Chapter 62 .pptx

UNIT 11 Chapter 62: Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism Slides by Thomas H. Adair, PhD © 2011 byan Saunders, an of imprint of Elsevier Copyright © 2021 Copyright by Saunders, imprint Elsevier Inc.Inc. Cerebral blood flow • Anatomy – • Blood flow supplied by 4 arteries:...

UNIT 11 Chapter 62: Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism Slides by Thomas H. Adair, PhD © 2011 byan Saunders, an of imprint of Elsevier Copyright © 2021 Copyright by Saunders, imprint Elsevier Inc.Inc. Cerebral blood flow • Anatomy – • Blood flow supplied by 4 arteries: internal carotid and vertebral arteries. • Circle of Willis (safety mechanism) • • • • • Brain is highly dependent upon blood flow and oxygen delivery. Very little anerobic metabolism. Cessation of flow for 5-10 s results in loss of consciousness. CBF* is 15% of resting cardiac output; only 2% of body weight. Hence, high metabolic rate. CBF is tightly regulated to meet the brain's metabolic demands. CBF can be measured using functional magnetic resonance imaging and positron emission tomography. CBF is controlled by metabolic factors: CO2, H+, O2, and substances from astrocytes. *CBF (cerebral blood flow) is blood supply to brain. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. The brain uses glucose for energy and almost nothing else. Glucose delivery to brain is not insulin dependent (unlike nearly all other tissues). So, brain virtually always gets plenty of glucose (when there is glucose in the blood). Insulin mobilizes GLUT4 glucose transporters to plasma membrane in most tissues, but not brain. However, over treatment of diabetics with insulin, causes blood glucose to fall to low levels. The decrease in brain glucose levels can lead to psychotic disturbances and coma. Brain has ~2 min supply of glucose (glycogen in neurons). Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Increased neuronal activity leads to increased blood flow Figure 62-3 Light shining in eyes (of cats) for 30 seconds caused a 40% increase in occipital blood flow. Compare blood flow and capillarity in gray matter and white matter. Which is greater? Copyright © 2011 by Saunders, an imprint of Elsevier Inc. hy pe rv en til at How does increased arterial CO2 cause vasodilation? • CO2 diffuses into brain tissue, raising local H+ ion concentration. • H+ ions cause vasodilation. io n Blood flow control: CO2 and H+ Figure 62-2 Recall that hyperventilation causes brain hypoxia for two reasons: (1) increased neuronal activity, and (2) decreased CBF What does this tell you about BF (vasoconstriction). control? Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Role of astrocytes in blood flow control • Many studies have suggested a role for astrocytes in matching blood flow to neuronal activity in brain. • The theory is the following: – Increased nervous activity leads to increased glutamate spillover at synapses. – The glutamate triggers an astrocytic calcium wave. – The astrocytic calcium wave leads to release of vasodilatory prostaglandins (PGs), which cause arterioles to dilate. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. utoregulation of cerebral blood flow CBF is autoregulated extremely well over a pressure range of 60 mm Hg to 140 mm Hg as shown. Above 160 mm Hg: blood flow increases with increasing pressure, but most importantly, the blood vessels begin to stretch. This stretch can lead to damage and The mechanism of cerebral autoregulation is poorly eventual rupture (stroke). Figure 62-4 understood. Probably involves different mechanisms for increased and decreased pressures. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Cerebrospinal Fluid (CSF) 1 • CSF performs a cushioning function. Brain floats in CSF. 8 Subarachnoid space 7 • Volumes: cranial vault, 1600 mL; 2 CSF, 150 mL. 3 Production, flow path, reabsorption: 500 mL CSF formed each day (mainly) by choroid plexus in lateral ventricles. Flow path is shown Figure 62-5 (1-8). 4 5 6 Cisterna magna 8 CSF enters venous system through one-way valve-like pores in arachnoidal villi. