APPP 04 and 07: Kidney Flashcards

Question

What is the other way that urine formation occurs?

Answer 1

as filtered fluid leaves Bowman's capsule and passes through tubules, it is modified by reabsorption of water and specific solutes back into the blood (active and passive transport depending on substance and site) or by secretion of other substances from the peritubular capillaries into the tubule - 125 ml/min is the amount of fluid which leaves the glomerular capillaries to go into the glomerular space (GFR) but only 1 ml/min is excreted in urine - blood exits through the efferent arteriole

Answer 2

in general, tubular reabsorption is quantitatively more important than tubular secretion

Answer 3

- glomerular filtration is relatively non-selective – all solute in the plasma are filtered except the plasma proteins - tubular reabsorption is highly selective

Answer 4

some substances like glucose and amino acids are almost completely reabsorbed from tubules so that the urinary excretion rate is essentially zero

Answer 5

certain waste products like urea and creatinine are poorly reabsorbed from the tubules and excreted in relatively large amounts

Answer 6

- K+ - H+ - urea - some drugs like thiazides

Answer 7

kidneys can regulate the excretion of solutes by controlling the rate at which they reabsorb different substances

Answer 8

propelled down the ureter to the bladder where it is stored, and eventually excreted via the urethra

Answer 9

a protease produced and secreted by the juxtaglomerular cells (JGC)

Answer 10

specialized set of smooth muscle cells that line the afferent and efferent arterioles

Answer 11

- a direct pressure sensing mechanism within the afferent arteriole – decreased blood pressure increases renin release - sympathetic innervation of the JGC promotes renin release via beta1-adrenoceptor signaling – stimulation of beta1 receptors increases renin release - specialized cells within the distal tubule called macula densa that is especially sensitive to electrolyte concentration (especially NaCl) – decreased luminal NaCl delivery increases JGC renin release

Answer 12

- plasma renin cleaves the circulating angiotensin (large plasma protein) formed by the liver to the decapeptide angiotensin I (ATI) - then ATI is cleaved to the active octapeptide angiotensin II (ATII) by angiotensin converting enzyme (ACE)

Answer 13

- highly expressed in the pulmonary vascular endothelium - also present in endothelial cells lining the coronary arteries and blood vessels in the kidneys

Answer 14

- stimulation of aldosterone secretion from the adrenal cortex (which promotes renal tubular reabsorption of NaCl) - arteriolar vasoconstriction

Answer 15

thirst and antidiuretic hormone (ADH/vasopressin) secretion

Answer 16

(these actions increase intravascular volume and blood pressure) - can increase peripheral vascular resistance and therefore blood pressure by actin on the V1 receptor - can promote absorption of water by stimulating the V2 receptor in the cells of the collecting duct – as a consequence, aquaporin (specifically AQ2) or water channels are translocated to the plasma membrane and water is absorbed into the blood

Answer 17

passive and active mechanisms - simple diffusion - channel-mediated diffusion - carrier-mediated (facilitated) diffusion - co-transport - counter transport - ATP-mediated transport

Answer 18

solutes with sufficient lipid solubility may diffuse across the membrane down concentration gradients

Answer 19

diffusion of solute through a pore formed by membrane proteins

Answer 20

transport of solute by carrier protein down electrochemical gradient

Answer 21

co-transport of solutes in the same direction - ie. simultaneously transports both Na+ and another solute Cl- or glucose from the tubular lumen into the renal epithelial cell

Answer 22

counter transport of solutes in the opposite direction - ie. transports Na+ in, another solute H+ out of renal epithelial cells

Answer 23

transport of solute by carrier protein against an electrochemical gradient with aTP hydrolysis providing the driving force

Answer 24

ATP-mediated transport that functions throughout most parts of the renal tubule - present on the basolateral side of the tubular epithelial cell - cell membrane has an extensive Na+-K+ ATPase that hydrolyzes ATP and uses the released energy to transport Na+ ions out of the cell into the interstitium and eventually into the peritubular network - at the same time, K+ is transported from the interstitium to the inside of the cell (3 Na+ ions are ejected from the cell, while 2 K+ ions gain entry) - maintains low intracellular Na+ - creates a net negative charge within the cell - this favours movement of Na+ across the luminal membrane (either via carrier proteins or Na+ channels) into epithelial cells - as Na+ diffuses down its electrochemical gradient, the energy released is used to co-transport (like glucose, amino acids, and chloride) or counter-transport (like H+ ions) other substances

