinocerebellum Feedback from the periphery
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Postural Reflexes Impossible to separate postural adjustments from voluntary movement maintain body in up-right balanced position provide constant adjustments necessary to maintain stable postural background for voluntary movement adjustments include static reflexes (sustained contraction) & dynamic short term phasic reflexes (transient movements)
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Postural Control (cont)
A major factor is variation of in threshold of spinal stretch reflexes caused by changes in excitability of motor neurons & changes in rate of discharge in the gamma efferent neurons to muscle spindles
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Postural Reflexes Three types of postural reflexes vestibular reflexes
tonic neck reflexes righting reflexes
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Vestibular function Vestibular apparatus-organ that detects sensations of equilibrium Consists of semicircular canals & utricle & saccule embedded in the petrous portion of temporal bone provides information about position and movement of head in space helps maintain body balance and helps coordinate movements
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Vestibular apparatus Utricle and Saccule Macula is the sensory area
covered with a gelatinous layer in which many small calcium carbonate crystals are imbedded hair cells in macula project cilia into gelatinous layer directional sensitivity of hair cells to cause depolarization or hyperpolarization detect orientation of head w/ respect to gravity detect linear acceleration
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Vestibular apparatus (cont)
Semicircular canals Crista ampularis in swelling (ampulla) Cupula loose gelatinous tissue mass on top of crista stimulated as head begins to rotate 3 pairs of canals bilaterally at 90o to one another. (anterior, horizontal, posterior) Each set lie in the same plane right anterior - left posterior right and left horizontal left anterior - right posterior
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Semicircular Canals Filled with endolymph
As head begins to rotate, fluid lags behind and bend cupula generates a receptor potential which alters the firing rate in VIII CN which projects to the vestibular nuclei detects rotational acceleration & deceleration
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Semicircular Canals Stimulation of semicircular canals on side rotation is into. (e.g. Right or clockwise rotation will stimulate right canal) Stimulation of semicircular canals is associated with increased extensor tone Stimulation of semicircular canals is associated with nystagmus
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Semicircular Canals Connections with vestibular nucleus via CN VIII
Vestibular nuclei makes connections with CN associated with occular movements (III,IV, VI) and cerebellum Can stimulate nystagmus slow component-(tracking)can be initiated by semicircular canals fast component- (jump ahead to new focal spot) initiated by brain stem nuclei
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Semicircular Canals Thought to have a predictive function to prevent malequilibrium Anticipitory corrections works in close concert with cerebellum especially the flocculonodular lobe
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Other Factors - Equilibrium
Neck proprioceptors-provides information about the orientation of the head with the rest of the body projects to vestibular apparatus & cerebellum cervical joints proprioceptors can override signals from the vestibular apparatus & prevent a feeling of malequilibrium Proprioceptive and Exteroceptive information from other parts of the body Visual signals
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Posture Represents overall position of the body & limbs relative to one another & their orientation in space Postural adjustments are necessary for all motor tasks & need to be integrated with voluntary movement
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Vestibular & Neck Reflexes
Have opposing actions on limb muscles Most pronounced when the spinal circuits are released from cortical inhibition Vestibular reflexes evoked by changes in position of the head Neck reflexes are triggered by tilting or turning the neck
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Postural Adjustments Functions Major mechanisms
support head & body against gravity maintain center of the body’s mass aligned & balanced over base of support on the ground stabilize supporting parts of the body while others are being moved Major mechanisms anticipatory (feed forward)-predict disturbances modified by experience; improves with practice compensatory (feedback) evoked by sensory events following loss of balance
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Postural adjustments Induced by body sway
Extremely rapid (like simple stretch reflex) Relatively stereotyped spatiotemporal organization (like ssr) appropriately scaled to achieve goal of stable posture (unlike ssr) refined continuously by practice (like skilled voluntary movements)
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Postural mechanisms Sensory input from:
cutaneous receptors from the skin (esp feet) proprioceptors from joints & muscles short latency ( ms) vestibular signals (head motion) longer latency (2x proprioceptor latency) visual signals
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Postural Mechanisms (cont)
In sway, contraction of muscles to maintain balance occur in distal to proximal sequence forward sway Gastro>ham>para backward sway Tib>quad>abd responses that stabilize posture are facilitated responses that destabilize posture inhibited
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Effect of tonic neck reflexes on limb muscles
Extension of neck + extensors of arms/legs Flexion of neck + flexors of arms/legs Rotation or lateral bending + extensors ipsilateral + flexors contralateral
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Basal Ganglia Input nuclei Output nuclei Caudate Putamen
caudate + putamen = striatum Nucleus accumbens Output nuclei Globus Pallidus-external segment Subthalamic nucleus Substantia nigra Ventral tegmental area
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Basal Ganglia Consist of 4 principal nuclei
the striatum (caudate & putamen) the globus pallidus (internal & external) the substantia nigra subthalamic nucleus
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Basal Ganglia Do not have direct input or output connections with the spinal cord Motor functions of the basal ganglia are mediated by the motor areas of the cortex Disorders have three characteristic types of motor disturbances tremor & other involuntary movements changes in posture & muscle tone poverty & slowness of movement
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Two major circuits of BG
Caudate circuit large input into caudate from the association areas of the brain caudate nucleus plays a major role in cognitive control of motor activity cognitive control of motor activity Putamen circuit subconcious execution of learned patterns of movement
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Cerebellum-”little brain”
By weight 10% of total brain Contains > 1/2 of all neurons in brain Highly regular structure motor systems are mapped here Complete destruction produces no sensory impairment & no loss in muscle strength Plays a crucial indirect role in movement & posture by adjusting the output of the major descending motor systems
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Functional Divisions Vestibulocerebellum (floculonodular lobe)
input-vestibular N: output-vestibular N. fxn-governs eye movement & body equilibrium Spinocerebellum (vermis &intermediate) input-periphery & spinal cord: output-cortex fxn-major role in movement, influencing medial & lateral descending motor systems Cerebrocerebellum (lateral zone) input-pontine N. output-pre & motor cortex fxn-planning & initiation of movement & extramotor prediction mental rehersal of complex motor actions conscious assessment of movement errors Higher cognitive function-executive functions
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Cerebellum Cerebellar cortex
three pairs of deep nuclei from which most of output originates from. fastigial Interposed (globose & emboliform) dentate connected to brain stem by 3 sets of peduncles superior which contains most efferent project. Middle Inferior- most afferent from spinal cord
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Major features of cerebellum fxn
receives info about plans for movement from brain structures concerned with programming & execution of movement cerebellum receives information about motor performance from peripheral feedback during course of movement compares central info w/ actual motor response projects to descending motor systems via cortex
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Higher Cortical function
Cerebral Cortex About 100 billion neurons contained in a thin layer 2-5 mm thick covering all convolutions of the cerebrum Three major cell types Granular, pyramidal, fusiform Typically 6 layers (superficial to deep) molecular, external granular, external pyramidal, internal granular, internal pyramidal, mutiform All areas of cerebral cortex make extensive afferent & efferent connections with the thalamus
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The Cerebral Cortex Layer I -Molecular Layer
mostly axons Layer II-External Granule Layer granule (stellate) cells Layer III-External Pyramidal layer primary pyramidal cells
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Cerebral Cortex Layer IV-Internal Granule Layer
main granular cell layer Layer V- internal pyramidal layer dominated by giant pyramidal cells Layer VI- multiform layer all types of cells-pyramidal, stellate, fusiform
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Cerebral Cortex Three major cell types Pyramidal cells Granule cells
souce of corticospinal projections major efferent cell Granule cells short axons- function as interneurons (intra cortical processing) excitatory neurons release 1o glutamate inhibitory neurons release 1o GABA Fusiform cells least numerous of the three gives rise to output fibers from cortex
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Cerebral Cortex Most output leave cortex via V &VI
spinal cord tracts originate from layer V thalamic connections from layer V Most incoming sensory signals terminate in layer IV Most intracortical association functions - layers I, II, III large # of neurons in II, III- short horozontal connections with adjacent cortical areas
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Cerebral Cortex All areas of the cerebral cortex have extensive afferent and efferent connections with deeper structures of brain. (eg. Basal ganglia, thalamus etc.) Thalamic connections (afferent and efferent) are extremely important and extensive Cortical neurons (esp. in association areas) can change their function as functional demand changes
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Concept of a Dominant Hemisphere
General interpretative functions of Wernicke’s & angular gyrus as well as speech & motor control are more well developed in one cerebral hemisphere 95% of population- left hemisphere If dominate hemisphere sustains damage early in life, non dominate hemisphere can develop those capabilities of speech & language comprehension (Plasticity)
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Lingustic Dominance & Handedness
Dominant Hemisphere Left or mixed handed Left- 70% Right- 15% Both- 15% Right handed Left- 96% Right- 4% Both- 0%
