Flashcards in Medical Physiology Block 2 Week 1 Deck (62):
Describe the components of the Subdivisions of the Nervous system.
CNS: surrounded by meninges (dura, arachnoid, pia),brain and spinal cord, myelin producing oligodendrocytes, axons do not regenerate; PNS: lies outside the dura mater (ganglia, sensory receptors, peripheral portions of cranial nerves), Schwann cells produce myelin, axons can regenerate; ANS: part of CNS and PNS; control viscera (branchial origin or internal organ) (three divisions: sympathetic, parasympathetic, and enteric)
What are the four specialized regions in neurons?
cell body (soma: site of nucleus, ER, and Golgi), dendrites (branches; spines and infoldings increase surface area and allow localization of postsynaptic terminals to be closer to soma (better probability to induce an action potential), axon (begins at soma (hillock) and initial segment is the site where an action potential first arises (distal to hillock)), and presynaptic terminals
What is one way that neurons are similar to epithelial cells?
different populations of membrane proteins at each of the distinct domains of the neuronal plasma membrane (presynaptic terminal membrane proteins and dendritic membrane proteins have similar dichotomy to the membrane protein differences in basolateral and luminal surfaces of epithelial cells)
What structures are absent from an axon?
mRNA, ribosomes, and Golgi
Differentiate the features of axoplasmic transport: fast anterograde, fast retrograde, and slow anterograde
Fast anterograde: similar to movement of myosin on actin filaments in muscles (unidirectional; kinesin plays the role of myosin; carries vesicles and mitochondria); fast retrograde: dynein plays the role of myosin (mostly transports growth factors to soma); slow anterograde: g. The slowest moving proteins are neurofilament and microtubule subunits (0.2 to 1 mm/day) (component of the axonal transport mechanism; primarily utilized in response to nerve damage?)
What type of neuronal cell is characterized by the presence of dendritic spines? Which neuronal cell can be spiny or aspiny?
Pyramidal cells; stellate cells
What are the three ways that neurons can be classified?
axonal projection (projection neuron v interneuron (affects nearby neurons)); dendritic pattern (pyramidal v stellate (star-shaped); number of processes (unipolar, bipolar, multipolar)
Why is a dorsal root ganglion cell considered pseudo-polar?
sensory receptor sends action potential (through myelinated component) which bypasses the soma to innervate neurons (also through myelinated component) in the spinal cord
What is a considered to be a functional unit of the CNS?
neuron, glial cell, endothelial cell
What are pericytes?
neural stem cell (sit on capillaries) and secrete many growth factors to support the viability of the endothelial cell and neuron
What does afferent mean? efferent?
towards the CNS; away from the CNS
Describe neurulation. What induces it?
The first step in neurulation is formation of the neural plate at about the beginning of the third fetal week. Initially, the neural plate is only a single layer of neuroectoderm cells. Rapid proliferation of these cells, especially at the lateral margins, creates a neural groove bordered by neural folds. Continued cell division enlarges the neural folds, and they eventually fuse dorsally to form the neural tube. The neural tube is open at both ends, the anterior and posterior neuropores; notochord (mesodermal cells)
The lumen of the neural tube, the neural canal, develops into what?
four ventricles of the brain and the central canal of the spinal cord.
Neural crest cells give rise to cells for which subdivision of the nervous system?
What are the major divisions of the brain that have developed after the fourth gestastional week?
prosencephalon (forebrain), mesencephalon (midbrain); rombencephalon (hindbrain)
What are the major divisions of the brain that have developed after the fifth gestastional week?
prosencephalon gives rise to telencephalon (cerebral cortex; lumen = lateral ventricles) and diencephalon (lumen = third ventricle); mesencephalon (midbrain; lumen = cerebral aqueduct); the rhombencephalon can now be divided into the metencephalon (lumen = rostral fourth ventricle), which will give rise to the pons and cerebellum, and the myelencephalon (caudal fourth ventricle), which becomes the medulla
Describe development of the spinal cord.