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. CSF production by choroid plexus Mechanism of fluid secretion: Active transport of Na+ by epithelial cells; Cl - follows Na+; immediate osmosis of water. Composition: clear, colorless, similar to plasma (but not the same). • Osmotic pressure (like plasma) • Na+ concn (slightly less than plasma) • Cl – concn (~15% higher than plasma) • K + concn (40% of that of plasma). Figure 62-6 • Glucose (~30% of that of Choroid plexus in a lateral ventricle. plasma). • Plasma proteins (1-2% of that Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Drainage of perivascular space Figure 62-7 Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Subdural Hematoma - Intracranial pressure (ICP) (8-15 mm Hg) Trauma Tumor Infection Venous compression ↑ICP Edema ↑Pc • Cranium has fixed volume: 1500-1600 mL. • ICP assessed clinically by extent of optic disk protrusion (papilledema). • Increased ICP leads to loss of CSF and reduction in venous volume to compensate for increases in brain volume. Ultimately, this process becomes exhausted. • Increased ICP can compress veins, and hence, can increase capillary hydrostatic pressure, causing brain to swell. • High ICP causes herniation of brain, distortion and pressure on cranial nerves as well as vital neurological centers. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Blood brain barrier (BBB) - General • Function • BBB protects brain from blood borne toxins and sudden changes in blood chemistry. • Permeability • Permeable to water, gases (N2, O2, CO2), and small lipid molecules by passive diffusion. • Selective transport of glucose and amino acids crucial to neural function. Types of Capillaries • Structure us o d • Prevents entry of potential neurotoxins (e.g., ubotulinum s tetoxin). tinu • Brain ra endothelial cells form BBB. o t u s on e c in t n s n Barrier also includes thick Di Fe Co basement membrane and astrocytic end-feet. • Brain has continuous type of capillaries with tight junctions between cells. • Tight junctions unique to Fat Liver Intest villi capillaries in brain Muscle / skin Bone Endo glands Nervous sys marrow • Substances entering brain must Kidney glom spleen move through endothelial cell membrane. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Blood brain barrier (BBB) Tight Junctions Tight Junctions Capillary Nucleus EC Tight junction Purves et al, Neuroscience, 2012 (Fig A20) Astrocyte foot process Tight junction Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Blood brain barrier (BBB) – Transport How do substances pass through BBB? 1. Small lipophilic: drugs, oxygen and carbon dioxide diffuse across the BBB. 2. Ions: require ATPdependent transporters such as (Na++K+)ATPase; Na+-2Cl--K+ transporter 3. Nutrients: Glucose (GLUT1); Lactate (MCT1); Amino acids (many transporters) 4. Peptides: encephalins, vasopressin, insulin. 1 2 4 3 GLUT-1: facilitated glucose transporte r Nature Reviews Neuroscience 12, 723-738 (December 2011) Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Blood brain barrier (BBB) - Clinical Damage to BBB can be caused by: • Hypoxia • Systemic inflammation: antibiotics and phagocytes can move across the BBB. (normally, antibodies cannot cross BBB). • Harmful bacteria: gain access by releasing cytotoxins like pneumolysin Drug movement through BBB: • Clinical challenge • AIDs virus hides behind BBB. • Drugs are being designed to cross BBB via increased lipid solubility. • Hypertonic mannitol can increase BBB permeability. Question: How can hypertonic solutions of mannitol increase permeability of BBB? Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Stroke (cerebrovascular accident, CVA) • Two types of stroke: – Ischemic (87%): interruption of blood supply – Hemorrhagic (13%): rupture of blood vessel. • Causes of ischemic stroke – Thrombosis (blood clot formed locally) – Embolism (blood clot from elsewhere) – Systemic (shock) Most commonhypotension cause is thrombosis – Venous thrombosis (dural venous caused by arteriosclerotic plaques in sinuses) feeder arteries to brain. Neurological effects are dictated by area of brain affected. CT scan slice of brain showing a righthemispheric ischemic stroke (left side of image). Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Neurophysiology Review 2023 Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Increased neuronal activity leads to increased blood flow Figure 62-3 Light shining in eyes (of cats) for 30 seconds caused a 40% increase in occipital blood flow. Compare blood flow and capillarity in gray matter and white matter. Which is greater? Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Stroke (cerebrovascular accident, CVA) • Two types of stroke: – Ischemic (87%): interruption of blood supply – Hemorrhagic (13%): rupture of blood vessel. • Causes of ischemic stroke – Thrombosis (blood clot formed locally) – Embolism (blood clot from elsewhere) – Systemic hypotension (shock) – Venous thrombosis (dural venous sinuses) Most common cause is thrombosis caused by arteriosclerotic plaques in feeder arteries to brain. Neurological effects are dictated by area of brain affected. CT scan slice of brain showing a right-hemispheric ischemic stroke (left side of image). Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Subdural Hematoma - Intracranial pressure (ICP) (8-15 mm Hg) Trauma Tumor Infection Venous compression ↑ICP Edema ↑Pc • Cranium has fixed volume: 1500-1600 mL. • ICP assessed clinically by extent of optic disk protrusion (papilledema). • Increased ICP leads to loss of CSF and reduction in venous volume to compensate for increases in brain volume. Ultimately, this process becomes exhausted. • Increased ICP can compress veins, and hence, can increase capillary hydrostatic pressure, causing brain to swell. • High ICP causes herniation of brain, distortion and pressure on cranial nerves as well as vital neurological centers. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Neuron Structure 3 major components: • Soma - main body of neuron. • Axon - extends from soma to synaptic terminal. - the effector part of neuron. • Dendrite - projections from soma. - the sensory portion of neuron. Figure 461 Small molecule, rapidly acting transmitters Usually excitatory in CNS Usually inhibitory Function: Mediates most acute responses of nervous system. GABA: Chief inhibitory transmitter in CNS Glycine: inhibitory transmitter, mainly in cord Glutamate: Chief excitatory transmitter in CNS. Accounts for >90% of the synaptic connections in CNS. Synthesized on demand; does not use vesicles – diffuses through membrane Table 45-1 Facilitation at the squid giant synapse A Presynaptic Membrane Potential (mV) 0.5 Ca++ concentration in synaptic end of neuron 0.4 Amount of facilitation Action potentials 0.3 Facilitation B Postsynaptic Membrane Potential (mV) EPSPs 0.2 0.1 0.0 0 10 20 Time (ms) 30 0 10 20 30 40 50 Interval between stimuli (ms) Redrawn after Purves, Neuroscience. 5th ed., Sinauer, 2012. Facilitation: • Definition – The increased transmitter release produced by an action potential that follows closely upon a preceding action potential. Note: This is not temporal summation. • Mechanism – prolonged elevation of presynaptic calcium levels following synaptic activity. Electrotonic potentials EPSP = +20 mV IPSP = -5 mV Figure 45-9 How can hyperventilation induce seizures? Low CO2 in brain can cause "spontaneous and asynchronous firing of neurons“ affecting virtually all mental and psychological abnormalities ranging from panic attacks and seizures to sleeping problems, depression and schizophrenia. Mechanism: Hyperventilation → ↓CO2 → ↓blood flow → ↓O2 → ? → seizures So, hyperventilation causes brain hypoxia for two reasons: (1) increased neuronal activity, and (2) decreased CBF (vasoconstriction). Types of Sensory Receptors • Mechanoreceptors - detect deformation • Thermoreceptors - detect change in temperature • Nociceptors - detect damage (pain receptors) • Electromagnetic - detect light Noci - is derived from the Latin term for “hurt” • Chemoreceptors - taste, smell, CO2, O2 etc. Adaptation of Receptors (cont.) • Rate of adaptation varies with type of receptor. • Therefore, receptors respond when a change is taking place. (i.e., think of the feel of clothing on your skin) Adapted from Kandel, Schwartz And Jessell 4th addition 2000 Rapidly adapting Slowly adapting Rapidly adapting Slowly adapting Mechanism of Adaptation - varies with the type of receptor. • Mechanoreceptors – fluid redistribution in Pacinian corpuscle decreases distorting force. • Photoreceptors – the amount of light sensitive chemicals is changed. Relationship between receptor potentials and action potentials - APs occur when receptor potential rises above threshold - Increased stimulus intensity causes increased receptor potential, which increases AP frequency. Figure 47-2 Divergence in neuronal pathways Figure 47-11 Amplifying type of divergence. Signal is transmitted in two directions. Example: single pyramidal cell in motor cortex can stimulate several hundred Example: information from dorsal columns of spinal cord takes two directions (1) cerebellum, (2) thalamus Reverberatory circuits (cont.) This is positive feedback - What stops it? fatigue of synaptic junctions What is the mechanism of fatigue? A. Transmitter depletion B. Receptor inactivation C. Abnormal ion concn in axon D. All of the above Sensory homunculus Homunculus – (latin) little human Figure 47-7 Lateral inhibition improves two-point discrimination Lateral inhibition present Figure 48-10 • Lateral inhibition is the capacity of an excited neuron to reduce activity of neighboring neurons; it improves degree of contrast – Occurs at every synaptic level (for dorsal column system): dorsal column nuclei, ventrobasal nuclei of thalamus, cortex Lesions of