case 7 - teach me physiology Flashcards
what is the glomerulus
a loop of capillaries twisted into a ball shape, surrounded by the Bowman’s capsule
what occurs in the glomerulus
ultrafiltration of the blood, the first step in urine production
what are the three components of the filtration barrier
endothelial cells of the glomerular capillaries
glomerular basement membrane
epithelial cells of Bowman’s capsule
what are the epithelial cells of Bowman’s capsule also called
podocytes
what are the perforations called in the glomerular capillary endothelium
fenestrae which are pores
what does these pores not do
they do not restrict the movement of water and proteins or large molecules but instead prevent the filtration of blood cells
what surrounds the luminal surface of the endothelial cells
the glycocalyx consisting of negatively charged glycosaminoglycans
what does this glycocalyx function to do
functions to hinder the diffusion of negatively charged molecules by repelling them due to like charges
what is the basement membrane that surrounds the capillary endothelium mostly made up
type IV collagen, heparan sulfate proteoglycans and laminin
what do heparan sulfate proteoglycans help do
help restrict the movement of negatively charged molecules across the basement membrane
what are the three layers of the basement membrane
An inner thin layer (lamina rara interna)
A thick layer (lamina densa)
An outer dense layer (lamina rara externa)
what do these layers help do
help limit the filtration of intermediate and large sized solutes
what are podocytes
Podocytes are specialised epithelial cells of Bowman’s capsule which form the visceral layer of the capsule.
what forms filtration slits
foot-like processes project from these podocytes and interdigitate to form filtration slits
what are these filtration slits bridged by
a thin diaphragm
what do the pores in this diaphragm stop from corssing
proteins
what is the process by which blood filters into the Bowman’s capsule
ultrafiltration
what is ultrafiltration
simply filtration that occurs under pressure. in this case, the afferent and efferent arterioles are responsible for generating pressure
where is the afferent arteriole
at the proximal glomerulus
what does this afferent arteriole do
it dilates, while the efferent arteriole at the distal glomerulus constricts
what does this create
a pressure gradient throughout the glomerulus, causing filtration under pressue
what is the filtration rate of molecules of the same charge across the filtration barrier inversely related to
their molecular weight
what molecules filter less easily
Negatively charged large molecules filter less easily than positively charged ones of the same size.
what are the final two segments of the kidney nephron
the DCT and the CD
what is the role of the early DCT
The role of the early DCT is the absorption of ions, including sodium, chloride and calcium. It is impermeable to water.
what are situated in the first segment of the DCT
macula dense
what do the macula densa do
they are sensory epithelium involved in tubuloglomerular feedback.
what does this tubuloglomerular feedback allow for
allows for control of GFR and blood flow within the same nephron the sente
what is the movement of these ions dependent on in the EDCT
Movement of these ions is dependent on the Na+/K+-ATPase transporter on the basolateral membrane of the cells.
what does this excrete
this excrete sodium ions into the extracellular fluid, and brings potassium ions into the cell
what does this channel do
reduces intracellular sodium levels, creating a gradient which favours movement of sodium into the cell via other channels on the apical membrane
what type of process is this
this process is primary active transport, as ATP is directly needed to set up the gradient
what does this sodium concentration gradient generated allow for
allows sodium to enter the cell from the lumen of the DCT, which occurs through the NCC symporter alongside chloride ions
what happens to the chloride ions
they then exit the cell through a chloride ion uniporter on the basolateral membrane into the extracellular fluid, preventing accumulation within the cell
what inhibit the NCC
thiazide diuretics
what also utilises the sodium gradient established in the Na+K+ATPase channel
ca2+ absorption
what is the sodium calcium antiporter and where is it found
on the basolateral membrane and it is called the NCX channel
what is this channel responsible for
This is responsible for transporting calcium ions out into the extracellular fluid, and sodium ions into the cell. The reduction in intracellular calcium creates a gradient which draws calcium ions from the lumen of the tubule into the cell, through a calcium ion uniporter. Since ATP is not directly required, this is secondary active transport.