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Right brain, left brain The two hemispheres are specialized for different functions dominant (usually left) language based intellectual functions interpretative functions of symbolism, understanding spoken, written words analytical functions- math speech non dominant (usually right) music non verbal visual experiences (e.g. body language) spatial relations
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Allocortex Made up of archicortex & paleocortex
10% of human cerebral cortex Includes the hippocampal formation which is folded into temporal lobe & only viewed after dissection hippocampus dentate gyrus subiculum
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Hippocampal formation
Three parts Hippocampus- 3 layers (I, V, VI) Dentate gyrus- 3 layers (I, IV, VI) Subiculum Receives 10 input from the entorhinal cortex of the parahippocampal gyrus through: perforant & alveolar pathway
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Hippocampal formation
Plays an important role in declarative memory Declarative- making declarative statements of memory Episodic-daily episodes of life Semantic-factual information
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Memory Memories are caused by groups of neurons that fire together in the same pattern each time they are activated. The links between individual neurons, which bind them into a single memory, are formed through a process called long-term potentiation. (LTP)
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Classification of Memory (cont)
Memory can also be classified as: Declarative-memory of details of an integrated thought memory of: surroundings, time relationships cause & meaning of the experience Reflexive (Skill)- associated with motor activities e.g. hitting a tennis ball which include complicated motor performance
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Role of Hippocampus in Memory
The hippocampus may store long term memory for weeks & gradually transfer it to specific regions of cerebral cortex The hippocampus has 3 major synaptic pathways each capable of long-term potentiation which is thought to play a role in the storage process
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Storage of Memory Long term memory is represented in mutiple regions throughout the nervous system Is associated with structural changes in synapes increase in # of both transmitter vesicles & release sites for neurotransmitter increase in # of presynaptic terminals changes in structures of dendritic spines increased number of synaptic connections
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Memory (cont) The memory capability that is spared following bilateral lesions of temporal lobe typically involves learned tasks that have two things in common tasks tend to be reflexive, not reflective & involve habits, motor, or perceptual skills do not require conscious awareness or complex cognitive processes. (e.g. comparison & evaluation
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Memory Environment alters human behavior by learning & memory Learning
process by which we acquire knowledge about the world Memory process by which knowledge is encoded, stored & retrieved
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Neural Basis of Memory Memory has stages & continually changing
long term memory- plastic changes physical changes coding memory are localized in multiple regions of the brain reflexive & declarative memory may involve different neuronal circuits
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Higher Cortical Function
Primary areas Visual- occipital pole (BM 17) Auditory-superior gyrus of temporal lobe (BM 41) Primary motor cortex-pre central gyrus (BM 4) Primary somatosensory cortex- post central gyrus (BM 3,1,2) Secondary and Association areas Large percentage of human brain
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Association Areas Integrate or associate info. from diverse sources
Large % of human cortex High level in the hierarchy Lesions here have subtle and unpredictable quality
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Association Areas Prefrontal Parieto-occipito-temporal Limbic
Executive functions Judgment Planning for the future holding & organizing events from memory for prospective action Processing emotion-learning to control emotion (acting unselfishly) Parieto-occipito-temporal Spatial relationships Recognizing complex form prosopagnosia Limbic Motivation, behavioral drives, emotion
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Heart muscle Atrial & Ventricular
striated enlongated grouped in irregular anatamosing columns 1-2 centrally located nuclei Specialized excitatory & conductive muscle fibers (SA node, AV node, Purkinje fibers) contract weakly few fibrils
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Syncytial nature of cardiac muscle
Syncytium = many acting as one Due to presence of intercalated discs low resistance pathways connecting cardiac cells end to end presence of gap junctions
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SA node Normal pacemaker of the heart Self excitatory nature
less negative Er leaky membrane to Na+/CA++ only slow Ca++/Na+ channels operational spontaneously depolarizes at fastest rate overdrive suppression-inhibits other cells automaticity contracts feebly Stretch on the SA node will increase Ca++ and/or Na+ permeability which will increase heart rate
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AV node Delays the wave of depolarization from entering the ventricle
allows the atria to contract slightly ahead of the ventricles (.1 sec delay) Slow conduction velocity due to smaller diameter fibers In absence of SA node, AV node may act as pacemaker but at a slower rate
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Cardiac Cycle Systole Diastole isovolumic contraction ejection
isovolumic relaxation rapid inflow % diastasis atrial systole %
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Cardiac cycle: Pressure changes Over time Left ventricular Volume changes EKG
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Ventricular Volumes End Diastolic Volume-(EDV)
volume in ventricles at the end of filling End Systolic Volume- (ESV) volume in ventricles at the end of ejection Stroke volume (EDV-ESV) volume ejected by ventricles Ejection fraction % of EDV ejected (SV/EDV X 100%) normal 50-60%
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Terms Preload-stretch on the wall prior to contraction (proportional to the EDV) Afterload-the changing resistance (impedance) that the heart has to pump against as blood is ejected. i.e. Changing aortic BP during ejection of blood from the left ventricle
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Atrial Pressure Waves A wave C wave V wave
associated with atrial contraction C wave associated with ventricular contraction bulging of AV valves and tugging on atrial muscle V wave associated with atrial filling
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Function of Valves Open with a forward pressure gradient
e.g. when LV pressure > the aortic pressure the aortic valve is open Close with a backward pressure gradient e.g. when aortic pressure > LV pressure the aortic valve is closed
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Heart Valves AV valves Semilunar valves Mitral & Tricupid
Thin & filmy Chorda tendineae act as check lines to prevent prolapse papillary muscles-increase tension on chorda t. Semilunar valves Aortic & Pulmonic stronger construction
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Law of Laplace Wall tension = (pressure)(radius)/2
At a given operating pressure as ventricular radius , developed wall tension . tension force of ventricular contraction two ventricles operating at the same pressure but with different chamber radii the larger chamber will have to generate more wall tension, consuming more energy & oxygen This law explains how capillaries can withstand high intravascular pressure because of a small radius, minimizes developed wall tension
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Control of Heart Pumping
Intrinsic properties of cardiac muscle cells Frank-Starling Law of the Heart Within physiologic limits the heart will pump all the blood that returns to it without allowing excessive damming of blood in veins heterometric & homeometric autoregulation direct stretch on the SA node
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Mechanism of Frank-Starling
Increased venous return causes increased stretch of cardiac muscle fibers. (Intrinsic effects) increased cross-bridge formation increased calcium influx both increases force of contraction increased stretch on SA node increases heart rate
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Heterometric autoregulation
Within limits as cardiac fibers are stretched the force of contraction is increased more cross bridge formation as actin overlap is removed more Ca++ influx into cell associated with the increased stretch
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Homeometric autoregulation
Ability to increase strength of contraction independent of a length change Flow induced Pressure induced Rate induced
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Extrinsic Influences on heart
Autonomic nervous system Hormonal influences Ionic influences Temperature influences
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Control of Heart by ANS Sympathetic innervation-
+ heart rate + strength of contraction + conduction velocity Parasympathetic innervation - heart rate - strength of contraction - conduction velocity
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Interaction of ANS SNS effects and Parasympathetic effects blocked using propranolol (beta blocker) & atropine (muscarinic blocker) respectively. HR will increase Strength of contraction decreases From the previous results it can be concluded that under resting conditions: Parasympathetic NS exerts a dominate inhibitory influence on heart rate Sympathetic NS exerts a dominate stimulatory influence on strength of contraction
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Cardioacclerator reflex
Stretch on right atrial wall + stretch receptors which in turn send signals to medulla oblongata + SNS outflow to heart AKA Bainbridge reflex Helps prevents damning of blood in the heart & central veins
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Major Hormonal Influences
Thyroid hormones + inotropic + chronotropic also causes an increase in CO by BMR
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Ionic influences Effect of elevated [K+]ECF
dilation and flaccidity of cardiac muscle at concentrations 2-3 X normal (8-12 meq/l) decreases resting membrane potential Effect of elevated [Ca++] ECF spastic contraction
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Effect of body temperature
Elevated body temperature HR increases about 10 beats for every degree F elevation in body temperature Contractile strength will increase temporarily but prolonged fever can decrease contractile strength due to exhaustion of metabolic systems Decreased body temperature decreased HR and strength
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Terminology Chronotropic (+ increases) (- decreases) Dromotropic
Anything that affects heart rate Dromotropic Anything that affects conduction velocity Inotropic Anything that affects strength of contraction eg. Caffeine would be a + chronotropic agent (increases heart rate)
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EKG Measures potential difference across the surface of the myocardium with respect to time lead-pair of electrodes axis of lead-line connecting leads transition line-line perpendicular to axis of lead
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Rate Paper speed- 25 mm/sec 1 mm = .04 sec.
