Urinary Concentration – The Medullary Osmotic Gradient

June 22, 2016 Anatomy, Critical Care, Hemodynamics, Histology, Nephrology, Physiology and Pathophysiology No comments , , , , , , , , , , , , , ,

The kidneys can produce a range of urine osmolalities depending on the levels of ADH. The production of hypo-osmotic urine is an understandable process: The tubules (particularly the thick ascending limb of Henle's loop) reabsorb relatively more solute than water, and the dilute fluid that remains in the lumen is excreted. The production of hyperosmotic urine is also straightfoward in that reabsorption of water from the lumen into a hyperosmotic interstitium concentrates that luminal fluid, leaving concentrated urine to be excreted.

The Mechanism to Generate Medullary Osmotic Gradient

There is a gradient of osmolality (hyperosmotic), increasing from a nearly iso-osmotic value at the corticomedullary border to a maximum of greater than 1000 mOsm/kg at the papilla. The peak osmolality is variable depending on dehydration or overhydration, where highest during periods of dehydration and lowest (approximately half of that during excess hydration) during excess hydration.

In the steady state there must be mass balance, that is, every substance that enters the medulla via tubule or blood vessel must leave the medulla via tubule or blood vessels. However, during development of the gradient there are transient accumulations of solute, and during washout of the gradient there are losses. To develop the osmotic gradient in the medullary interstitium, there must be deposition of solute in excess of water. It is reabsorption of sodium and chloride by the thick ascending limb in excess of water reabsorbed in the thin descending limbs that accomplishes this task. At the junction between the inner and outer medulla, the ascending limbs of all loops of Henle, whether long or short, turn into thick regions and remain thick all the way back until they reach the original Bowman's capsules. As they reabsorb solute without water and dilute the luminal fluid, they simultaneously add solute without water to the surrounding interstitium. This action of the thick ascending limb is absolutely essential and is the key to everything else that happens. If transport in the thick ascending limb is innhibited, the lumen is not diluted and the interstitium is not concentrated, and the urine becomes iso-osmotic.


  • For thick ascending limbs in the cortex, reabsorbed solute is taken up by abundant cortex blood flow so intersititum osmolality in the cortex approximately equal plasma
  • High concentratiion sodium level in outer medulla interstitium makes them diffuse into DVR and AVR
  • Hyperosmotic sodium in AVR can diffuse into nearby DVR – the countercurrent exchange

For those portions of the thick ascending limbs in the cortex, the reabsorbed solute simply mixes with material reabsorbed by the nearby proximal convoluted tubules. Because the cortex contains abundant peritubular capillaries and a hight blood flow, the reabsorbed material immediately moves into the vasculature and returns to the general circulation. However, in the medulla, the vascular anatomy is arranged differently and total blood flow is much lower. Solute that is reabsorbed and deposited in the outer medullary interstitium during the establishment of the osmotic gradient is not immediately removed, that is, it accumulates. The degree of accumulation before a steady state is reached is a function of the arrangement of the vasa recta, their permeability properties and the volume of blood flowing within them.

Imagine first a hypothetical situation of no blood flow. Sodium would accumulate in the outer medulla without limit, because there would be no way to remove it. But, of course the outer medulla is perfused with blood, as are all tissues. Blood enters and leaves the outer medulla through parallel bundles of descending and ascending vasa recta (DVR and AVR). These vessels are permeable to sodium. Therefore sodium enters the vasa recta driven by the rise in concentration in the surrounding interstitium. Sodium entering the ascending vessels returns to the general circulation, but sodium in the descending vessels is distributed deeper into the medulla, where it diffuses out across the endothelia of the vassa recta and the interbundle capillaries that they feed, thereby raising the sodim content throughout the medulla.

Later, the interbundle capillaries drain into ascending vasa recta that lie near descending vasa recta. The walls of the ascending vasa recta are fenestrated, allowing movment of water and small solutes between plasma and interstitium. As the sodium concentration of the medullary interstitium rises, blood in the ascending vessels also takes on an increasingly higher sodium concentration. However, blood entering the medulla always has a normal sodium concentration (approximtely 140 mEq/L). Accordingly, some of the sodium begins to re-circulate, diffusing out of ascending vessels and reentering nearbydescending vessels that contain less sodium (countercurrent exchange). So sodium is entering descending vasa recta from 2 sources – re-circulated sodium from the ascending vasa recta, and new sodium from the thick ascending limbs. Over time, everything reaches a steady state in which the amount of new sodium entering the interstitium from thick ascending limbs matches the amount of sodium leaving the interstitium in ascending vasa recta. At its peak, the concentration of sodium in the medulla may reach 300 mEq/L, more than double its value in the general circulation. Since sodium is accompanied by an anion, mostly chloride, the contribution of salt to the medullary osmolality is approximately 600 mOsm/kg.


  • While solute can accumulate without a major effect on renal volume, the amount of water in the medullary interstitium must remain nearly constant; otherwise the medulla would undergo significiant swelling or shrinking.
  • Because water is always being reabsorbed from the medullary tubules into the interstitium (from descending thin limbs and medullary colelcting ducts), that water movement must be matched by equal water movement from the interstitium to the vasculature.
  • Blood entering the medulla has passed through glomeruli, thereby concentrating the plasma proteins. While the overall osmotic content (osmolality) of this blood is essentially isosmotic with systemic plasma, its oncotic pressure is considerably higher.