Answer 25

about 65-70% of the filtered load of Na+ and water, and a slightly lower % of filtered Cl- are reabsorbed by the proximal tubule before it reaches the loop of Henle

Answer 26

- highly metabolic - have large numbers of mitochondria to support potent active transport processes - have an extensive brush border (densely packed microvilli to provide an extensive membrane surface area)

Answer 27

although the amount of Na+ in the tubular fluid decreases markedly along the proximal tubule, the concentration of Na+ remains relatively constant because water permeability of the proximal tubule is so great that water reabsorption keeps pace with Na+ reabsorption

Answer 28

sodium-hydrogen exchanger (NHE3)

Answer 29

- apical side of the cell membrane (CAIV) - cytosol (CAII)

Answer 30

catalyzes the hydration of CO2 and dehydration of CA (H2O + CO2 ↔ H2CO3 ↔ HCO3- + H+) - CAIV catalyzes the cleavage of carbonic acid into water and CO2 (which diffuses into the cytoplasm of the proximal epithelial cells - CAII rapidly rehydrates intracellular CO2 to carbonic acid - this eventually leads to the formation of HCO3- which is then co-transported with Na+ across the basolateral membrane of the epithelial cell by Na+-HCO3- co-transporter NBC1 - permeability of the luminal membrane of the proximal tubule to HCO3- is poor, therefore reabsorption of HCO3- by the proximal tubule is dependent on CA activity

Answer 31

catalyzes the cleavage of carbonic acid into water and CO2 (which diffuses into the cytoplasm of the proximal epithelial cells

Answer 32

rapidly rehydrates intracellular CO2 to carbonic acid

Answer 33

parallels that of Na+ and water - reabsorption is thought to occur mainly by passive diffusion and solvent drag (refers to solutes in the ultrafiltrate that are transported back from the renal tubule by the flow of water rather than specifically by ion pumps or other membrane transport protein - passive paracellular pathways account for approximately 80% of Ca2+ reabsorption in this segment of the nephron

Answer 34

secrete a variety of substances like uric acid and diuretics to the luminal fluid from the blood - helps to deliver diuretics to the luminal side of the tubule where most of them are active

Answer 35

proximal tubule is a key location

Answer 36

couple glucose with sodium

Answer 37

responsible for reabsorption of 90% of glucose filtered in the glomerulus back into the bloodstream - present in S1 and S2 convoluted section of the proximal tubule

Answer 38

responsible for reabsorption of the remaining 10% of filtered glucose - present in the S3 or straight segment of the proximal tubule

Answer 39

facilitate insulin independent reabsorption of filtered glucose

Answer 40

- at normal levels, the amount of glucose filtered by the glomerulus increases with glycaemia and is entirely reabsorbed from the proximal tubule by SGLT-2 transporters – NO GLYCOSURIA - beyond a given glycaemia (the renal threshold for glucose RTg), this reabsorption mechanism becomes saturated and glucose appears in the urine – GLYCOSURIA

Answer 41

- descending thin segment - ascending thin segment - thick ascending segment

Answer 42

- freely permeable to water

Answer 43

- virtually impermeable to water, which remains in the tubule - about 20-25% of the filtered loads of Na+, Cl-, and K+ are reabsorbed - Na+-K+ ATPase pump maintains a low intracellular Na+ concentration, which in turn provides a favourable gradient for movement of Na+ from the tubular fluid into the cell

Answer 44

primarily by 1-sodium, 1-potassium, 2-chloride co-transporter (NKCC2) - by taking K+ from the lumen into the epithelial cell, which also gains K+ from the interstitial fluid via Na+-K+ ATPase pump, there is backflow of K+ into the lumen - this creates a trans-epithelial voltage along the thick ascending limb that is oriented such that the lumen is positive relative to the interstitial fluid - this drive the paracellular reabsorption of luminal divalent cations like Mg2+ and Ca2+

Answer 45

electro neutral co-transporter

Answer 46

part of the juxtaglomerular complex – where the distal convoluted tubule comes in contact with the afferent arteriole - at this junction, distal tubular cells become highly specialized (referred to as macula densa) and respond to changes in Na+ - typically, activation of the macula densa triggers highly specialized cells lining the afferent arterioles (granular juxtaglomerular cells) to release renin into the bloodstream

Answer 47

- has many of the reabsorptive characteristics of the thick segment of the ascending limb of the loop of Henle - contains the sodium-chloride co-transporter (NCC)