Normal rate ranges usually between bps Greater than 100 = tachycardia Less than 50 = bradycardia
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Electrocardiography P wave-atrial depolarization
QRS complex-ventricular depolarization T wave-ventricular repolarization
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Leads A pair of recording electrodes
+ electrode is active - electrode is reference The direction of the deflection (+ or -) is based on what the active electrode sees relative to the reference electrode Routine EKG consists of 12 leads 6 frontal plane leads 6 chest leads (horizontal)
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Type of Deflection
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Hypertrophy Hypertrophy of one ventricle relative to the other can be associated with anything that creates an abnormally high work load on that chamber. e.g. Systemic hypertension increasing work load on the left ventricle prolonged QRS complex (> .12 sec) axis deviation to the side of problem increased voltage of QRS in V leads
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Blood flow to myocardium
The myocardium is supplied by the coronary arteries & their branches. Cells near the endocardium may be able to receive some O2 from chamber blood The heart muscle at a resting heart rate takes the maximum oxygen out of the perfusing coronary flow (70% extraction) Any demand must be met by coronary flow
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Circulation The main function of the systemic circulation is to deliver adequate oxygen, nutrients to the systemic tissues and remove carbon dioxide & other waste products from the systemic tissues The systemic circulation is also serves as a conduit for transport of hormones, and other substances and allows these substances to potentially act at a distant site from their production
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Functional Parts systemic arteries
designed to carry blood under high pressure out to the tissue beds arterioles & pre capillary sphincters act as control valves to regulate local flow capillaries- one cell layer thick exchange between tissue (cells) & blood venules collect blood from capillaries systemic veins return blood to heart
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Basic theory of circulatory function
Blood flow is proportional to metabolic demand Cardiac output controlled by local tissue flow Arterial pressure control is independent of local flow or cardiac output
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Hemodynamics Flow Pressure gradient Resistance Ohm’s Law
V = IR (Analogous to P = QR)
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Flow (Q) The volume of blood that passes a certain point per unit time (eg. ml/min) Q = velocity X cross sectional area At a given flow, the velocity is inversely proportional to the total cross sectional area Q = P / R Flow is directly proportional to P and inversely proportional to resistance (R)
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Pressure gradient Driving force of blood
difference in pressure between two points proportional to flow (Q) At a given Q the greater the drop in P in a segment or compartment the greater the resistance to flow.
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Resistance R= 8l/ r4 Parallel circuit Series circuit
= viscosity, l = length of vessel, r = radius Parallel circuit 1/RT= 1/R1+ 1/R2 + 1/R3 + … 1/RN RT < smallest individual R Series circuit RT = R1 + R2 + R3 + … RN RT = sum of individual R’s The systemic circulation is predominantly a parallel circuit
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Advantages of Parallel Circuitry
Independence of local flow control increase/decrease flow to tissues independently Minimizes total peripheral resistance (TPR) Oxygen rich blood supply to every tissue
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Viscosity Internal friction of a fluid associated with the intermolecular attraction Blood is a suspension with a viscosity of 3 most of viscosity due to RBC’s Plasma has a viscosity of 1.5 Water is the standard with a viscosity of 1 With blood, viscosity 1/ velocity
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Viscosity considerations at microcirculation
velocity decreases which increases viscosity due to elements in blood sticking together cells can get stuck at constriction points momentarily which increases apparent viscosity fibrinogen increases flexibility of RBC’s in small vessels cells line up which decreases viscosity and offsets the above to some degree (Fahaeus-Lindquist)
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Hematocrit % of packed cell volume (10 RBC’s) Normal range 38%-45%
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Laminar vs. Turbulent Flow
Streamline silent most efficient normal Cross mixing vibrational noise least efficient frequently associated with vessel disease (bruit)
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Reynold’s number Probability statement for turbulent flow
The greater the R#, the greater the probability for turbulence R# = v D / v = velocity, D = tube diameter, = density, = viscosity If R# < 2000 flow is usually laminar If R# > 3000 flow is usually turbulent
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Doppler Ultrasonic Flow-meter
Ultrasound to determine velocity of flow Doppler frequency shift function of the velocity of flow RBC’s moving toward transmitter, compress sound waves, frequency of returning waves Broad vs. narrow frequency bands Broad band is associated with turbulent flow narrow band is associated laminar flow
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Distensibility Vs. Compliance
Distensibility is the ability of a vessel to stretch (distend) Compliance is the ability of a vessel to stretch and hold volume
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Distensibility Vs. Compliance
Distensibility = Vol/ Pressure X Ini. Vol Compliance = Vol/ Pressure Compliance = Distensibility X Initial Vol.
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Volume-Pressure relationships
A volume pressure In systemic arteries a small volume is associated with a large pressure In systemic veins a large volume is associated with a small pressure Veins are about 8 X more distensible and 24 X more compliant than systemic arteries Wall tone 1/ compliance & distensibility
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Control of Blood Flow (Q)
Local blood flow is regulated in proportion to the metabolic demand in most tissues Short term control involves vasodilatation vasoconstriction of precapillary resist. vessels arterioles, metarterioles, pre-capillary sphincters Long term control involves changes in tissue vascularity formation or dissolution of vessels vascular endothelial growth factor & angiogenin
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Role of arterioles Arterioles act as an intergrator of multiple inputs
Arterioles are richly innervated by SNS vasoconstrictor fibers and have alpha receptors Arterioles are also effected by local factors (e.g.)vasodilators, circulating substances
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Local Control of Flow (short term)
Involves vasoconstriction/vasodilatation of precapillary resistance vessels Local vasodilator theory Active tissue release local vasodilator (metabolites) which relax vascular smooth muscle Oxygen demand theory (older theory) As tissue uses up oxygen, vascular smooth muscle cannot maintain constriction
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Local Vasodilators Adenosine carbon dioxide
adenosine phosphate compounds histamine potassium ions hydrogen ions PGE & PGI series prostaglandins
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Autoregulation The ability to keep blood flow (Q) constant in the face of a changing arterial BP Most tissues show some degree of autoregulation Q metabolic demand In the kidney both renal Q and glomerular filtration rate (GFR) are autoregulated
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Control of Flow (long term)
Changes in tissue vascularity On going day to day reconstruction of the vascular system Angiogenesis-production of new microvessels arteriogenesis shear stress caused by enhanced blood flow velocity associated with partial occlusion Angiogenic factors small peptides-stimulate growth of new vessels VEGF (vascular endothelial growth factor)
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Changes in tissue vascularity
Stress activated endothelium up-regulates expression of monocyte chemoattractant protein-1 (MCP-1) attraction of monocytes that invade arterioles other adhesion molecules & growth factors participate with MCP-1 in an inflammatory reaction and cell death in potential collateral vessels followed by remodeling & development of new & enlarged collateral arteries & arterioles
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Changes in tissue vacularity (cont.)