what also acts here
parathyroid hormone - binding of PTH to its receptor causes more Ca2+ channels to be inserted and increases Ca2+ reabsorption
what are the two types of cells in the Late distal convuluted tubule and collecting duct
principal cells and intercalated cells
what are principal cells mainly involved in
the uptake of sodium ions and extrusion of potassium ions
what is this exchange driven by
This exchange is, again, driven by a Na+/K+-ATPase on the basolateral membrane This sets up a gradient for sodium to enter the cell through ENaC channels (epithelial Na+ channel).
what factors promote secretion of potassium ions into the lumen of the tubule through a potassium uniporter
Sodium ions are positively charged, so as they are extruded an electrical gradient is formed. Additionally, potassium ions accumulate within the cell due to the Na+/K+-ATPase.
what are intercalated cells
they assist in acid-base control, by controlling the levels of hydrogen and bicarbonate ions
what do type A intercalated cells do
they utilise hydrogen ATPase and H+K+ATPase transporters to secrete H+ into the lumen, whilst reabsorbing bicarbonate
what is bicarbonate formed by
Bicarbonate is formed intracellularly by carbonic anhydrase acting on carbon dioxide and water (similarly to in the PCT).
what is the difference between the PCT and type A intercalated cells
is that these cells can actively secrete H+ into the lumen against a large concentration gradient, allowing for H+ secretion in response to acidosis
what happens once the hydrogen is in the lumen of the tubule
the hydrogen ions react with either phosphate (HPO42-) or ammonia (NH3). This prevents the ions from re-entering the cell, as both new compounds (NH4+ and H2PO4–) are charged. Hence, they are unable to travel back across the membrane, and so are excreted.
what prevents an accumulation of chloride ions and potassium ions within the cell
a K+/Cl– symporter on the basolateral membrane allows leakage of these ions back into the extracellular fluid.
what do type B intercalated cells have
have H+ and HCO3– channels on opposite sides of the cell. The net effect in type B cells is secretion of HCO3– and reabsorption of H+, important in the body’s response to alkalosis.
what is the main role of the collecting duct
is the reabsorption of water, through the action of ADH and aquaporins
where is ADH produced and stored and what does it act on to do
ADH is produced in the hypothalamus, and stored in the posterior pituitary gland until it is released. This hormone acts on kidney tubules to increase the number of aquaporin 2 channels (water channels) in the apical membrane of collecting duct tubular cells.
what does ADH bind to and what does this activate
ADH binds to V2 receptors on the tubule cells, which activate adenylyl cyclase hence increasing production of cyclic AMP.
subsequently, what happens to the vesicles containing aquaporin 2 channels
vesicles containing the aquaporin 2 channels deposit their contents into the apical membrane of the tubular cells (the basolateral membrane always contains aquaporin 3 and 4 channels, so is always permeable).
what does ADH also act to do
increase urea reabsorption in the medullary collecting duct
what is impermeable to water but permeable to urine
the thick ascending limb of the nephron
what does this result in
This means that the urea is able to pass from the interstitium back into the thick ascending limb down its concentration gradient (urea recycling). Whilst in the interstitium, urea acts as an effective osmole and hence allows greater volumes of water to be reabsorbed in the nephron.
what are the three parts of the nephron
It consists of three parts: the renal corpuscle, the filtering component, the renal tubule, which is responsible for absorption and ion secretion, and the collecting duct, which is responsible for the final reabsorption of water and for storing urine.
what are the three parts of the renal tubule
The renal tubule has 3 components: the proximal convoluted tubule (PCT), the Loop of Henle and the distal convoluted tubule (DCT).
what is the PCT lined with
It is lined with simple cuboidal epithelial cells which have a brush border to increase surface area on the apical side. The epithelial cells have large amounts of mitochondria present to support the processes involved in transporting ions and substances.
what are the two parts of the proximal tubule
pars convolute and pars recta
where is the pars convolute and what can it be divided itno
The pars convolute resides in the renal cortex and it can further be divided into 2 segments; S1 (segment 1) and the proximal part of S2.
what is the pars recta
The pars recta is a straight segment present in the outer medulla. It makes up the distal part of S2 and S3.