The challenge for the kidneys is to prevent dilution of the hyperosmotic interstitium by water reabsorbed from the tubules and by water diffusing out of the iso-osmotic blood entering the medulla. The endotheial cells of descending vasa recta contain aquaporins. So water is drawn osmotically into the outer medullary interstitium by the high salt content in a manner similar to water being drawn out of tubular elements. At first glance it seems that this allows the undesired diluting effect to actually take place. But, of course, solute is also constantly being added from the nearby thick ascending limbs. The loss of water from descending vasa recta in the outer medulla serves the useful purpose of raising the osmolality of blood penetrating the inner medulla and decreasing its volume, thereby reducing the tendency to dilute the inner medullary interstitium. The ascending vasa recta have a fenestrated endothelium, allowing free movement of water and small solutes. Since the oncotic pressure is high, water entering the interstitium of the outer medulla from descending vasa recta is taken up by ascending vasa recta and removed from the medulla. In addition, water reabsorbed from tubular elements (descending thin limbs and collecting ducts) is also taken up by ascending vasa recta and removed, thereby preserving constancy of total medullary water content.

The magnitude of blood flow in the vasa recta is a crucial variable. The peak osmolality in the interstitium depends on the ratio of sodium pumping by the thick ascending limbs to blood flow in the vasa recta. If this ratio is high (meaning low blood flow), water from the isosmotic plasma entering the medulla in descending vasa recta does not dilute the hyperosmotic interstitium. In effect the "salt wins" and osmolality remains at a maximum. But in conditions of water excess, this ratio is very low (high blood flow) and the diluting effect of water diffusing out of descending vasa recta is considerable. In part the tendency to diulte is controlled by ADH (due to its vasoconstriction effect to limit the blood flow of DVR).


The peak osmolality in the renal papilla reaches over 1000 mOsm/kg. Approximately half of this is accounted for by sodium and chloride, and most of the rest is (500-600 mOsm/kg) accounted for by urea. Urea is a very special substance for the kidney. It is an end product of protein metabolism, waste to be excreted, and also an important component for the regulation of water excretion. For the handle of urea in the kidneys: 

1.There are no membrane transport mechanisms in the proximal tubule; instead, it easily permeates the tight junctions of the proximal tubule where it is reabsorbed paracellularly.

2.Tubular elements beyond the proximal tubule express urea transporters and handle urea in a complex, regulated manner.

The gist of the renal handling of urea is the following: it is freely filtered. About half is reabsorbed passively in the proximal tubule. Then an amount equal to that reabsorbed is secreted back into the loop of Henle. Finally, about half is reabsorbed a second time in the medullary collecting duct. The net result is that about half the filtered load is excreted.

Urea does not permeate lipid layer because of its highly polar nature, but a set of uniporters transport urea in various places beyond the proximal tubule and in other sites within the body. Because urea is freely filtered, the filtrate contains urea at a concentration identical to that in plasma. In the proximal tubule when water is reabsorbed, the urea concentation rises well above the plasma urea concentration, driving diffusion through the leaky tight junctions. Roughly, half the filtered load is reabsorbed in the proximal tubule by the by the paracellular route. As the tubular fluid enters the loop of Henle, about half the filtered urea remains, but the urea concentration has increased somewhat above its level in the filtrate because proportionally, more water than urea was reabsorbed. At this point, the process becomes fairly complicated.

The interstitium of the medulla has a considerably higher urea concentration than does plasma. The concentration increases from the outer to the inner medulla. Since the medullary interstitial urea concentration is greater than that in the tubular fluid entering the loop of Henle, there is a concentration gradient favoring secretion into the lumen. The tight junctions in the loop of Henle are no longer permeable, but the epithelial membranes of the thin regions of the Henle's loops express urea uniporters, members of the UT family. This permits secretion of urea into the tubule. In fact, the urea secreted from the medullary interstitium into the thin regions of the loop of Henle replaces the urea previously reabsorbed in the proximal tubule. Thus, when tubular fluid enters the thick ascending limb, the amount of urea in the lumen is at least as large as the filtered load. However, because about 80% of the filtered water has now been reabsorbed, the luminal urea concentration is now several times greater than in the plasma. Beginning with the thick ascending limb and continuing all the way to the inner medullary collecting ducts (through the distal tubule and cortical collecting ducts), the apical membrane urea permeability (and the tight junction permeability) is essentially zero. Therefore, an amount of urea roughly equal to the filtered load remains within the tubular lumen and flows from the cortical into the medullary collecting ducts.

During the transit through the cortical collecting ducts variable amounts of water are reabsorbed, significantly concentrating the urea.We indicated eariler that the urea concentration in the medullary interstitium is much greater than in plasma, but the luminal concentration in the medullary collecting ducts is even higher (up to 50 times its plasma value), so in the inner medulla the gradient now favors reabsorption and urea is reabsorbed a second time via another isoform of UT urea uniporter. It is this urea reabsorbed in the inner medulla that leads to the high medullary interstitial concentration, driving urea secretion into the thin regions of the loop of Henle.