somatosensory cortex • Destruction of somatosensory area I results in: – loss of vibration, fine touch, and proprioception. – discrete localization ability. – inability to judge the degree of pressure. – inability to determine the weight of an object. – inability to judge texture. Also: – Hemineglect (unilateral neglect, hemispatial neglect or spatial neglect): patients are unaware of items to one side of space. – Astereognosis: inability to recognize objects by touch – Agraphesthesia: a disorientation of the skins sensation across its space (e.g., hard to identify a number or letter traced on the hand) Figure 47-7 Dorsal Column-medial lemniscal System • Contains large myelinated nerve fibers (30-110 m/sec). A-beta • Three neurons to sensory cortex / decussates in medulla oblongata • High degree of spatial orientation maintained throughout the tract . • Transmits information rapidly and with a high degree of spatial fidelity (ie. discrete types of mechanoreceptor information). • Transmits touch, vibration, position, fine pressure. Figure 48-3 The Anterolateral System • Contains smaller myelinated and unmyelinated fibers for slow transmission (0.5-40 m/sec). (Adelta, C) • three neurons to sensory cortex / decussates in spinal cord • low degree of spatial orientation. • transmits a broad spectrum of modalities. • pain, thermal sensations, crude touch and pressure, tickle and itch, sexual sensations. Figure 47-13 • • • Hyperalgesia: altered perception of pain such that stimuli which would normally induce a trivial discomfort causes significant pain. Often caused by damage to nociceptors or peripheral nerves. Tic Douloureux (painful tic): (aka, trigeminal neuralgia) disorder of trigeminal nerve (5th CN) can cause paroxysmal (sudden onset) facial pain. Can be triggered by touch or cold. Late onset: 60-70’s. Level of injury Brown-Sequard syndrome: Ipsilateral symptoms: loss of motor function (i.e. hemiparaplegia), vibration sense, fine touch proprioception (position sense), two-point discrimination, and weakness. Contralateral symptoms: loss of pain, temperature sensation, and crude touch. Hemiparaplegia: paralysis of one side of lower half of the body Dark area shows injury Referred Pain from visceral sources • Visceral tissues have few pain fibers. • Hence, highly localized organ damage causes little pain; however, widespread damage can cause severe pain. • Common causes of visceral pain – ischemia. – chemical irritation. – spasm of a hollow viscus. – over-distension of a hollow viscus. • Often, pain from internal organ is perceived to originate from a distant area of skin. • Mechanism: intermingling of second order neurons in dorsal horn of spinal cord from skin and viscera as shown. These are pain fibers Figure 49-5 Dual Pain Pathways 1. Fast pain (first pain) a. transmitted by type A-delta fibers (velocity 6-30 m/sec). b. transmitted in neospinothalamic tract 2. Slow pain (second pain) c. transmitted by type C fibers (0.5 - 2 m/sec). d. transmitted in the paleospinothalamic tract. Ad fiber C fiber 1st pain 2nd pain Subjective perception of pain time Because of these dual pathways, a double sensation of pain often occurs: sharp pain followed seconds later by slow pain. Neospinothalamic Tract Fast, sharp pain: A-delta fiber • On entering cord, pain fibers may travel up or down 1-3 segments and terminate on neurons in dorsal horn. • Glutamate is excitatory transmitter of A-delta pain fiber nerve ending. • 2nd neuron crosses immediately to the opposite side and passes to the brain in the anterolateral columns. • Some neurons terminate in the reticular substance but most go all the way to the ventrobasal complex of the thalamus. • 3rd order neurons go to the cortex. • Fast, sharp pain can be localized well when other tactile receptors are simultaneously stimulated. Figure 49-2 Figure 49-3 Paleospinothalamic Tract Slow, burning pain: C fiber • Type C pain fibers terminate in laminae II & III of spinal cord. • 2nd neuron crosses immediately to the opposite side and passes to the brain in the anterolateral columns. • Substance P is excitatory transmitter of type C pain fiber nerve ending. • • Only 10 to 25 % of fibers terminate in thalamus. Most terminate diffusely in reticular nuclei of medulla, pons and mesencephalon; tectal area of mesencephalon; periaqueductal gray region. • Poor localization of slow pain, often to just the affected limb or part of body. Figure 49-2 Figure 49-3 efractive Power of the eye - Diopter • • 2/3 of refractive power of eye results from anterior surface of cornea. This refraction is virtually eliminated when swimming under water since water has refractive index close to that of cornea; hence, you get a blurry image underwater. Lens has less refractive power, but it’s adjustable. – a diopter is a measure of the power of a lens. – 1 diopter is the ability to focus parallel light rays at a distance of 1 meter. – the retina is considered to be 17 mm behind refractive center of eye. – hence, the eye has a total refractive power of 59 diopters (1000/17). 