what happens in the PCT
A large amount of reabsorption occurs in the proximal convoluted tubule. Reabsorption is when water and solutes within the PCT are transported into the bloodstream. In the PCT this process occurs via bulk transport. The solutes and water move from the PCT to the interstitium and then into peritubular capillaries. The reabsorption in the proximal tubule is isosmotic.
what do the proximal tubules reabsorb
about 65% of water, sodium, potassium and chloride, 100% of glucose, 100% amino acids, and 85-90% of bicarbonate.
what are the two routes through which reabsorption can take place and what do they do
paracellular and transcellular. The transcellular route transports solutes through a cell. The paracellular route transports solutes between cells, through the intercellular space.
what is the driving force for reabsorption in the PCT and what are the features of this transport
The driving force for the reabsorption in the PCT is sodium, due to the presence of many sodium-linked symporters e.g. sodium glucose linked transporters (SGLTs) on the apical membrane. Sodium is usually co-transported with other solutes e.g. amino acids and glucose, or in later segments of the tubule with chloride ions. Thus sodium moving down its concentration allows other solutes to move against their own concentration gradient.
how is the electrochemical gradient for sodium created
Na+-K+-ATPases on the basolateral surface pump out 3 Na+ ions, in exchange for bringing 2 K+ ions into the cell. This transporter uses primary active transport. This movement of Na+ creates an electrochemical gradient favouring the movement of Na+ into the cell from the tubule lumen.
features of the S1 segment of the PCT
it is not permeable to urea and chloride ions, hence their concentration increases in S1 which creates a concentration gradient which can be utilised in the S2 and S3 segements.
where are the Na+/amino acid symporters located
Na+/Amino acid symporters are present on the apical side of cells in the S1 segment of the PCT which reabsorbs all the amino acids in the PCT.
where is the Na+/H+ antiporter found
on the apical surface of PCT cells. It is an antiporter and therefore transports ions across the cell membrane in opposite directions. In this case, the Na+ ions move into the tubular cells, while the H+ is expelled into the lumen. The primary function of this transporter is to maintain the pH.
what happens to the solute concentration as we move along the tubule
solute concentration in the tubule decreases while the solute concentration in the interstitium increases
what does the difference in concentration gradient in water moving result in
The difference in concentration gradient results in the water moving into the interstitium via osmosis. Water mainly takes the paracellular route to move out of the renal tubule but it can also take the transcellular route.
what does the PCT secrete
organic acids and bases
h+ ions
drugs and toxins
features of organic acid and bases secretion
bile salts, oxalate and catecholamines (waste products of metabolism)
features of hydrogen ions secretion
important in maintaining acid/base balance in the body. H+ secretion allows reabsorption of bicarbonate via the use of the enzyme carbonic anhydrase (Fig 2). The net result is for every one molecule of H+ secreted, one molecule of bicarbonate and Na+ is reabsorbed into the blood stream. As the H+ is consumed in the reaction in the tubular lumen, there is no net excretion of H+. In this way, about 85% of filtered bicarbonate is reabsorbed in the PCT (the rest is reabsorbed by the intercalated cells at the DCT/CD later on)..
features of drugs/toxins secretion
Secretion of organic cations such as dopamine or morphine occurs via the H+/OC+ exchanger on the apical side of the tubule cell, which is driven by the Na+/H+ antiporter.
what is the configuration of the Loop of Henle
The Loop of Henle has a hairpin configuration with a thin descending limb and both, a thin and thick ascending limb (TAL).
what are the features of the limbs of the LoH
The thin descending and ascending segments have thin, squamous epithelial membranes with minimal metabolic activity. The TAL has cuboidal epithelial membranes and is quite metabolically active.
what is the descending limb highly permeable to
water, with reabsorption occurring passively via AQP1 channels.
what else is reabsorbed in the descending limb
Small amounts of urea, sodium (Na+) and other ions are also reabsorbed. As mentioned above, water reabsorption is driven by the counter-current multiplier system set up by the active reabsorption of sodium in the TAL.
what is the thin ascending limb impermeable to and why
The thin ascending limb is impermeable to water, due to it having no aquaporin channels.
features of Na+ and Cl- reabsorption in the thin ascending limb
Na+ reabsorption occurs passively through epithelial Na+ (eNaC) channels and Chloride (Cl–) ions are reabsorbed in the thin ascending limb through Cl– channels. There is some paracellular movement of Na+ and Cl– because of the difference in osmolarity between the tubule and the interstitium.