[Histology] Basic Four Types of Tissues – Connective Tissues

May 23, 2016 Anatomy, Histology No comments , , , , , , , , , , , , , , , , ,

The different types of connective tissue maintain the form of organs throughout the body. Differences in composition and amount of the cells, fibers, and ground substance make up variety of connective tissue types. Connective tissues provide a matrix that supports and physically connects other tissues and cells together in organs. The interstitial fluid of connective tissue gives metabolic support to cells as the medium for diffusion of nutrients and waste products. Unlike other tissue types, which consist mainly of cells, the major constituent of connective tissue is the extracellular matrix/ECM, which consists of different combinations of protein fibers (e.g., collagens and elastic fibers) and ground substance (a complex of anionic, hydrophilic proteoglycans, glycosaminoglycans/GAGs, and multiadhesive glycoproteins). The hydrated nature of connective tissue ground substance provides the medium for the exchange of nutrients and metabolic wastes between cells and the blood supply.


Fibroblasts and certain other cells are typically present in connective tissue proper. Fibroblasts originate locally from mesenchymal cells and are permanent residents of connective tissue; other cells found here, such as macrophages, plasma cells, and mast cells, originate from hematopoietic stem cells in bone marrow, circulate in the blood, and then move into connective tissue where they function. Leukocytes are transient cells of most connective tissues; they also originate in the bone marrow and move to the connective tissue where they function for a few days, the die by apoptosis.


Fibroblasts, the most common cells in connective tissue, produce and maintain most of the tissue's extracellular components. Fibroblasts synthesize and secrete collagen (the most abundant protein of the body) and elastin, which form large fibers, as well as the GAGs, proteoglycans, and multiadhesive glycoproteins that comprise the ground substance. After being secreted, most of the ECM components undergo further modification outside the cell before assembling as a matrix.

Two levels of fibroblast activity can be observed histologically. Cells with intense synthetic activity are morphologically distinct from the quiescent fibroblasts that are scattered within the matrix they have already synthesized.

Fibroblasts are targets of many families of proteins called growth factors that influence cell growth and differentiation. In adults, connective tissue fibroblasts rarely undergo division. However, stimulated by locally released growth factors, cell cycling and mitotic activity resume when the tissue requires additional fibroblasts.


Adipocytes are found in connective tissue of many organs. These cells are specialized for cytoplasmic storage of lipid as neutral fats, or less commonly for the production of heat.


Macrophages are characterized by their well-developed phagocytic ability and specialize in turnover of protein fibers and removal of dead cells, tissue debris, or other particulate material. Macrophages play an important role in the early stages of repair after tissue damage, and under such conditions of inflammation these cells accumulate in connective tissue by local proliferation of macrophages in addition to monocyte recruitment from the blood. In addition to debris removal, these cells are highly important for the uptake, processing, and presentation of antigens for lymphocyte activation.

They derive from bone marrow precursor cells that divide, producing monocytes that circulate in the blood. These monocytes cross the epithelial wall of venules to penetrate connective tissue, where they differentiate further, mature, and acquire the morphologic features of phagocytic cells. Therefore, monocytes and macrophages are the same cell at different stages of maturation.

The macrophage-like cells have been given different names in different organs, for example, Kupffer cells in the liver, microglial cells in the central nervous system, Langerhans cells in the skin, and osteoclasts in bone tissue. However, all are derived from monocytes and all are long-living cells and may survive for months in the tissues.

Mast cells

The cytoplasm of mast cells is filled with basophilic secretory granules many of which have the bioactive role in the local inflammatory response. A partial list of important molecules released from the secretory granules include:

  • Heparin
  • Histamine
  • Serine proteases
  • Eosinophil and neutrophil chemotactic factors
  • Cytokines
  • Phospholipid

Occurring in connective tissue of many organs, mast cells are especially numerous near small blood vessels in skin and mesenteries (perivascular mast cells) and in the tissue that lines digestive and respiratory tracts (mucosal mast cells); the granule content of the two populations di ers some what. These major locations suggest that mast cells place themselves strategically to function as sentinels detecting invasion by microorganisms.

Plasma cells

Plasma cells are B-lymphocyte-derived, antibody-producing cells. There are at least a few plasma cells in most connective tissues. Their average lifespan is only 10-20 days.


Besides macrophages and plasma cells, connective tissue normally contains other leukocytes derived from cells circulating in the blood. Leukocytes make up a population of wandering cells in connective tissue. They leave blood by migrating between the endothelial cells lining venules to enter connective tissue by a process called diapedesis. Most leukocytes function for a few hours or days in connective tissue and then die. However, some lymphocytes normally leave the interstitial fluid of connective tissue, enter blood or lymph, and move to selected lymphoid organs.


The fibrous components of connective tissue are elongated structures formed from protein that polymerize after secretion from fibroblasts. The three main types of fibers include collagen, reticular, and elastic fibers. Collagen and reticular fibers are both formed by proteins of the colagen family, and elastic fibers are composed mainly of the protein elastin. These fibers are distributed unequally among the different types of connective tissue, with the predominant fiber type usually responsible for conferring specific tissue properties.


The collagens constitute a family of proteins selected during evolution for their ability to form a variety of extracellular structures. The various fibers, sheets, and networks made of collagens are all extremely strong and resistant to normal shearing and tearing forces. Collagen is a key element of all connective tissues, as well as epithelial basement membranes and the external laminae of muscle and nerve cells.

Collagen is the most abundant protein in the human body, representing 30% of its dry weight. An unusually large number of posttranslational processing steps are required to prepare collagen for its final assembly in the ECM. They are many types of collagen and we will take a look at them in future.