1000/17 = 59 diopters 17 mm Guyton, Figure 50-8 Guyton, Figure 50-9 Accommodation • Refractive power of lens is 20 diopters. • Refractive power can be increased to 34 diopters by making lens thicker; this is called accommodation. • Accommodation is necessary to focus image on retina. • A relaxed lens is almost spherical in shape. • Lens is held in place by suspensory ligaments (zonule fibers) which under normal resting conditions causes the lens to be almost flat. • Contraction of ciliary muscle attached to ligament pulls ligament forward causing lens to become thicker (which increases refractive power of lens). • Under control of parasympathetic nervous system. Guyton, Figure 50-8 Guyton, Figure 50-10 Presbyopia: The inability to Accommodate; caused by denaturation of proteins in lens, making lens less elastic Power of accommodation decreases with age: Child, 14 diopters (34-20) 50 years old, 2 Cataracts leading cause of blindness worldwide • Cataracts – cloudy or opaque area of the lens caused by coagulation of lens proteins – Accounts for about half the cases of blindness in the world. – UV solar radiation is major factor in production of cataracts Surgical implantation of plastic lens can usually restore vision. ~6 million per year. Signal Transmission in the Retina • • • Transmission of signals in retina is by electrotonic conduction. Allows graded response proportional to light intensity. Only ganglion cells have action potentials. – send signals to brain. – spontaneously active with continuous action potentials. – visual signals are superimposed on this background. – many excited by changes in light intensity. – respond to contrast borders, this is the way the pattern of the scene is transmitted to the brain. Figure 51-12 Lateral Inhibition Processing the visual image begins in the retina. One example is lateral inhibition. • • • • Enhances visual contrast. Horizontal cells provide inhibitory feedback to rods and cones and bipolar cells. Output of horizontal cells is always inhibitory. Prevents lateral spread of light excitation on retina. Contrast is enhanced with excitatory center and inhibitory surround. Guyton, Figure 51-12 Guyton, Figure 51-13 The Optic Disc (also called the optic nerve head) What is it? • point where ganglion cell axons (~1 million) exit the eye to form the optic nerve (2nd cranial nerve). • entry point for retinal blood vessels • creates a blind spot since there are no rods or cones. • located 3-4 mm to nasal side of fovea. • size: 1.76mm (horizontally) x 1.92mm vertically • Has a central depression called the optic cup edematous optic disc Aka, papilledema Vitamin A1 is required for Phototransduction Vitamin A1 (aka, all-trans retinal) is converted into 11-cis retinal within the retinal pigment Food source: two types found in diet. epithelium. • Preformed vitamin A: animal products such as meat, fish, poultry and dairy foods. • Pro-vitamin A: plant-based foods such as fruits and vegetables. The most common type of provitamin A is beta-carotene. Vitamin A deficiency • the leading cause of preventable childhood blindness worldwide in developing countries • Prolonged and severe vitamin A deficiency can produce total and irreversible blindness. • ~250,000–500,000 children become blind each year (with the highest prevalence in Southeast Asia and Africa). (nyctalopia): Lack of vitamin • Night blindness A1 causes a decrease in retinal, which results in decreased production of rhodopsin; and a lower sensitivity of retina to light. Night blindness can occur in patients with GI absorption problem, e.g., celiac disease, cholestasis. Why? Br J Ophthalmol. 