Answer 48

- about 4-5% of filtered Na+ in the glomerular filtrate - mediates the reabsorption of luminal Ca2+ via ion-specific Ca2+ channels (TRPV5) in the apical membrane, under the control of the parathyroid hormone – reabsorbed Ca2+ can then cross the distal tubule basolateral membrane via specific Na+-Ca2+ exchangers and Ca2+-ATPases (that exchanges internal calcium for external H+)

Answer 49

in the presence of decrease extracellular Ca2+ levels, reduced activation of the calcium-sensing receptor (CaSR) in the parathyroid glands results in a rapid release of parathyroid hormone (PTH) secretion – PTH acts on: - PTH1 receptor (PTH1R) in the kidneys - CYP27B1 in the proximal tubule - PTH1 receptor in the bone

Answer 50

increases tubular calcium reabsorption by activating TRPV5

Answer 51

promotes the conversion of inactive vitamin D to active vitamin D (also known as calcitrol) - calcitrol acts on the intestine to increase absorption of dietary calcium via vitamin D receptor (VDR)

Answer 52

increases osteoclast (that breaks down bone tissue) activity, resulting in a transfer of calcium from bone tissue to the blood

Answer 53

sodium and water - less than 4-5% of the filtered Na+

Answer 54

aldosterone - secreted from the adrenal cortex - regulates reabsorption of Na+ and its couples secretion of K+ – increases the synthesis of proteins including the Na+ channel and Na+-K+ ATPase in addition to causing mitochondrial biogenesis - reabsorption of Na+ can increase blood volume and blood pressure

Answer 55

cells of the collecting duct have ion channels for Na+ and K+ - as there is only one ion (Na+) that is being absorbed (no other accompanying ion is being co-transported or counter-transported), Cl- and HCO3- are left behind, making the lumen negative (as much as -50 mV) - this is the driving force that draws K+ out of the cell through the apical membrane K+ channel, resulting in K+ secretion - this is also the driving force to move Cl- back into the blood via the paracellular pathway

Answer 56

hormonally controlled by the level of ADH/vasopressin, in contrast to the proximal tubule - ADH secreted from posterior pituitary increases the permeability of the ducts to water, thereby concentrating the urine - ADH stimulates a G-protein coupled receptor in the basolateral membrane (V2 receptors) - cAMP produced due to this activation promotes the insertion of pre-formed water channels called aquaporin-2 (AQP2) into the apical membrane - passive reabsorption of water is the end result (diabetes insipidius)

Answer 57

deficiency of ADH results in large volumes of urine being excreted

Answer 58

non-endothelial renal interstitial cells that are also called interstitial fibroblasts

Answer 59

under physiologic, non-stimulated conditions, a small number of renal EPCs are responsible for renal erythropoietin output - the size of the EPC pool is regulated in an oxygen-dependent manner and increases under hypoxic conditions - expansion of the EPC pool (and increase in erythropoietin) requires hypoxia-inducible factor (HIF-2) signaling, which is activated by hypoxia - tubular epithelial cells do not produce erythropoietin (EPO)

Answer 60

the principal hormonal regulator of erythropoiesis

Answer 61

EPCs transdifferentiate into myofibroblasts, which synthesize collagen and lose their ability to produce EPO

Answer 62

decreased oxygen transport causes tissue hypoxia, which through activation of the HIF system stimulates the production of EPO - EPO stimulates the proliferation and differentiation of erythroid progenitors (more specific than a stem cell) into reticulocytes (immature RBCs) and prevents their apoptosis (cell death) - more reticulocytes enter circulating blood, differentiate into erythrocytes (nucleus is ejected), thus increasing the pool of RBCs

Answer 63

- for iron to be taken up from the intestine, divalent metal transporter 1 (DMT1) is the major iron uptake system of intestinal cells - inside these cells, ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion - this iron can also use ferroportin to be transferred to transferrins that are iron-binding blood plasma proteins that control the level of free iron in biological fluids - hepcidin acts on intestinal cells to decrease the amount of iron absorbed into the body – does so by binding to iron transporter ferroportin, which causes ferroportin to be internalized and degraded - as a result, more iron remains within the intestinal cell so that the iron that enters this cell gets bound to ferritin - in the condition where EPO is decreased, a reduction in erythropoiesis means that the erythroblast decreases erythroferrone production - hepcidin (secreted from the liver) is maintained at higher levels by decreased erythroferrone production - an increase in hepcific negatively affects iron absorption and mobilization (and explains the anemia associated with renal disease)