Reticular fibers

Found in delicate connective tissue of many organs, reticular fibers consist mainly of collagen type III. This collagen forms an extensive network (reticulum) of extremely thin, heavily glycosylated fibers. Reticular fibers produced by fibroblasts occur in the reticular lamina of basement membranes and typically also surround adipocytes, smooth muscle and nerve fibers, and small blood vessels. Delicate reticular networks serve as the supportive stroma for the parenchymal secretory cells and rich microvasculature of the liver and endocrine glands. Abundant reticular fibers also characterize the stroma of hemopoietic tissue (bone marrow) and some lymphoid organs (eg, spleen and lymph nodes) where they support rapidly changing populations of proliferating cells and phagocytic cells.

Elastic fibers

Elastic fibers form sparse networks interspersed with collagen bundles in many organs,  particularly those subject to much bending or stretching. Elastic fibers have physical properties similar to those of rubber, allowing tissues to be stretched or distended and return to their original shape. Elastic fibers are a composite of fibrillin microfibrils embedded in a larger mass of cross-linked elastin.

Ground Substance

The ground substance of the ECM is a highly hydrated (with much bound water), transparent, complex mixture of macromolecules, principally of three classes: glycosaminoglycans/GAGs, proteoglycans, and multiadhesive glycoproteins. It fills the space between cells and fibers in connective tissue and, because it is viscous, acts as both a lubricant and a barrier to the penetration of invaders. GAGs bind large amounts of water, which causes the polyaminos to swell and occupy a large space in the tissue.

Types of Conenctive Tissue

Screen Shot 2016-05-23 at 10.43.00 PMLoose connective tissue is very common and generally supports epithelial tissue. It comprises a thick layer (lamina propria) beneath the epithelial lining of the digestive system and fills the spaces between muscle and nerve fibers. Usually well-vascularized whatever their location, thin layers of loose connective tissue surround most small blood vessels of the body. Also called areolar tissue, the loose connective tissue typically contain cells, fibers, and ground substance in roughly equal parts. The most numerous cells are fibroblasts, but the other types of connective tissue cells are also present, along with nerves and blood vessels. Collagen fibers predominate, but elastic and reticular fibers are also present. With a moderate amount of ground substance, loose connective tissue has a delicate consistency; it is flexible and not very resistant to stress.

Dense connective tissue is adapted to offer stress resistance and protection. It has the same components found in loose connective tissue, but with fewer cells and a clear predominance of collagen fibers over ground substance. Dense connective tissue is less flexible and far more resistant to stress than loose connective tissue. In dense irregular connective tissue bundles of collagen fibers appear randomly interwoven, with no definite orientation. The collagen fibers form a tough three-dimensional network, providing resistance to stress form all directions. Dense irregular connective tissue is often found closely associated with loose connective tissue, with the two types frequently grading into each other and making distinctions between them somewhat arbitrary. Collagen bundles of dense regular connective tissue are arranged according to a definite pattern, with fibers and fibroblasts aligned in parallel for resistance to prolonged or repeated stresses exerted in the same direction.

In reticular tissue fibers of type III collagen form a delicate 3D network that supports various types of cells. The fibrous network of this specialized connective tissue is produced by modified fibroblasts called reticular cells that remain associated with and partially covering the fibers. The loose disposition of glycosylated reticular fibers provides a framework with specialized microenvironments for cells in hemopoietic tissue and some lymphoid organs (bone marrow, lymph nodes, and spleen). The resulting cell-lined system creates a meshwork for the passage of lymphocytes and lymph. Macrophages and other cells of the mononuclear phagocyte system are also dispersed within these reticular tissues to monitor cells formed there or passing through and to remove debris.

[Anatomy] Motor Pathways

April 30, 2016 Anatomy, Neurology No comments , , , , , , , , , ,

Screen Shot 2016-04-30 at 3.31.56 PMSomatosensory Pathways

Motor pathways are formed from the cerebral nuclei, the cerebllum, descending projection tracts, and motor neurons. Descending project tracts are motor pathways that originate from the cerebral cortex and brainstem. There are at least two motor neurons in the somatic motor pathway: an upper motor neuron and a lower motor neuron. Motor neurons within these tracts either synapse directly on motor neurons in the CNS or on interneurons that, in turn, synapse on motor neurons. The cell body of an upper motor neuron is housed within either the cerebral cortex or a nucleus within the brainstem. Axons of the upper motor neuron synapse either directly on lower motor neurons or on interneurons that synapse directly on lower motor neurons. The cell body of a lower motor neuron is housed either within the anterior horn of the spinal cord or within a brainstem cranial nerve nucleus. Axon of the lower motor neurons exit the CNS and project to the skeletal muscle to be innervated.

Motor neuron axons form two types of somatic motor pathways: direct pathways and indirect pathways. The direct pathways are responsible for conscious control of skeletal muscle muscle activity, and the indirect pathways are responsible for unconscious control of skeletal muscle activity.

Direct Pathway

The direct pathway originates in the pyramidal cells of the primary motor cortex. Their axons project either into the brainstem or into the spinal cord to synapse directly on lower motor neurons. The axons from pyramidal cell upper motor neurons descend through the internal capsule, enter the cerebral peduncles, and ultimately form two descending motor tracts of the direct pathway: corticobulbar tracts and corticospinal tracts.