2006 Aug; 90(8): 955–956. http://medicaldictionary.thefreedictionary.com/vitamin+A+deficiency Guyton, Figure 51-5 Atropine dilates the pupil (mydriasis) and inhibits accommodation …by blocking parasympathetic effects; it is a competitive antagonist for muscarinic acetylcholine receptors, (increased heart rate, dry mouth, decreased sweating/lacrimation, blurry vision, vasodilation, confusion, hallucinations). Mnemonic: "hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter". • Atropine is extracted from the plant, nightshade (Atropa belladonna). • Belladonna (in Italian: bella=beautiful; donna=woman) • Used by Egyptians (Cleopatra), and throughout Europe (late 19th, early 20th century) to enhance beauty. Visual Pathways to the Cortex • • • • • Optic nerve - axons of ganglion cells of retina. Optic chiasm. – all fibers from nasal halves of retina cross to opposite side and join fibers from opposite temporal retina to form optic tracks. Synapse in dorsal lateral geniculate nucleus (LGN) of thalamus. From LGN to primary visual cortex by way of optic radiation. Two principle functions of LGN. – Relay information to primary visual cortex via optic radiation. – “Gate control” of information to primary visual cortex. (of thalamus) Figure 52-1 Organ of Corti • • • • • Receptor organ that generates nerve impulses. Contains rows of hair cells that have stereocilia. Hair cells are the receptor organs that generate APs in response to sound vibrations. The tectorial membrane lies above the stereocilia of the hair cells. Movement of the basilar membrane causes the stereocilia of the hair cells to shear back and forth against the tectorial membrane. Figure 53-7 The Tympanic Membrane and the Ossicular System • Tympanic membrane functions to transmit vibrations in the air to the cochlea (inner ear) • Amplifies the signal because the area of the tympanic membrane is 17 times larger than the oval window. • Tympanic membrane connected to the ossicles: malleus, incus, stapes Figure 53-1 Olfaction (aka, Smell) Because the tongue can only sense texture and differentiate between sweet, sour, bitter, salty, and umami, most of what is perceived as the sense of actually derived •taste Leastisunderstood of all from senses. •smell. Olfactory membrane located on the superior part of each nostril. • Olfaction involves CN I which are olfactory receptor neurons (ORNs). They are true neurons, which differentiates them from many other sensory system receptor types. Anosmia is the lack of smell • Can be due to traumatic injury, or from disruption to nasal epithelium or central pathways – Traumatic injury can sheer ORN axons in the cribriform plate – Infection (e.g. rhinitis) can block odorants and cause edema – Tumors (e.g. olfactory groove meningiomas) – Smoking decreases sensitivity to odorants – Associated with normal aging and neurodevelopmental disorders (e.g. Alzheimer’s and Parkinson diseases) • Most disruptions to “taste” are from olfactory issues, due to “flavor” being a perception that involves both senses • Constant regeneration of ORNs allows for many forms of anosmia to be temporary How does COVID-19 decrease taste and small? Why does COVID-19 affect smell and taste? While the precise cause of smell dysfunction is not entirely understood, the mostly likely cause is damage to the cells that support and assist the olfactory neurons, called sustentacular cells. These cells can regenerate from stem cells, which may explain why smell recovers quickly in most cases. How long does the loss of taste and smell last? Approximately 90% of those affected can expect improvement within four weeks. Unfortunately, some will Golgi Tendon Organ • • • • • • • low-threshold mechanoreceptors located in tendons increased muscle tension compresses nerve endings, opening stretch sensitive ion channels formed by branches of Type Ib afferents Autogenic inhibition reflex: a sudden relaxation of muscle at very high muscle tensions (protects against muscle tear) However, Golgi tendon organs signal muscle force through the entire physiological range, not only at high levels of tension. function is to equalize force among muscle fibers. only affects an individual muscle (adjacent muscles are not affected) Muscle spindles – detect both static and dynamic changes in muscle length – distributed throughout muscles – consist of intrafusal muscle fibers in parallel with extrafusal muscle fibers – density varies according to function • larger muscles with coarse movements have few (e.g., quadriceps) • smaller muscles with fine movements have many (e.g., extraocular muscles, muscles in hand and neck) Muscle spindles – detect both static and dynamic changes in muscle length – distributed throughout muscles – consist of intrafusal muscle fibers in parallel with extrafusal muscle fibers – density varies according to function • larger muscles with coarse movements have few (e.g., quadriceps) • smaller muscles with fine movements have many (e.g., extraocular muscles, muscles in hand and neck) Co-activation of alpha and gamma motor neurons Kandel, Schwartz and Jessell 4th edition 2000, McGraw Hill fig 36-9 co-activation prevents spindle from being unloaded during contraction; hence, proper damping function of spindle is maintained.