Hypoxia causes release of VEGF enhanced production of VEGF partly mediated by adenosine in response to hypoxia VEGF stimulates capillary proliferation and may also be involved in development of collateral arterial vessels NPY from SNS is angiogenic hyperactive SNS may compromise collateral blood flow by vasoconstriction
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Vasoactive Role of Endothelium
Release prostacyclin (PGI2) inhibits platelet aggregation relaxes vascular smooth muscle Releases nitric oxide (NO) which relaxes vascular smooth muscle NO release stimulated by: shear stress associated with increased flow acetylcholine binding to endothelium Releases endothelin & endothelial derived contracting factor constricts vascular smooth muscle
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Microcirculation Capillary is the functional unit of the circulation
bulk of exchange takes place here Vasomotion-intermittent contraction of metarterioles and precapillary sphincters functional Vs. non functional flow Mechanisms of exchange diffusion ultrafiltration vesicular transport
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Oxygen uptake/utilization
= the product of flow (Q) times the arterial-venous oxygen difference O uptake = (Q) (A-V O2 difference) Q=300 ml/min AO2= .2 ml O2/ml VO2= .15 ml O2/min 15 ml O2 = (300 ml/min) (.05 mlO2/ml) Functional or Nutritive flow (Q) is associated with increased oxygen uptake/utilization
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Capillary Exchange Passive Diffusion Ultrafiltration
permeability concentration gradient Ultrafiltration Bulk flow through a filter (capillary wall) Starling Forces Hydrostatic P Colloid Osmotic P Vesicular Transport larger MW non lipid soluble substances
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Ultrafiltration Hydrostatic P gradient (high to low)
Capillary HP averages 17 mmHg Interstitial HP averages -3 mmHg Colloid Osmotic P (low to high) Capillary COP averages 28 mmHg Interstitial COP averages 9 mmHg Net Filtration P = (CHP-IHP)-(CCOP-ICOP) =
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Colloid Osmotic Considerations
The colloid osmotic pressure is a function of the protein concentration Plasma Proteins Albumin (75%) Globulins (25%) Fibrinogen (<1%) Calculated Colloid Effect is 19 mmHg Actual Colloid Effect is 28 mmHg Discrepancy is due to the Donnan Effect
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Donnan Effect Increases the colloid osmotic effect
Large MW plasma proteins (1o albumen) carries negative charges which attract + ions (1o Na+) increasing the osmotic effect by about 50%
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Effect of Ultrastructure of Capillary Wall on Colloid Osmotic Pressure
Capillary wall can range from tight junctions (e.g. blood brain barrier) to discontinuous (e.g. liver capillaries) Glomerular Capillaries in kidney have filtration slits (fenestrations) Only that protein that cannot cross capillary wall can exert osmotic pressure
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Reflection Coefficient
Reflection Coefficient expresses how readily protein can cross capillary wall ranges between 0 and 1 If RC = 0 All colloid proteins freely cross wall, none are reflected, no colloid effect If RC = 1 All colloid proteins are reflected, none cross capillary wall, full colloid effect
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Lymphatic system Lymph capillaries drain excess fluid from interstitial spaces No true lymphatic vessels found in superficial portions of skin, CNS, endomysium of muscle, & bones Thoracic duct drains lower body & left side of head, left arm, part of chest Right lymph duct drains right side of head, neck, right arm and part of chest
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CNS-modified lymphatic function
No true lymphatic vessels in CNS Perivascular spaces contain CSF & communicate with subarachnoid space Plasma filtrate & escaped substances in perivascular spaces returned to the vascular system in the CSF via the arachnoid villi which empties into dural venous sinsus Acts a functional lymphatic system in CNS
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Formation of Lymph Excess plasma filtrate-resembles ISF from tissue it drains [Protein] 3-5 gm/dl in thoracic duct liver 6 gm/dl intestines 3-4 gm/dl most tissues ISF 2 gm/dl 2/3 of all lymph from liver & intestines Any factor that filtration and/or reabsorption will lymph formation
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Rate of Lymph Formation/Flow
Thoracic duct- 100 ml/hr. Right lymph duct- 20 ml/hr. Total lymph flow- 120 ml/hr (2.9 L/day) Every day a volume of lymph roughly equal to your entire plasma volume is filtered
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Function of Lymphatics
Return lost protein to the vascular system Drain excess plasma filtrate from ISF space Carry absorbed substances/nutrients (e.g. fat-chlyomicrons) from GI tract Filter lymph (defense function) at lymph nodes lymph nodes-meshwork of sinuses lined with tissue macrophages (phagocytosis)
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Arterial blood pressure
Arterial blood pressure is created by the interaction of blood with vascular wall Art BP = volume of blood interacting with the wall inflow (CO) - outflow (TPR) Art BP = CO X TPR Greater than 1/2 of TPR is at the level of systemic arterioles
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Systole During systole the left ventricular output (SV) is greater than peripheral runoff Therefore total blood volume rises which causes arterial BP to increase to a peak (systolic BP) The arteries are distended during this time
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Diastole While the left ventricle is filling, the arteries now are recoiling, which serves to maintain perfusion to the tissue beds Total blood volume in the arterial tree is decreasing which causes arterial BP to fall to a minimum value (diastolic BP)
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Hydralic Filtering Stretch (systole) & recoil (diastole) of the arterial tree that normally occurs during the cardiac cycle This phenomenon converts an intermittent output by the heart to a steady delivery at the tissue beds & saves the heart work As the distensibility of the arterial tree with age, hydralic filtering is reduced, and work load on the heart is increased
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Mean Arterial Blood Pressure
The mean arterial pressure (MAP) is not the arithmetical mean between systole & diastole determined by calculating the area under the curve, and dividing it into equal areas MAP= 1/3 Pulse Pressure + DBP (approximation)
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Effects of SNS + Most post-ganglionic SNS terminals release norepinephrine. The predominant receptor type is alpha () response is constriction of smooth muscle Constriction of arterioles reduce blood flow and help raise arterial blood pressure (BP) Constriction of arteries raise arterial BP Constriction of veins increases venous return
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SNS (cont) SNS + causes widespread vasoconstrictor causing blood flow with 3 exceptions Brain arterioles weakly innervated Lungs Pulmonary BF = C.O. Heart direct vasoconstrictor effects over-ridden by SNS induced increase in cardiac activity which causes release of local vasodilators (adenosine)
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Critical Closing Pressure
As arterial pressure falls, there is a critical pressure below which flow ceases due to the closure of the arterioles. This critical luminal pressure is required to keep arterioles from closing completely vascular tone is proportional to CCP e.g. SNS + of arterioles CCP
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Mean Circulatory Filling Pressure
If cardiac output is stopped, arterial pressure will fall and venous pressure will rise MCFP = equilibration pressure where arterial BP = venous BP equilibration pressure may be prevented by closure of the arterioles (critical closing pressure) responsible for pressure gradient driving peripheral venous return
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Vascular & Cardiac Function
Vascular function At a given MCFP as Central Venous Pressure , venous return If MCPF = CVP; venous return goes to 0 Cardiac function As central venous pressure increases, cardiac output increases due to both intrinsic & extrinsic effects
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Central Venous Pressure
The pressure in the central veins (superior & inferior vena cava) at the entry into the right atrium. Central venous pressure = right atrial pressure
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Vasomotor center Collection of neurons in the medulla & pons
Four major regions pressor center- increase blood pressure depressor center- decrease blood pressure sensory area- mediates baroreceptor reflex cardioinhibitory area- stimulates X CN Sympathetic vasoconstrictor tone due to pressor center input 1/2 to 2 IPS maintains normal arterial blood pressure
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Control of Blood Pressure
Rapid short term control involves the nervous systems effect on vascular smooth muscle Long term control is dominated by the kidneys- Renal-body fluid balance
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Control of Blood Pressure
Concept of Contents vs. Container Contents blood volume Container blood vessels Control of blood pressure is accomplished by either affecting vascular tone or blood volume
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Baroreceptors Spray type nerve endings in vessel walls
Especially abundant in Carotid Sinus & Arch of Aorta Stimulated when stretched Inhibits “Pressor Center” via IX X CN & NTS Net Effects Vasodiation & decreased cardiac output Carotid sinus reflex more sensitive to changing P than static P buffer function buffer changes in BP to changing blood volume lack of long term control due to adaptation resetting within 1-2 days
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Low Pressure Baroreceptors
Located in atrial walls & pulmonary arteries augment arterial baroreceptors minimize arterial pressure changes in response to blood volume changes
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Stretch on Atrial Wall Baroreceptor reflex- “low pressure”
decreased heart rate increased urine production decreased SNS in renal nerves decreased secretion of ADH Bainbridge reflex- increase heart rate Release of Atrial Natriuretic Peptide dirurectic, natriuretic, vasodilator
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Renal-Body Fluid System
Arterial Pressure (AP) Control Increased ECF will cause AP to rise In response the kidneys excrete excess ECF
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Determinants of long term AP
The degree of shift of the renal output curve for water and salt The level of the water and salt intake line Increased total peripheral resistance will not create a long term elevation of BP if fluid intake and renal function do not change
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Control of blood pressure
Most autoregulation of both renal blood flow and glomerular filtration takes place at the afferent arteriole Normal glomerular filtration rate is about 100 ml/min Normal renal blood flow is about 1.25 L/min (25% of Cardiac Output)
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The Kidney Afferent arterioles supply the glomerular capillaries where filtration takes place Efferent arterioles drain the glomerular capillaries and give rise to the peritubular capillaries where reabsorption takes place vasa recti specialized peritubular capillaries associated with juxtamedullary nephrons
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Renal control of blood pressure