Corticobulbar Tracts (upper motor neurons + lower motor neurons)

The corticobulbar tracts originate from the facial region of the motor homunculus within the primary motor cortex. Axons of these upper motor neurons extend to the brainstem, where they synapse with lower motor neuron cell bodies that are housed within brainstem cranial nerve nuclei. Axons of these lower motor neurons help form the cranial nerves. The corticobulbar tracts transmit motor information to control the following movements:

  • Eye movement (via CN III, IV, and VI)
  • Cranial, facial, pharyngeal, and laryngeal muscles (via CN V, VII, IX, and X)
  • Some superficial muscles of the back and neck (via CN XI)
  • Intrinsic and extrinsic tongue muscles (via CN XII)

Corticospinal Tracts (upper motor neurons + lower motor neurons)

Screen Shot 2016-04-30 at 3.34.15 PMThe corticospinal tracts descend from the cerebral cortex through the brainstem and form a pair of thick anterior bulges in the medulla oblongata called the pyramids. Then they continue into the spinal cord to synapse on lower motor neurons in the anterior horn of the spinal cord. The corticospinal tracts are composed of two components: lateral and anterior corticospinal tracts. The lateral corticospinal tracts include about 85% of the axons of the upper motor neurons that extend through the medulla oblongata. They decussate within the pyramids of the medulla oblongata and then form the lateral corticospinal tracts in the lateral funiculi of the spinal cord. These tracts contain axons that innervate both lower motor neurons of the anterior horn of the spinal cord and interneurons within the spinal cord. Axons of the lower motor neurons innervate skeletal muscles that control skilled movement in the limbs. The anterior corticospinal tracts represent the remaining 15% of the axons of upper motor neurons that extend through the medulla oblongata. The axons of these neurons do not decussate at the level of the medulla oblongata. Instead, they remain on their original side of the CNS and descend ipsilaterally, meaning "on the same side", to form the anterior corticospinal tracts in both anterior white funiculi. At each spinal cord segment, some of these axons decussate through the median plane in the anterior white commissure. After crossing to the opposite side, they synapse either with interneurons or lower motor neurons in the anterior horn of the spinal cord. Axons of the lower motor neurons innervate axial skeletal muscle.


Indirect Pathway

Several nuclei within the midbrain initiate motor commands for activities that occur at unconscious level. These nuclei and their associated tracts constitute the indirect pathway, so named because upper motor neurons originate within brainstem nuclei (that is, they are not pyramidal cells in the cerebral cortex). The axons of the indirect pathway take a complex, circuitous route before finally conducting the motor impulse into the spinal cord. Motor impulses conducted by axons of the motor, sensory, and association cortical areas, as well as input from the limbic system. Most of the output from cerebral nuclei goes to the primary motor cortex; cerebral nuclei do not exert direct control over lower motor neurons. Cerebral nuclei provide the patterned background movements needed for conscious motor activities by adjusting the motor cammands issued in other nuclei.

Role of the Cerebellum

The cerebellum plays a key role in movement by regulating the functions of the motor pathways. The cerebellum continously receives convergent input from the various sensory pathways and from the motor pathways themselves. In this way, the cerebellum unconsciously perceives the state of the body, receives the plan for movement, and then follows the activity to see if it was carried out correctly. When the cerebellum detects a disparity between the intended and actual movement, it may generate an error-correting signals. This singal is transmitted to both the premotor and primary motor cortices via the thalamus and the brainstem. Descending pathways then transmit these error-correting signals to the motor neurons. Thus, the cerebellum influences and controls movement by indirectly affecting the excitability of motor neurons.


Corticospinal tract


April 22, 2016 Anatomy, Neurology, Physiology and Pathophysiology No comments , , , , , , , , , , , ,

Reflex are rapid, automatic, involuntary reactions of muscles (cardiac, smooth, and skeleton) or glands to a stimulus. All reflexes have similar properties:

  • A stimulus is required to initiate a response to sensory input.
  • A rapid response requires that few neurons be involved and synaptic delay be minimal.
  • A preprogrammed response occurs the same way every time.
  • An involuntary response requires no intent or pre-awareness of the reflex activity. Thus, reflexes are usually not suppressed. Awareness of the stimulus occurs after the reflex action has been completed, in time to correct or avoid a potentially dangerous situation.

An example of a reflex occurs when you accidentally touch a hot burner on a stove. Instantly and automatically, you remove your hand from the stimulus, even before you are completely aware that your hand was touching something extremely hot. A reflex is a survival mechanism; it allows us to quickly respond to a stimulus that may be dtrimental to our well-being without having to wait for the brain to process the information.

Components of a Reflex Arc

A reflex arc is the neural "wiring" of a single reflex. It always begins at a receptor in the PNS, communicates with the CNS, and ends at a peripheral effector, such as a muscle or gland cell. The number of intermediate steps varies, depending on the complexity of the reflex. Generally, five steps are involved in a simple reflex arc, including:

  • Stimulus activates receptor. Sensory receptors (dendritic endings of a sensory of a sensory neuron) respond to both external and internal stimuli, such as temperature, pressure, or tactile changes.
  • Nerve impulse travels through sensory neuron to the CNS. Sensory neurons conduct impulses from the receptor into the spinal cord.
  • Information from nerve impulse is processed in the integration center by interneurons. More complex reflexes may use a number of interneurons within the CNS to integrate and process incoming sensory information and transmit information to a motor neuron. Sensory information is also sent to the brain through interneuron collaterals. The simplest reflexes do not involve interneurons; rather, the sensory neuron synapses directly on a motor neuron in the anterior gray horn of the spinal cord.
  • Motor neuron transmits nerve impulse to effector. An effector is a peripheral target organ that responds to the impulse from the motor neuron. The motor neuron transmits a nerve impulse through the anterior root and spinal nerve to the peripheral effector organ.
  • Effector responds to nerve impulse from motor neuron. The effector response is intended to counteract or remove the original stimulus.