As the neural tube thickens with cell proliferation, a groove called the sulcus limitans forms on the inner, lateral wall of the neural tube (The sulcus limitans divides the neural tube into a ventral area called the basal plate and a dorsal area called the alar plate (“wings”)); alar plate: produces dorsal horn (associative ;sensory); basal plate: produces intermediolateral column and ventral horn (motor)
Where is the origin of glial and neuronal cells?
neuroepithelial cells of the subventricular zone and ventricular zone (SVZ + VZ); PDGF and EGF influence these cells into dividing
What is unique to the ventricular zone when compared to the SVZ?
Produces progenitor cells (another cell of origin for neurons, glial cells, and ependymal cells)
Is the distribution (and number) of glial cells dependent on neurons?
Yes; determined by signals from nearby neurons or axons.
How do neurons move from the VZ (or SVZ) to the cortex?
move along radial glial cells; influenced by cell adhesion molecules (CAMs are calcium dependent), expression of ECM proteins laminin and fibronectin (secreted from cells) and integrins; chemical signals (chemotaxis)
How is apoptosis different from necrosis?
apoptosis: feature of neuronal pruning (initiates in the nucleus and requires protein synthesis); necrosis: Necrosis characterized by energy failure, loss of cell membrane integrity, and calcium entry (if mitochondria is dead and nucleus is intact, this suggests necrosis)
What is an astrocytic glial scar?
This scar is produced primarily by an enlargement of individual astrocytes, a process called hypertrophy, and increased expression of a particular cytoskeleton protein, glial acidic fibrillary protein
Can glial cells be replaced?
Yes; there is some evidence of neuronal replacement in adult brains (very uncommon)
What are the four lobes of the brain called? What are three segments of the brainstem called? What are the four segments of the spinal cord (vertebral column) called?
Frontal lobe, parietal lobe, temporal lobe, occipital lobe; midbrain, pons (relays signals from cortex to cerebellum), medulla; cervical (8), thoracic (12), lumbar (5), sacral (5) (coccyx or tailbone is the last vertebral column)
The spinal cord runs from the base of the skull to where?
first lumbar vertebra
Where is white matter in the spinal cord? Gray matter?
White matter outside of the spinal cord; gray matter, inside
What are three functions of the cerebellum?
balance (vestibular); regulates muscle tone; coordinates motor behavior via connections with cortex through thalamus
What is the difference between ganglia and nuclei?
Both are a cluster of neuronal cell bodies: ganglia = PNS; nuclei = CNS
Describe a peripheral nerve bundle.
Individual axons are surrounded by loose connective tissue called the endoneurium. Within the nerve, axons are bundled together in small groups called fascicles, each one covered by a connective tissue sheath known as the perineurium. The perineurium contributes structural stability to the nerve. Fascicles are grouped together and surrounded by a matrix of connective tissue called the epineurium. Fascicles within a nerve anastomose with neighboring fascicles. Axons shift from one fascicle to another along the length of the nerve, but they tend to remain in roughly the same general area within the nerve over long distances.
What is the path that a spinal nerve takes after leaving the CNS that innervates the upper extremity? lower extremity?
Brachial plexus; cauda equina (horse's tail)
Describe how ventricles are interconnected, where CSF is synthesized, secreted, circulated and drained in the brain
The two lateral ventricles each communicate with the third ventricle , which is located in the midline between the thalami, through the two interventricular foramina of Monro. The third ventricle communicates with the fourth ventricle by the cerebral aqueduct of Sylvius. CSF escapes from the fourth ventricle and flows into the subarachnoid space through three foramina: the two laterally placed foramina of Luschka and the midline opening in the roof of the fourth ventricle, called the foramen of Magendie; CSF is synthesized and secreted within the brain by a highly vascularized epithelial structure called the choroid plexus; Arachnoid granulations act as pressure-sensitive, one-way valves for bulk CSF clearance into the SSS; The pial-glial membrane has paracellular gaps through which substances can equilibrate between the subarachnoid space and BECF (same idea for ependymal cells surrounding ventricles)
Differentiate the composition of CSF from the plasma
CSF has lower concentrations of K + and amino acids than plasma does, and it contains almost no protein; Similar to plasma: osmolality, Na+, Ca2+, Cl-, HCO3-
Describe how CSF is synthesized and secreted into the ventricles
Choroid epithelial cells are cuboidal and have an apical (luminal) border with microvilli and cilia that project into the ventricle (i.e., into the CSF). The plexus receives its blood supply from the anterior and posterior choroidal arteries; The choroid epithelial cells are bound to one another by tight junctions that completely encircle each cell, an arrangement that makes the epithelium an effective barrier to free diffusion.