where is the primary site of sodium reabsorption in the LoH
the thick ascending limb
what is the driver of Na+ reabsorption
Sodium reabsorption is active – the driver is the Na+/K+ ATPase on the basolateral membrane which actively pumps 3 Na+ ions out of the cell and 2 potassium (K+) ions into the cell. So by creating a low intracellular concentration of sodium, the inside of the cell becomes negatively charged, creating an electrochemical gradient.
what then happens to sodium
Sodium then moves into the cell (from the tubular lumen) down the electrical and chemical gradient, through the NKCC2 transporter on the apical membrane This transporter moves one Na+ ion, one K+ ion and two Cl– ions across the apical membrane.
what happens to the potassium ions
Potassium ions are transported back into the tubule by renal outer medullary potassium (ROMK) channels on the apical membrane to prevent toxic build up within the cell.
what happens to the chloride ions
Chloride ions are transported into the tissue fluid via CIC-KB channels.
what are the overall effects of the processes in the thick ascending limb
Removal of Na+ whilst retaining water in the tubules – this leads to a hypotonic solution arriving at the DCT.
Pumping Na+ into the interstitial space – this contributes to a hyperosmotic environment in the kidney medulla
what happens in the glomerulus to water and describe the process
In the glomerulus, water is initially filtered out, along with the other solutes e.g. Na+, K+ and glucose. From here H2O needs to be reabsorbed into the tubule cells and then back into the interstitial space. From the interstitial space, H2O can move back into the vasa recta, the blood vessels running alongside the nephron.
where are the 3 main places where H2O reabsorption accurs
the proximal convoluted tubule (PCT), the descending limb of the Loop of Henle and the collecting ducts.
what happens to H20 when Na+ movement makes the tubule intracellular fluid more concentrated than the filtrate
This creates a concentration gradient to drive H2O movement into the tubule cell. This is known as transcellular movement and occurs when H2O molecules move across the cell membrane via aquaporin-1 (AQP-1) channels, driven by osmosis.
what happens once the H2O molecules are in the cell
Once in the cell, H2O molecules then move out of the cell into the cortical interstitial space via another AQP-1 channel on the basolateral surface.
what is the paracellular movement of H20
Paracellular movement of H2O occurs between tubule cells and is due to the higher hydrostatic pressure in the filtrate than in the interstitial space. This forces water between the tubule cells through leaky tight junctions.
what is the transcellular movement of H20
Transcellular movement of H2O effectively bypasses the tubule cell and moves it straight from the filtrate to the interstitial space directly.
what is the result by the end of the PCT
By the end of the PCT, the concentration of water in the filtrate and interstitial space is almost the same. Overall, about 67% of the filtered water is reabsorbed in the PCT.
where does water reabsorption occur in the loop of henle
Water reabsorption occurs in the thin descending limb of the Loop of Henle. It is permeable to water, which means that H2O molecules are freely able to leave it. Similarly to in the PCT, water can leave the thin descending limb into the more concentrated medulla through transcellular and paracellular movement.
what is the driving force behind the movement of water out into the medulla
The driving force behind this is the movement of Na+, Cl– and K+ from the tubule to the medulla, via NKCC symporters in the thick ascending limb. This makes the renal medulla more concentrated, providing an osmotic gradient.
what is water reabsorption driven by in the collecitng duct
In the collecting duct, H2O reabsorption is driven by antidiuretic hormone (ADH). ADH is produced in the hypothalamus and is secreted from the posterior pituitary gland in response to low plasma volume or high osmolality.
where does ADH act and what does this trigger
ADH acts on the principal cells in the collecting duct by binding to receptors. This triggers an intracellular signalling pathway that causes increased aquaporin-2 (AQP-2) production for the apical surface of the principal cell. The water can then move through the tubule and back into the renal medulla. Similarly to in the Loop of Henle, the force driving this movement is the high concentration of Na+ in the renal medulla.
how does blood move from the interstitial space back into the circulation
via the vasa recta
what does the concetrated vasa recta result in
water moves into it via osmosis