Reflex arcs may be ipsilateral or contralateral. A relfex arc is termed ipsilateral when both the receptor and effector organs of the reflex are on the same side of the spinal cord. A reflex arc is contralateral when the sensory impulses from a receptor organ cross  over through the spinal cord to activate effector organs in the opposite limb.

Reflexes also may be monosynaptic or polysynaptic. A monosynaptic reflex is the simplest of all reflexes. The sensory axons synapse directly on the motor neurons, whose axons project to the effector. Interneurons are not involved in processing this reflex. Very minor synaptic delay is incurred in the single synapse of this reflex arc, resulting in a very prompt reflex response. Polysynaptic reflexes have more complex neural pathways that exhibit a number of synapses involving interneurons within the reflex arc. Because this reflex arc has more components, there is a more prolonged delay between stimulus and response.

Autonomic Reflexes

The autonomic nervous system helps maintain homestasis through the involuntary activity of autonomic reflexes, also termed visceral reflexes. Autonomic reflexes consist of smooth muscle contractions, cardiac muscle contractions, or secretion by glands that are mediated by autonomic reflex arcs in response to a specific stimulus. A classic autonomic reflex involves the reduction of blood pressure. When an individual has elevated blood pressure, streth receptors in the walls of large blood pressures are stimulated. Impulses from these stretch receptors then travel through visceral sensory neurons to the cardiac center in the medulla oblongata. This leads to parasympathetic input to the pacemaker of the heart, resulting in a decrease in heart rate and a concomitant decrease in blood pressure. Autonomic reflexes are comparable to spinal reflexes because they involve a sensory receptor, sensory neurons, interneurons in the CNS, motor neurons, and effector cells.

[Anatomy] Sensory Pathways

April 16, 2016 Anatomy, Neurology No comments , , , , , , , , , , , , , , , , , , ,

The CNS communicates with peripheral body structrues through pathways. These pathways conduct either sensory or motor information; proccessing and integration occur continuously along them. These pathways travel through the white matter of the brainstem and/or spinal cord as they connect various CNS regions with cranial and spinal nerves. A pathway consists of a tract and nucleus. Tracts are groups or bundles of axons that travel together in the CNS. A nucleus is a collection of neuron cell bodies located within the CNS. Nervous system pathways are sensory or motor. Sensory pathways are also called ascending pathways because the sensory information gathered by sensory receptors ascends through the spinal cord to the brain, whereas motor pathways are also called descending pathways because they transmit motor information that descends from the brain through the spinal cord to muscles or glands. Most of the nervous system pathways we discuss in this thread share several general characteristics:

  • Most pathways decussate from one side of the body to the other side at some point in their travels. This decussation means that the left side of the brain processes information from the right side of the body, and vice versa.
  • In most pathways, there is a precise correspondence of receptors in body regions, through axons, to specific functional areas in the cerebral cortex (ascending pathways), and vice versa for descending pathways. This correspondence is called somatotopy.
  • All pathways are composed of paired tracts. A pathway on the left side of the CNS has a matching tract on the right side of the CNS. Because each tract innervates structures on only one side of the body, both left and right tracts are needed to innervate both the left and right sides of the body.
  • Most pathways are composed of a series of two or three neurons that work together. Sensory pathways have primary neurons, secondary neurons, and sometimes tertiary neurons that facilitate the pathway's functioning. In contrast, motor pathways use an upper motor neuron and a lower motor neuron. The cell bodies are located in the nuclei associated with each pathway.

Screen Shot 2016-04-29 at 9.37.43 PMSensory Pathways

Sensory pathways are ascending pathways that conduct information about limb position and the sensations of touch, temperature, pressure, and pain to the brain. Somatosensory pathways process stimuli received from receptors within the skin, muscles, and joints, whereas viscerosensory pathways process stimuli received from the viscera.

Somatosensory Pathways

The multiple types of body sensations detected by the somatosensory system are grouped into three spinal cord pathways, each with a different brain destination: 1.Discriminative touch permits us to describe textures and shapes of unseen objects and includes pressure, touch, and vibration perception; 2.Temperature and pain allow us to detect those sensations, as well as the sensation of an itch; 3.Proprioception allows us to detect the position of joints, stretch in muscles, and tension in tendons. Sensory receptors detect stimuli and then conduct nerve impulses to the central nervous system. Sensory pathway centers within either the spinal cord or the brainstem process and filter the incoming sensory information. These centers determine whether the incoming sensory stimulus should be transmitted to the cerebrum or terminated. Consequently, not all incoming impulses reach the cerebral cortex and our conscious awareness.