When the extracellular fluid levels rises, the arterial pressure rises The kidney excretes more fluid, thus bringing the pressure back to normal SNS + causes renin secretion which causes the formation of angiotensin, which in turn stimulates release of Aldosterone from the adrenal cortex and ADH from the posterior pituitary All of the above promote increased blood pressure by either causing H2O reabsorption and/or vasoconstriction
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Role of afferent & efferent arterioles in autoregulation
In kidney constriction of afferent arterioles will decrease both renal Q and GFR constriction of efferent arterioles will decrease renal Q but increases GFR by creating back pressure therefore in the face of a rising arterial BP constriction of the afferent arterioles alone can autoregulate both Q and GFR (within limits)
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Hormones regulating RBF
Decrease renal blood flow (RBF) norepinephrine epinephrine angiotensin II Increase renal blood flow (RBF) prostaglandins (E & I)
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Tubuloglomerular feedback
Moniters NaCl in the Macula densa of the distal tubule NaCl in Macula densa + renin release from the Juxtaglomerular (JG) cells renin angiotensin II levels efferent arteriole resistance NaCl in Macula densa also causes dilatation of afferent arteriole
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Generation of hypertension
Tie off one renal artery development of systemic hypertension elevation of renin and angiotensin II no development of uremia Tie off one renal artery and remove kidney no development of hypertension or uremia Tie off and remove both kidneys development of both hypertension and uremia
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Circulatory Readjustments at Birth
Increased blood flow through lungs & liver pulmonary vascular resistance decreases decreased RVP, pulmonary arterial BP Loss of blood flow through the placenta doubles the systemic vascular resistance increased LAP, LVP, aortic BP Closure of Foramen Ovale, Ductus Arteriosis, & Ductus Venosus
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Circulatory Readjustments (cont)
Closure of Foramen Ovale due to reversal of pressure gradient between RA and LA, flap closes Closure of Ductus Arteriosis Reversal of flow from aorta to pulmonary artery, and increased oxygen levels cause constriction of smooth muscle Closure of Ductus Venosus cause unknown allows portal blood to perfuse liver sinuses
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Circulation in Fetus Right and Left Ventricle pump in parallel into the aorta Very little pulmonary blood flow Low pressure in aorta due to low TPR because of placenta-umbilical arteries Blood returning from the placenta via the umbilical veins bypass liver and flow directly into inferior VC via dutus venosus
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Circulation in Fetus In the fetus there exsits two right to left shunts for blood to bypass the lungs Foramen Ovale shunts most blood returning to the the heart from the inferior vena cava to the left atrium Ductus Arteriosus shunts most blood returning to the heart from the superior vena cava to the aorta
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Exercise Greatest stress on the CV system
Sympathetic nervous system orchestrates many of the changes associated with exercise Cardiac output is increased 5-6 fold Blood flow is shifted primarily from organs to active skeletal muscle
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The role of the SNS SNS stimulation due to: SNS effects
Cerebral cortex stimulation (central command) Reflex signals from active joint proprioceptors and muscle spindles Local chemoreceptor signals originating in the active muscle SNS effects Increased HR and SV (CO) Induces local metabolic vasodilatation at the heart
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SNS effects (cont) SNS stimulation of pre-capillary resistance vessels (organs and inactive skeletal muscle) decreases blood flow SNS stimulation of veins causes constriction which mobilizes blood out of veins increasing venous return Redistribution of blood volume SNS stimulation of vascular smooth muscle in walls of arteries help maintain slightly increased blood pressure during exercise
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Tissues that escape SNS vasoconstriction
Heart Brain Lungs
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Increased flow to active muscle
Increased blood flow to the active muscle is NOT mediated by the SNS but by the local release of tissue metabolites in response to the increase in metabolism “Local vasodilators” (partial list) Adenosine CO2 K+ Histamine Lactic acid
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Blood Flow Rest CO = 5.9 L/min Exercise = 24 L/min Coronary-250 ml/min
Brain-750 ml/min Organs-3100 ml/min Inactive muscle-650 ml/min Active muscle-650 ml/min Skin- 500 ml/min Exercise = 24 L/min Coronary-1000 ml/min Brain-750 ml/min Organs-600 ml/min Inactive muscle-300 ml/min Active muscle-20,850 ml/min Skin- initially↓, then ↑as body temp ↑
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CV changes during exercise
Cerebral cortical activation of the SNS SNS effects vasoconstriction of arterioles to flow to non active tissues (viscera) vasoconstriction of veins to MCFP which venous return stimulation of heart ( HR, SV) CO TPR due to vasodilatation in active muscle Increased O2 uptake which decreases VO2 AVO2 difference (AO2 stays relatively constant
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Effect of exercise on CV endpoints
HR ↑ ( b/min) SV ↑ to a point and then may ↓ CO ↑ (5-25 L/min) Systolic BP ↑ Diastolic BP ↑ (slightly) Mean arterial BP ↑ (slightly) Total peripheral resistance ↓ Oxygen consumption ↑ ( L/min) Arteriovenous oxygen difference ↑ (25-50%)
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AP changes during exercise
SBP due to the CO > TPR (also SNS contributes to ) DBP only slightly (and may ) Pulse Pressure (SBP-DBP)
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venous return during exercise
SNS constriction of veins Intermittent skeletal muscle activity coupled with one way valves in veins “venous pump” frequency & depth of respiration increased negative thoracic pressure
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VO2 Maximum The maximum volume of oxygen that one can take up from the lungs and deliver to the tissues/minute Can range from 1.5 L/min in a cardiac patient to 3.0 L/min in a sedentary man to 6.0 L/min or greater in an endurance athlete Function of CO and AV O2 difference Proportional to increases in SV as training occurs
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Pulmonary Physiology Respiratory neurons in brain stem
sets basic drive of ventilation descending neural traffic to spinal cord activation of muscles of respiration Ventilation of alveoli coupled with perfusion of pulmonary capillaries Exchange of oxygen and carbon dioxide
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Respiratory Centers Located in brain stem
Dorsal & Ventral Medullary group Pneumotaxic & Apneustic centers Affect rate and depth of ventilation Influenced by: higher brain centers peripheral mechanoreceptors peripheral & central chemoreceptors
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Muscles of Ventilation
Inspiratory muscles- increase thoracic cage volume Diaphragm, External Intercostals, SCM, Ant & Post. Sup. Serratus, Scaleni, Levator Costarum Expiratory muscles- decrease thoracic cage volume Abdominals, Internal Intercostals, Post Inf. Serratus, Transverse Thoracis, Pyramidal Under resting conditions expiration is passive and is associated with recoil of the lungs
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Movement of air in/out of lungs
Considerations Pleural pressure negative pressure between parietal and visceral pleura that keeps lung inflated against chest wall varies between -5 and -7.5 cmH2O (inspiration to expiration Alveolar pressure subatmospheric during inspiration supra-atmospheric during expiration Transpulmonary pressure difference between alveolar P & pleural P measure of the recoil tendency of the lung peaks at the end of inspiration
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Compliance of the lung V/P
At the onset of inspiration the pleural pressure changes at faster rate than lung volume-”hysteresis” Air filled lung vs. saline filled lung Easier to inflate a saline filled lung than an air filled lung because surface tension forces have been eliminated in the saline filled lung
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Collapse of the lungs If the pleural space communicates with the atmosphere, i.e. pleural P = atmospheric P, the lung will collapse Causes puncture of parietal pleura sucking chest wound erosion of visceral pleura also if a major airway is blocked the air trapped distal to the block will be absorbed by the blood and a segment would collapse
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Effect of Thoracic Cage on Lung
Reduces compliance by about 1/2 around functional residual capacity (at the end of a normal expiration) Compliance greatly reduced at high or low lung volumes
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Pleural Pressure Lungs have a natural tendency to collapse
surface tension forces 2/3 elastic fibers 1/3 What keeps lungs against the chest wall? Held against the chest wall by negative pleural pressure “suction”
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Pleural Fluid Thin layer of mucoid fluid
provides lubrication transudate (interstitial fluid + protein) total amount is only a few ml’s Excess is removed by lymphatics mediastinum superior surface of diaphragm lateral surfaces of parietal pleural helps create negative pleural pressure
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Surfactant Reduces surface tension forces by forming a monomolecular layer between aqueous fluid lining alveoli and air, preventing a water-air interface Produced by type II alveolar epithelial cells complex mix-phospholipids, proteins, ions dipalmitoyl lecithin, surfactant apoproteins, Ca++ ions
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Static Lung Volumes Tidal Volume Inspiratory Reserve Volume
amount of air moved in or out each breath Inspiratory Reserve Volume maximum vol one can inspire above normal inspiration Expiratory Reserve Volume maximum vol one can expire below normal expiration Residual Volume volume of air left in the lungs after maximum expiratory effort
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Static Lung Capacities
Functional residual capacity (RV+ERV) vol. of air left in the lungs after a normal expir., balance point of lung recoil & chest wall forces Inspiratory capacity (TV+IRV) max. vol. one can inspire during an insp effort Vital capacity (IRV+TV+ERV) max. vol. one can exchange in a resp. cycle Total lung capacity (IRV+TV+ERV+RV) the air in the lungs at full inflation
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Determination of RV, FRC, TLC
Of the static lung volumes & capacities, the RV, FRC, & TLC cannot be determined with basic spirometry. Helium dilution method for RV, FRC, TLC FRC= ([He]i/[He]f-1)Vi [He]i=initial concentration of helium in jar [He]f=final concentration of helium in jar Vi=initial volume of air in bell jar
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Determination of RV, FRC, TLC
After FRC is determined with the previous formula, determination of RV & TLC is as follows: RV = FRC- ERV TLC= RV + VC ERV & VC values are determined from basic spirometry VC, IRV, IC with restrictive lung conditions
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Pulmonary Flow Rates Compromised with obstructive conditions
decreased air flow minute respiratory volume RR X TV Forced Expiratory Volumes (timed) FEV/VC Peak expiratory Flow Maximum Ventilatory Volume
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Dead Space Area where gas exchange cannot occur
Includes most of airway volume Anatomical dead space (= 150 ml) airways Physiological dead space = anatomical + non functional alveoli FRC (2300 ml) - dead space (150 ml) = 2150 ml (alveolar vol.)