How is sodium secreted from the plasma into CSF?
The Na-K pump in the choroid plexus, unlike in other epithelia, is unusual in being located on the apical membrane, where it moves Na + out of the cell into the CSF—the first step. This active movement of Na + out of the cell generates an inward Na + gradient across the basolateral membrane, energizing basolateral Na + entry—the second step—through Na-H exchange and Na + -coupled HCO 3 − transport.
How is chloride secreted from the plasma into CSF?
The first step is the intracellular accumulation of Cl − by the basolateral Cl-HCO 3 exchanger. The second step is efflux of Cl − across the apical border into the CSF through either a Cl − channel or a K/Cl cotransporter.
The limiting factor for exchange of sodium at the basolateral membrane is intracellular hydrogen ion. Where does this intracellular hydrogen originate from?
carbonic anhydrase generates H+ and HCO 3−, from CO2 and H2O.
How is bicarbonate secreted from the plasma into CSF? Why is this important?
At the basolateral membrane, the epithelial cell takes up HCO 3 − through electroneutral Na/HCO 3 cotransporters and the Na + -driven Cl-HCO 3 exchanger (is already elevated in the epithelial cell as a result of carbonic anhydrase). Movement of bicarbonate at the apical membrane occurs through Na/HCO3 cotransporter and through chloride channels (permeable to bicarbonate); neutralizes acids produced in the CNS
How is potassium removed from the CSF?
The epithelial cell takes up K + by the Na-K pump and the Na/K/Cl cotransporter at the apical membrane. Most of the K + recycles back to the CSF, but a small amount exits across the basolateral membrane and enters the blood.
How are substances cleared from the brain?
Products of metabolism and other substances released by cells, perhaps for signaling purposes, can diffuse into the chemically stable CSF and ultimately be removed on a continuous basis either by bulk resorption into the venous sinuses or by active transport across the choroid plexus into the blood.
Describe the BBB and how it prevents blood constituents from entering the BECF
tight junctions prevent water-soluble ions and molecules from passing from the blood into the brain through the paracellular route (contain many mitochondria); thick basement membrane (basal lamina) underlies the endothelial cells and contains occasional pericytes (communicate with both endothelial and glial cell). Astrocytic endfeet (or processes) provide a nearly continuous covering of the capillaries and other blood vessels.
Know the major difference between the circumventricular organs (name them) and other organs/tissues in the brain
The capillaries of the brain are leaky in several areas: the area postrema, the posterior pituitary, the subfornical organ, the median eminence, the pineal gland, and the organum vasculosum laminae terminalis (OVLT) (surround the ventricles) In these regions, the neurons are directly exposed to the solutes of the blood plasma (lack BBB); The ependymal cells that overlie the leaky capillaries in some of these regions (e.g., the choroid plexus) are linked together by tight junctions that form a barrier between the local BECF and the CSF, which must be insulated from the variability of blood composition.