Posterior Funiculus – Medial Lemniscal Pathway

Screen Shot 2016-04-30 at 1.49.56 PMThis pathway projects through the spinal cord, brainstem, and diencephalon before terminating within the cerebral cortex. Its name derives from two components: the tracts within the spinal cord, collectively called the posterior funiculus; and the tracts within the brainstem, collectively called the medial lemniscus. This pathway conducts sensory stimuli concerned with proprioceptive information about limb position and discriminative touch, precise pressure, and vibration sensations.

The posterior funiculus – medial lemniscal pathway uses a chain of three neurons to singal the brain about a specific stimulus. Axons of the primary neurons traveling in spinal nerves reach the CNS through the posterior roots of spinal nerves. Upon entering the spinal cord, these axons ascend within a specific posterior funiculus, either the fascinculus cuneatus or the fasciculus gracilis. The fasciculus cuneatus houses axons from sensory neurons originating in the upper limbs, superior trunk, neck, and posterior region of the head, whereas the fasciculus gracilis carries axons from sensory neurons originating in the lower limbs and inferior trunk. The senory input into both posterior funiculi is organized somatotopically – that is, there is a correspondence between a receptor's location in a body part and a particular location in the CNS. Thus, the sensory information originating from inferior regions is medially located within the fasciculus, and the sensory information originating at progressively more superior regions is located more laterally.

Sensory axons ascending within the posterior funiculi synapse on secondary neuron cell bodies housed within a posterior funiculus nucleus in the medulla oblongata. These nuclei are either the nucleus cuneatus or the nucleus gracilis, and they correspond to the fasciculus cuneatus and fasciculus gracilis, respectively. These secondary neurons then project axons to relay the incoming sensory information to the thalamus on the oposite side of the brain through medial lemniscus. Decussation occurs after secondary neuron axons exit their specific nuclei and before they enter the medial lemniscus. As the sensory information travels toward the thalamus, the same classes of sensory input (touch, pressure, and vibration) that have been collected by cranial nerves CN V (trigeminal), CN VII (facial), CN IX (glossopharyngeal), and CN X (vagus) are integrated and incorporated into the ascending pathways, collectively called the trigeminothalamic tract.

The axons of the secondary neurons synapse on cell bodies of the tertiary neurons within the thalamus. Within the thalamus, the ascending sensory information is sorted according to the region of the body involved (somatotopically). Axons from these tertiary neurons conduct sensory information to a specific location of the primary somatosensory cortex.

Anterolateral Pathway

Screen Shot 2016-04-30 at 1.52.32 PMThis pathway is located in the anterior and alteral white funiculi of the spinal cord. It is composed of the anterior spinothalamic tract and the lateral spinothalamic tract. Axons projecting from primary neurons enter the spinal cord and synpase on secondary neurons within the posterior horns. Axons entering these pathways conduct stimuli related to crude touch and pressure as well as pain and temperature. Axons of the secondary neurons in the anterolateral pathway cross over to the opposite side of the spinal cord before ascending toward the brain. This decussation occurs through the anterior white commissure, loacted anterior to the gray commissure. The anterior and lateral spinothalamic pathway, are somatotopically organized: Axons transmitting sensory information from more inferior segments of the body are located lateral to those from more superior segments. Secondary neuron axons synapse on tertiary neurons located within the thalamus. Axons from the tertiary neurons then conduct stimulus information to the appropriate region of the primary somatosensory cortex.

Spinocerebellar Pathway

Screen Shot 2016-04-30 at 1.54.21 PMThe spinocerebellar pathway conducts proprioceptive information to the cerebellum for processing to coordinate body movements. The spinocerebellar pathway is composed of anterior and posterior spino- cerebellar tracts; these are the major routes for transmitting postural input to the cerebellum. Sensory input arriving at the cerebellum through these tracts is critical for regulating posture and balance and for coordinating skilled movements.  ese spinocerebellar tracts are di erent from the other sensory pathways in that they do not use tertiary neurons; rather, they have only primary and second- ary neurons. Information conducted in spinocerebellar pathways is integrated and acted on at a subconscious level.

Anterior spinocerebellar tracts conduct impulses from the inferior regions of the trunk and the lower limbs.  eir axons enter the cerebellum through the superior cerebellar peduncle. Posterior spinocerebellar tracts conduct impulses from the lower limbs, the trunk, and the upper limbs.  eir axons enter the cerebellum through the inferior cerebellar peduncle.

Update on Jul 29 2017


A cross section of the gray matter of the spinal cord shows a number of laminas (layers of nerve cells), termed Rexed's laminae after the neuroanatomist who described them. As a general principle, laminae are involved in non-painful was well as painful sensation.

Lamina I – This thin marginal layer contains neurons that respond to noxious stimuli and send axons to the contralateral spinothalamic tract.

Lamina II – Also known as substantia gelatinosa, this lamina is made up of small neurons, some of which respond to noxious stimuli. Substance P, a neuropeptide involved in pathways mediating sensibility to pain, is found in high concentration in laminas I and II.

Lamins III and IV – These are referred to together as the nucleus proprius. Their main input is from fibers that convey position and light touch sense.

Lamina V – This layer contains cells that respond to both noxious and visceral afferent stimuli.

Lamina VI – This deepest layer of the dorsal horn contains neurons that respond to mechanical signals from joints and skin.