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Control of Airway Smooth Muscle
Neural control SNS-beta receptors causing dilatation direct effect weak indirect effect predominates function unclear Parasympathetic-muscarinic receptors causing constriction NANC nerves (non adrenergic, non cholenergic) inhibitory release VIP & NO bronchodilitation stimulatory bronchoconstriction, mucus secretion, vascular hyperpermeability, cough, vasodilation “neurogenic inflammation”
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Control of Airway Smooth Muscle (cont.)
Local factors histamine binds to H1 receptors-constriction histamine binds to H2 receptors-dilation slow reactive substance of anaphylaxsis-constriction-allergic response to pollen Prostaglandins E series- dilation Prostaglandins F series- constriction
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Control of Airway Smooth Muscle (cont)
Enviornmental pollution smoke, dust, sulfur dioxide, some acidic elements in smog elicit constriction of airways mediated by: parasympathetic reflex local constrictor responses
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Effect of pH on ventilation
Normal level of HCO3- = 25 mEq/L Metabolic acidosis (low HCO3-) will stimulate ventilation (regardless of CO2 levels) Metabolic alkalosis (high HCO3-) will depress ventilation (regardless of CO2 levels)
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Pulmonary circulation
Pulmonary artery wall 1/3 as thick as aorta RV 1/3 as thick as LV All pulmonary arteries have larger lumen more compliant operate under a lower pressure can accommodate 2/3 of SV from RV Pulmonary veins shorter but similar compliance compared to systemic veins
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Total Pulmonic Blood Volume
450 ml (9% of total blood volume) reservoir function 1/2 to 2X TPBV shifts in volume can occur from pulmonic to systemic or visa versa e.g. mitral stenosis can pulmonary volume 100% shifts have a greater effect on pulmonary circulation
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Systemic Bronchial Arteries
Branches off the thoracic aorta which supplies oxygenated blood to the supporting tissue and airways of the lung. (1-2% CO) Venous drainage is into azygous (1/2) or pulmonary veins (1/2) (short circuit) drainage into pulmonary veins causes LV output to be slightly higher (1%) than RV output & also dumps some deoxygenated blood into oxygenated pulmonary venous blood
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Pulmonary lymphatics Extensive & extends from all the supportive tissue of lungs & courses to the hilum & mainly into the right lymphatic duct remove plasma filtrate, particulate matter absorbed from alveoli, and escaped protein from the vascular system helps to maintain negative interstitial pressure which pulls alveolar epithelium against capillary endothelium. “respiratory membrane”
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Pulmonary Pressures Pulmonary artery pressure = 25/8
mean = 15 mmHg Mean pulmonary capillary P = 7 mmHg. Major pulmonary veins and left atrium mean pressure = 2 mmHg.
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Control of pulmonary blood flow
Since pulmonary blood flow = CO, any factors that affect CO (e.g. peripheral demand) affect pulmonary blood flow in a like way. However within the lung blood flow is distributed to well ventilated areas low alveolar O2 causes release of a local vasoconstrictor which automatically redistributes blood to better ventilated areas
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ANS influence on pulmonary vascular smooth muscle
SNS + will cause a mild vasoconstriction Parasympathetic + will cause a mild vasodilitation
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Oxygenation of blood in Pulmonary capillary
Under resting conditions blood is fully oxygenated by the time it has passed the first 1/3 of pulmonary capillary even if velocity 3X full oxygenation occurs Normal transit time is about .8 sec Under high CO transit time is .3 sec which still allows for full oxygenation Limiting factor in exercise is SV
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Effect of hydrostatic P on regional pulmonary blood flow
From apex to base capillary P (gravity) Zone 1- no flow alveolar P > capillary P normally does not exsist Zone 2- intermittant flow (toward the apex) during systole; capillary P > alveolar P during diastole; alveolar P > capillary P Zone 3- continuous flow (toward the base) capillary P > alveolar P During exercise entire lung zone 3
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Pulmonary Capillary dynamics
Starling forces (ultrafiltration) Capillary hydrostatic P = 7 mmHg. Interstitial hydrostatic P = -8 mmHg. Plasma colloid osmotic P = 28 mmHg. Interstitial colloid osmotic P = 14 mm Filtration forces = 15 mmHg. Reabsorption forces = 14 mmHg. Net forces favoring filtration = 1 mmHg. Excess fluid removed by lymphatics
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The lung as an organ of metabolism
As an organ of body metabolism the lung ranks second behind the liver. One advantage the lung has over the liver is the fact that all blood passes through the lungs with every complete cycle Some examples Angiotensin I converted to Angiotensin II Prostaglandins inactivated in one pass through pulmonary circulation
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Basic Gas Laws Boyle’s Law Avogadro’s Law Charles’ Law
At a constant T the V of a given quantity of gas is 1/ to the P it exerts Avogadro’s Law = V of gas at the same T & P contain the same # of molecules Charles’ Law At a constant P the V of a gas is to its absolute T The sum of the above gas laws: PV=nRT
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PV = nRT P=gas pressure V=volume a gas occupies
n= number of moles of a gas R= gas constant T= absolute temperature in Kelvin(C - 273)
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Additional Gas Laws Graham’s Law Henry’s Law
the rate of diffusion of a gas is 1/ to the square root of its molecular weight Henry’s Law the quantity of gas that can dissolve in a fluid is = to the partial P of the gas X the solubility coefficient Dalton’s Law of Partial Pressures the P exerted by a mixture of gases is = of the individual (partial) P exerted by each gas
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Atmospheric Air vs. Alveolar Air
H2O vapor 3.7 mmHg Oxygen 159 mmHg Nitrogen 597 mmHg CO mmHg H2O vapor 47 mmHg Oxygen 104 mmHg Nitrogen mmHg CO2 40 mmHg
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Diffusion across the respiratory membrane
Temperature Solubility Cross-sectional area sq root of molecular weight 1/ concentration gradient distance 1/ Which of the above are properties of the gas?