Know 3 different types of glial cells [astrocyte, oligodendrocyte, and microglia) in the brain and their functions
Astrocytes: provide lactate for neurons (store glycogen), regulate BECF by uptaking K+, regulate pH, characterized by gap junctions (syncytium), synthesize glutamine, secrete trophic factors, and endfeet regulate cerebral blood flow; oligodendrocytes myelinate axons, metabolize iron; microglia are macrophages of the brain (mesodermal origin, antigen-presenting (attract T cells)) (are normally inactive; when activated, proliferated and become phagocytic)
Describe how astrocytes regulate the [K+]o and help to stabilize the neuronal microenvironment
depolarization that is triggered by the increased extracellular [K + ] leads to the influx of HCO 3 − into astrocytes by the electrogenic Na/HCO 3 cotransporter; this influx of bicarbonate in turn causes a fall in extracellular pH that may diminish neuronal excitability; ii. Astrocytes can take up K + in response to elevated [K + ] o by three major mechanisms: the Na-K pump, the Na/K/Cl cotransporter, and the uptake of K + and Cl − through channels. Conversely, when neural activity decreases, K + and Cl − leave the astrocytes through ion channels (spatial buffering)
Describe glutamine-glutamate cycle that occurs between astrocytes and neurons
Glutamine is manufactured only in astrocytes by use of the astrocyte-specific enzyme glutamine synthetase to convert glutamate to glutamine (and GABA). Astrocytes release this glutamine into the BECF through the SNAT3 and 5 transporters for uptake by neurons through SNAT1 and 2. In the presynaptic terminals of neurons, glutaminase converts the glutamine to glutamate, for release into the synaptic cleft by the presynaptic terminal. Finally, astrocytes take up much of the synaptically released glutamate to complete this glutamate-glutamine cycle (glutamate clearance by an astrocyte from the synaptic cleft occurs by coupling the Na/K ATPase with a EAAT (excitatory amino acid transporter 1 or 2 (glutamate, hydrogen ion, 2 sodiums enter cell and a potassium molecule leaves the cell)).
What is the difference between anoxia and ischemia?
Ischemia prevents transport of both oxygen and glucose to the site of injury (anoxia only prevents oxygen)
Do the lateral ventricles communicate with each other?
Where is the choroid plexus complex in the four ventricles?
Lateral ventricles: inner radius of the inferior arm of lateral ventricles; roof of the third and fourth ventricle (inferior to cerebellum but superior to brainstem)
What is the glia limitans?
avascular astrocytic endfeet that abuts the pia from the brain side and is separated from the pia by a basement membrane. The pia adheres so tightly to the associated glia limitans in some areas that they seem to be continuous with each other; this combined structure is sometimes called the pial-glial membrane
Can objects move paracellularly through the arachnoid membrane?
Describe the dura mater.
The dura mater is a thick, inelastic membrane that forms an outer protective envelope around the brain. The dura has two layers that split to form the intracranial venous sinuses. Blood vessels in the dura mater are outside the blood-brain barrier
Is the rate of CSF production sensitive to ICP?
No; absorption greatly increases above 70 mm H20
If a patient has a tumor in the cerebral aqueduct of Sylvius, you would expect enlarged ventricles in which region(s)?
Both lateral ventricles and third ventricle
What is Acetazolamide?
blocks carbonic anhydrase and slows CSF production
What can readily pass the BBB?
Uncharged and lipid soluble molecules readily pass the BBB (and water); aquaporins allow single water molecules through (ions are too large due to the hydration cell surround them)
What is the resting potential of astrocytes? What channel is responsible for this?
Astrocytes resting membrane potential is about -85 mV (close to reversal potential of potassium suggest relative potassium conductance is greater than in neurons (inward rectifying potassium channels are important in setting resting potential of astrocytes)
What protein is found in myelin from oligodendrocytes? Schwann cells?
Oligo: myelin basic protein and proteolipic protein; Schwann cells: protein zero
How does glucose cross the BBB?
Glucose exits endothelial cells (through the BBB) via the Glut1 transporter (on both sides of endothelial cells; also found in astrocytes; neuron uses Glut3 transporter)
How much CSF is produced per day?
Total CSF: 500 ml/day (30 mL in the ventricles and 120 mL in the subarachnoid spaces of the brain and spinal cord is turned over 3 times a day)
Why is CSF absorbed by arachnoid granulations (or villi)?
Net CSF movement into venous blood is promoted by the pressure of the CSF, which is higher than that of the venous blood. When intracranial pressure (equivalent to CSF pressure) exceeds ∼70 mm H 2 O, absorption commences and increases with intracranial pressure
What are the two type of astrocytes?
Fibrous astrocytes (found mainly in white matter) have long, thin, and well-defined processes; protoplasmic astrocytes (found mainly in gray matter) have shorter, frilly processes