Lamina VII – This is a large zone that contains the cells of the dorsal nucleus (Clarke's column) medially as well as a large portion of the ventral grapy column. Clarke's column contains cells that give rise to the posterior spinocerebellar tract. Lamina VII also contains the intermediolateral nucleus (or intermediolateral cell column) in thoracic and upper lumbar regions. Preganglionic sympathetic fibers project from cells in this nucleus, via the ventral roots and white rami communicantes, to sympathetic ganglia.

Laminas VIII and IX – These layers represent motor function neuron groups in the medial and lateral portions of the ventral grapy column. The medial portion (also termed the medial motor neuron column) contains the LMNs that innervate axial musculature. The lateral motor neuron column contains LMNs for the distal muscles of the arm and leg. In general, flexor muscles are innervated by motor neurons located close to the central canal, whereas extensor muscles are innervated by motor neurons located more peripherally.

Lamina X – This represents the small neurons around the central canal or its remnants.

Ascending Fiber System

All afferent axons in the dorsal roots have their cell bodies in the dorsal root ganglia. Different ascending systems decussate at different levels. In general, ascending axons synapse within the spinal cord before decussating.

Dorsal column tract

These tracts, which are part of the medial lemniscal system, convey well-localized sensations of fine touch, vibration, two-point discrimination, and proprioception (position sense) from the skin and joints; they ascend, without crossing, in the dorsal white column of the spinal cord to the lower brain stem. The fasciculus gracilis carries input from the lower half of the body, with fibers that arise from the lowest, most medial segments. The fasciculus cuneatus lies between the fasciculus gracilis and the dorsal gray column; it carries input from the upper half of the body, with fibers from the lower (thoracic) segments more medial than the higher (cervical) ones. Thus, one dorsal column contains fibers from all segments of the ipsilateral half of the body arranged in an orderly somatotopic fashion from medial to lateral.

Ascending fibers in the gracile and cuneate fasciculi terminate on neurons in the gracile and cuneate nuclei (dorsal column nuclei) in the lower medulla. These second-order neurons send their axons, in turn, across the midline via the lemniscal decussation (also called the internal arcuate tract) and the medial lemniscus to the thalamus. From the ventral posterolateral thalamic nuclei, sensory information is relayed upward to the somatosensory cortex.

Spinothalamic tract

Small-diameter sensory axons conveying the sensations of sharp (noxious) pain, temperature, and crudely localized touch course upward, after entering the spinal cord via the dorsal root, for one or two segments at the periphery of the dorsal horn. These short, ascending stretches of incoming fibers that are termed the dorsolateral fasciculus, or Lissauer's tract, then synapse with dorsal column neurons, especially in laminas I, II, and V. After one or more synapses, subsequent fibers cross to the opposite side of the spinal cord and then ascend within the spinothalamic tracts, also called the ventrolateral (or anterior system). These spinothalamic tracts actually consist of two adjacent pathways: The anterior spinothalamic tract carries information about light touch, and the lateral spinothalamic tract conveys pain and  temperautre sensibility upward. 

The spinothalamic tracts, like the dorsal column system, show somatotopic organization. Sensation from sacral parts of the body is carried in lateral parts of the spinothalamic tracts, whereas impulses originating in cervical regions are carried by fibers in medial parts of the spinothalamic racts. Axons of the spinothalamic tracts project rostrally after sending branches to the reticular foramtion in the brain stem and project to the thalamus.

The second-order neurons of both the dorsal column system and spinothalamic tracts decussate. The pattern of decussation is different, however. The axons of second-order neurons of the dorsal column system cross in the lemniscal decussation in the medulla; these second-order sensory axons are called internal arcuate fibers where they cross. In contrast, the axons of second-order neurons in the spinothalamic tracts cross at every segmental level in the spinal cord. This fact aids in determining whether a lesion is in the brain or the spinal cord.

With lesions in the brain stem or higher, deficits of pain perception, touch sensation, and proprioception are all contralateral to the lesion. With spinal cord lesions, however, the deficit in pain perception is contralateral to the lesion, whereas the other deficits are ipsilateral.

Spinocerebellar tract

Two ascending pathways (of lesser importance in human neurology) provide input from the spinal cord to the cerebellum.

Dorsal spinocerebellar tract – Afferent fibers from muscle and skin enter the spinal cord via dorsal roots at levels T1 to L2 and synapse on second-order neurons of the nucleus dorsalis (Clarke's column). Afferent fibers originating in sacral and lower lumbar levels ascend within the spinal cord (within the dorsal columns) to reach the lower portion of the nucleus dorsalis.

The dorsal nucleus of Clarke is not present above C8; it is replaced, for the upper extremity, by a homologous nucleus called the accessory cuneate nucleus. Dorsal root fibers originating at cervical levels synapse with second-order neurons in the accessory cuneate nucleus.

The second-order neurons from the dorsal nucleus of Clarke form the dorsal spinocerebellar tract; second-order neurons from the lateral cuneate nucleus form the cuneocerebellar tract. Both tracts remain on the ipsilateral side of the spinal cord, ascending via the inferior cerebellar peduncle to terminate in the paleocerebellar cortex.

Ventral spinocerebellar tract – This system is involved with movement control. Second-order neurons, located in Rexed's laminae V, VI, and VII in lumbar and sacral segments of the spinal cord, send axons that ascend through the superior cerebellar peduncle to the pale ocerebellar cortex. The axons of the second-order neurons are largely but not entirely crossed.