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Relative Diffusion Coefficients
These coefficients represent how readily a particular gas will diffuse across the respiratory membrane & is to its solubility and 1/ to sq. rt of MW. O CO CO N He
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Alveolar gas concentrations
[O2] in the alveoli averages 104 mmHg [CO2] in the alveoli averages 40 mmHg
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The respiratory unit Consists of about 300 million alveoli
Respiratory membrane 2 cell layers alveolar epithelium capillary endothelium averages about .6 microns in thickness total surface area sq. meters ml of pulmonary capillary blood
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Diffusing capacity of Respiratory Membrane
Oxygen under resting conditions 21 ml.min/mmHg mean pressure gradient of 11 mmHg. 230 ml/min increases during exercise Carbon dioxide diffuses at least 20X more readily than oxygen
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O2 & CO2 in expired air As one expires a normal tidal volume of 500 ml the concentrations of O2 & CO2 [O2] start high & fall toward the end of expiration ( mmHg) [CO2] start low & rise toward the end of expiration (0-40 mmHg) the first air expired is from the dead space the last 1/2 of expired air is from alveoli
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Alveolar air turnover Each normal breath (=tidal volume) turns over only a small percentage of the total alveolar air volume. 350/2150 Approximately 6-7 breaths for complete turnover of alveolar air. Slow turnover prevents large changes in gas concentration in alveoli from breath to breath
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Ventilation-Perfusion ratios
Normally alveolar ventilation is matched to pulmonary capillary perfusion at a rate of 4L/min of air to 5L/min of blood 4/5 = .8 is the normal V/P ratio If the ratio decreases, it is usually due to a problem with decreased ventilation If the ration increases, it is usually due to a problem with decreased perfusion of lungs
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Ventilation-Perfusion ratios
A decreased V/P ratio as ventilation goes to zero Alveolar PO2 will decrease to 40 mmHg Alveolar PCO2 will increase to 45 mmHg Results in an increase in “physiologic shunt blood”- blood that is not oxygenated as it passes the lung
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Ventilation-Perfusion ratios
An increased V/P ratio due to a decreased perfusion of the lungs from the RV Alveolar PO2 will increase to 149 mmHg Alveolar PCO2 will decrease to O mmHg Results in an increase of physiologic dead space- area in the lungs where oxygenation is not taking place “includes non functional alveoli”
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Transport of O2 & CO2 Oxygen- 5 ml/dl carried from lungs-tissue
Dissolved-3% Bound to hemoglobin-97% increases carrying capacity fold Carbon Dioxide- 4 ml/dl from tissue-lungs Dissolved-7% Bound to hemoglobin (and other proteins)-23% Bicarbinate ion-70%
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Blood pH Arterial blood (Oxygenated) Venous blood (Deoxygenated) 7.41
7.37 (slightly more acidic but buffered by blood buffers) In exercise venous blood can drop to 6.9
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Respiratory exchange ratio
Ratio of CO2 output to O2 uptake R= 4/5=.8 What happens to Oxygen in the cells converted to carbon dioxide (80%) converted to water (20%) As fatty acid utilization for E increases the percentage of metabolic water generated from O2 increases to a maximum of 30%. If only CHO are used for energy no metabolic water is generated from O2, all O2 is converted to CO2
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Oxy-Hemoglobin Dissociation
As Po2 , hemoglobin releases more oxygen Po2 = 95 mmHg 97% saturation (arterial) Po2 = 40 mmHg 70% saturation (venous) Sigmoid shaped curve with steep portion below a Po2 of 40 mmHg slight in Po2 large release in O2 from Hgb Shift to the right (promote dissociation) increase temperature increase CO2 (Bohr effect) decrease pH increase 2,3 diphosphoglycerate (2,3 DPG)
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Carbon Dioxide carried in form of bicarbinate ion (70%)
CO2 + H2O H2CO3 H+ + HCO3- carbonic anhydrase in RBC catalyses reaction of water and carbon dioxide carbonic acid dissociates into H+ & HCO3 - Chloride shift As HCO3- leaves RBC it is replaced by Cl - Bound to hemoglobin (23%) reacts with amine radicals of hemoglobin & other plasma proteins Dissolved CO2 (7%)
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Neural control of ventilation
Goals of regulation of ventilation is to keep arterial levels of O2 & CO2 constant The nervous system adjusts the level of ventilation (RR & TV) to match perfusion of the lungs (pulmonary blood flow) By matching ventilation with pulmonary blood flow (CO) we also match ventilation with overall metabolic demand
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Neural control of ventilation
Dorsal respiratory group located primarily in the nucleus tractus solitarius in medulla termination of CN IX & X receives input from peripheral chemoreceptors baroreceptors receptors in the lungs rhythmically self excitatory ramp signal excites muscles of inpiration Sets the basic drive of ventilation
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Neural control of ventilation
Pneumotaxic center dorsally in N. parabrachialis of upper pons inhibits the duration of inspiration by turning off DRG ramp signal after start of inspiration Ventral respiratory group of neurons located bilaterally in ventral aspect of medulla can + both inspiratory & expiratory respiratory muscles during increased ventilatory drive Apneustic center (lower pons) functions to prevent inhibition of DRG under some circumstances
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Neural Control of Ventilation
Herring-Breuer Inflation reflex stretch receptors located in wall of airways + when stretched at tidal volumes > 1500 ml inhibits the DRG Irritant receptors-among airway epithethium + sneezing & coughing & possibly airway constriction J receptors - in alveoli next to pulmonary caps + when pulmonary caps are engorged or pulmonary edema create a feeling of dyspnea
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Chemical Control of Ventilation
Chemosensitive area of respiratory center Hydrogen ions-primary stimulus but can’t cross membranes (blood brain barrier-BBB) carbon dioxide-can cross BBB inside cell converted to H+ rises of CO2 in CSF- effect on + ventilation faster due to lack of buffers compared to plasma unresponsive to falls in oxygen-hypoxia depresses neuronal activity 70-80 % of CO2 induced increase in vent.
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Chemical Control of Ventilation
Peripheral Chemoreceptors aortic and carotid bodies 20-30% of CO2 induced increase in vent. Responsive to hypoxia response to hypoxia is blunted if CO2 falls as the oxygen levels fall responsive to slight rises in CO2 (2-3 mmHg) but not similar falls in O2 sensitivity altered by CNS SNS decreasing flow-increased sensitivity to hypoxia
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Respiratory adjustments at birth
Most important adjustment is to breath normally occurs within seconds stimulated by: cooling of skin slightly asphyxiated state (elevated CO2) mmHg of negative pleural P necessary to open alveoli on first breath
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Glomerular Filtration and Renal blood flow
Renal Physiology Glomerular Filtration and Renal blood flow
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Renal Clearance The Amount of a substance in urine reflects 3 processes Glomerular filtration Reabsorption of the substance from the tubule back into blood Secretion of the substance from the blood into the tubular fluid Excreted=filtered – reabsorbed + secreted
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Renal Clearance Represents the volume of plasma from which all the substance has been removed and excreted into the urine per unit time Cx = (Ux) (V)/ Px (example in parenthesis) Cx = clearance from the plasma (100 ml/min) V = Urine flow (1 ml/min) Pa = Plasma concentration (1mg/ml) Ux = urine concentration (100 mg/min)
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Measurement of GFR Clearance of Inulin = GFR
Polyfructose molecule (m.w. 5000) Freely filtered at glomerulus Not reabsorbed or secreted Amount excreted in urine/min = amount filtered at glomerulus/min = GFR Average GFR = 125 ml/min (7.5 L/hr or L/day)
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Filtration Fraction Not all plasma coming into the kidney and the glomerulus is filtered Filtration Fraction (FF) = GFR/RPF GFR= glomerular filtration rate RPF= renal plasma flow FF averages
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Filtration + Reabsorption
Clearance of Glucose Glucose is freely filtered at the glomerulus Filtered Load (FL) of glucose = GFR X Pg Pg = [glucose]plasma Glucose is reabsorbed from the tubular fluid by cells of the proximal tubule Tubular transport maximum for glucose averages 375 mg/min FL < 375 mg/min; all glucose reabsorbed, 0 clearance FL > 375 mg/min; some glucose in urine, some clearance
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Filtration + Secretion
Clearance of PAH (p-Aminohippuric acid) PAH is an organic acid excreted into the urine by glomerular filtration and tubular secretion (proximal tubule) Total excretion = filtered load + secretion Transport Maximum for proximal tubule (PT) secretion averages 80 mg/min Delivery to PT < 80 mg/min: all is secreted Delivery to PT > 80 mg/min: excess returned to circulation
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Physiology of body fluids
Total body water = (.6) body weight (42 L) ECF 1/3 (14 L) Interstitial fluid ¾ of ECF L Plasma ¼ of ECF L Major Cations- Na+ Major Anions- Cl- ICF 2/3 (28 L) Major cations- Ca++, Mg++, K+ Major Anions- Po4=, Protein, organic anions
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Osmolarity vs. Osmolality
Osmolarity = # of solute particles/ L H2O Temperature dependent Osmolality = # of solute particles/ Kg H2O Temperature independent In dilute solutions difference is insignificant
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Tonicity Tonicity of a solution is related to its effect on the volume of a cell Solutions can have: No effect- isotonic Increase volume “swelling” – hypotonic Decrease volume “shrinking” – hypertonic Related to osmolality and permeability of a solute across the membrane To exert osmotic effects a solute must not cross the cell membrane
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Oncotic Pressure Oncotic pressure is osmotic pressure generated by large molecules (especially proteins) in a solution Not a major force in considering movement of water across cell membranes Is a force for fluid movement across capillary wall, especially the glomerulus
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Specific Gravity The total solute concentration in a solution can also be measured as specific gravity Ratio of weight of a solution to an equal volume of distilled water (sg of distilled water =1gm/ml)
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Volumes of Body Fluid Compartments
Total body water = .6 X body weight (42L) ECF = .2 X body weight = 14 L (1/3) Interstitial Fluid 10.5 L (3/4 of ECF) Plasma 3.5 L (1/4 of ECF) ICF = .4 X body weight = 28 L (2/3) Volume = amount/concentration Total body water – tritiated water ECF – inulin, mannitol Plasma – tritiated albumin
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Capillary Fluid Exchange
Starling forces Capillary hydrostatic pressure Capillary oncotic pressure Interstitial hydostatic pressure Interstitial oncotic pressure Filtration coefficient of Capillary wall
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Cellular fluid exchange
Fluid volume = osmoles fluid osmolality Addition of 2 L of isotonic NaCl to ECF Increase ECF by 2 L, ICF stays constant Addition of 2 L of H2O to ECF (2/3 1/3) Figure out new fluid osmolality, solve for vol Addition of 290 mmoles of NaCl to ECF Adds 580 mOsm to ECF, pulls fluid from ICF
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Innervation of the Kidney
Sympathetic nerve fibers primarily from the celiac plexus (No parasympathetic) Fibers release norepinephrine and dopamine SNS innervated smooth muscle of afferent and efferent arterioles release renin in response to SNS + SNS + of nephron enhances sodium reabsorption
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Innervation of the Bladder
Important in controlling urination Smooth muscle of the bladder neck innervated by SNS from hypogastric nerves (alpha receptors- constriction) Bladder body innervated by Para fibers from pelvic N cause sustained bladder contraction Sensory fibers innervate the fundus Pudendal N innervate skeletal ms. Fibers of external sphincter causing contraction
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Micturition Act of emptying the urinary bladder Two processes
Filling of bladder to a critical level causes it to contract, Neuronal reflex (micturition reflex) Autonomic spinal cord reflex that can be inhibited or facilitated by brain stem and higher centers, eg. Cortex sensory signals reflexively cause para stimulation of detrusor muscle opening bladder neck, allowing urine to flow Process is completed by voluntarily relaxing the external sphincter
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Renal transport Reabsorption-net transport from tubular lumen into the blood-key element in solute reabsorption is Na+/K+ ATPase Secretion-net transport from the blood into the tubular lumen Proximal tubule Reabsorbs 67% of filtered H2O, Na+, Cl- and other solutes Nearly all filtered glucose and amino acids Secretes organic cations and anions (metabolic products) Loop of Henle Reabsorbs 20% of filtered Na+, Cl-, K+, as well as Ca++, HCO3- and Mg++. 20% of H2O absorbed exclusively by descending thin limb Distal tubule & collecting duct Reabsorbs 12% of filtered Na+ and Cl-, variable amounts of H2O Secretes variable amounts of K+ & H+
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Hormones from Anterior Pituitary
Prolactin (leuteotropic) hormone stimulates the production of milk up regulator of immune function Adrenocorticotropic (ACTH)hormone development of adrenal glands production of cortisol Follicle Stimulating Hormone (FSH) stimulates gametogenesis (ova & testes)
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More hormones from Ant. Pit
Luteinizing hormone (LH) + production of sex hormones from gonads stimulates ovulation & development of corpus luteum Growth hormone or somatotrophin (GH) + growth Thyrotrophin (TSH) + development of thyroid gland and + secretion of thyroxine Melanocyte stimulating hormone (Melanotrophin) + pigmentation
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Hypothalamic hormones
Oxytocin produced in paraventricular nucleus stored and released from posterior pituitary milk let down stimulates uterine contraction Vasopressin/ADH (Antidiurectic hormone) produced in supraoptic nucleus stored & released from posterior pituitary renal reabsorption of water vasoconstriction
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Hypothalamic factors Releasing factors stimulate secretion of anterior pituitary hormones via hypothalamic-hypophyseal portal system anything ending in liberin eg. somatoliberin Inhibitory factors are just the opposite of above anything ending in statin. e.g. somatostatin inhibits secretion of growth hormone Dopamine inhibits release of prolactin
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Thyroid/parathyroid Thyroxine (T3 & T4)from the thyroid gland
growth, metabolism Calcitonin (TCT) from the thyroid gland decreases plasma calcium decreases bone breakdown Parathormone (PTH) from dark chief cells of parathyroid gland increases plasma calcium increase growth
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Adrenal Gland Cortisol - from Zona Faciculata (cortex)
Increases blood glucose Increases metabolism Decreases immune response Aldosterone-Zona Glomerulosa-(cortex) Increases renal reabsorption of sodium and renal excretion of potassium & H+ Increases blood pressure
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Pancreas Hormone Insulin from Beta cells- Pancreas
Decrease blood glucose Glucagon - from Alpha cells - Pancreas Increase blood glucose
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Kidney hormones Somatomedin - from kidney & Liver
Stimulate growth Decrease blood glucose Vitamin D - from liver plus kidney Increase plasma calcium Increase growth Erythropoietin -from kidney Increase production of RBC’S
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Sex Hormones/Gonadal/males
Androgens - from interstitial cells of leydig -Testes Increase male phenotypic characteristics Stimulate growth
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More Sex hormones/gonads/female
Estrogens - from corpus luteum & placenta Stimulates female characteristics Stimulate birth process -contraction of uterus Stimulate growth Progesterone - from corpus luteum Stimulate female characteristics Decrease uterine contraction
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Other important hormones
Beta Endorphins - Ant. Pit, Hypothalmus Decrease pain Angiotensin II –Converted from Angio I in lungs by converting enzyme Increase secretion of aldosterone Stimulate vasocontriction Melatonin - from Pineal gland Increase immune response & sleep Pheromones Reacts to external stimuli, stimulates aggression, sexual attraction
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Gastrointestinal Physiology
Ingestion Digestion Absorption Regulation of GI function
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Ingestion-Chewing Chewing functions to: Mix food with saliva
Reduces size of food particles Facilitates swallowing Mixes CHO with salivary amylase Begins CHO digestion
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Ingestion-Swallowing
Voluntary Phase – oral phase Initiated in the mouth when tongue forces a bolus of food back toward the pharynx which contain a high density of somatosensory receptors Involuntary Phase – pharyngeal & esophageal Reflex arc receptors located near pharynx send signal via IX & X CN Motor output from MO to striated muscle of pharynx & upper esophagus Pharyngeal Soft palate pulled upward, epiglottis closes off larynx, upper esophageal sphincter relaxes, peristalsis initiated Esophageal (lower 2/3 smooth muscle) Peristaltic waves (1-2) to clear esophagus
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Digestion physiology Alimentary tract provides the body with a continual supply of water, electrolytes, nutrients In order to do this requires: ingestion of food Movement of food through the digestive tract Secretion of digestive juices Digestion and absorption Circulation of blood through the GI organs Control of these functions by the neuroendocrine system
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Peristalsis Controlled by the enteric nervous system
Myenteric plexus which lies between circular and smooth muscle layers Increased activity results in Increased tone Increased intensity of rhythmic contractions Increased rate (slight) Increased velocity which creates more rapid peristaltic waves Parasympathetic-Acetylcholine excites SNS-Norpinephrine/Epinephrine will inhibit
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Hormones of the gut Cholecystokinin Secretin
Secreted by “I” (APUD) cells from mucosa of duodenum/jejunum in response to breakdown products of fats Increased contractility of the gallbladder to release bile which emulsifies fats Inhibits stomach motility Secretin Secreted by “S” (APUD) cells from mucosa of duodenum in response to acidic gastric juice Mild inbitory effect on gut motility Inhibits gastrin secretion
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Hormones of the Gut Gastrin Stimulates gastric acid [H+] secretion
Stimulates pancreatic enzyme secretion Gall bladder contraction Gastrin is stimulated by PNS, proteins, gut distension, and inhibited by acids and secretin Gastric inhibitory peptide (GIP) Stimulation of insulin secretion Secreted in response to all 3 types of nutrients Glucose, AA, FA Secreted by duodenal and jejunal mucosa
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Paracrines Synthesized in endocrine cells of GI tract
Act locally via diffusion Somatostatin Secreted in response to low pH Inhibits secretion of other GI hormones Inhibits gastric H+ secretion Histamine H+ secretion
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