Renal Physiology ( 15% ) Flashcards

Question

With respect to the counter current system * The loops of Henle act as counter current exchangers. * Solutes diffuse out of vessels conducting blood towards the cortex * Water diffuses out of the ascending vessels. * Water diffuses into the collecting ducts. * Counter current exchange is passive and can operate even if counter current multiplication ceases.

Answer 1

**Solutes diffuse out of vessels conducting blood towards the cortex** ***ie the ascending LoH*** * The loops of Henle act as counter current *multipliers*. * LOH = CC multipliers. Vasa recta = CC exchangers * Water *does not* diffuses out of the ascending vessels, *as they are* *Impermeable to water* * Water diffuses *out of* the collecting ducts, *assuming ADH is present* * Counter current exchange is passive, *but relies on CCM to set up its gradients or it ceases to function.*

Answer 2

**isotonic in the PCT** * *hypertonic* in the *descending* loop of Henle. * *hypotonic* in the DCT. * hypotonic *early* in the collecting duct, *but if ADH is present can be very hypertonic by the end*

Answer 3

**ADH increases the permeability of water by causing the rapid insertion of water channels into the luminal membrane.** *This occurs in the CD. PCT has aquaporin 1 in basolateral and apical membrane, and is not triggered by ADH*

Answer 4

**relatively impermeable to water** *Reabsorbs solutes but less than thick asceding LoH i think*

Answer 5

**Is impermeable to water** * *Thin ascending LoH h*as maximal permeability to NaCl * Is relatively *impermeable* to water. * Is *somewhat permeable* to NaCl. * Is a site where there *_is_* active transport of Na.

Answer 6

**Increased urine flow is due to decreased water resorption in the proximal tubule and loop of Henle** * urine flows are much *more* than in water diuresis. * ADH secretion *Can approach maximal* * The concentration of the urine is *more* than plasma * Osmotic diuresis can be produced by sugars such as mannitol, *and* *a**ny solute that is filtered but not absorbed*

Answer 7

**The concentration of sodium delivered to the loop of Henle falls** * The sodium concentration in the interstitium of the PCT *rises* *as less water is absorbed* * *cf LoH and CD where the interstitial osmo falls as less Na is reabsorbed -\> less osmotic gradients -\> lower interstitial Na load* * Increased fluid load but *increased* sodium load to the DCT (*but reduced sodium concentration)* * The concentration gradient in the medullary pyramid *f**alls* * Volumes of urine are *more than* a pure water diuresis.

Answer 8

**Increased urine flow is due to decreased water reabsorption in the PCT and loops** * In osmotic diuresis the amount of water reabsorbed in PCT is *reduced* * Na reabsorption from the proximal tubules is *impaired* by high osmotic load * Medullary hypertonicity is *decreased* * ADH *allows* the concentration of urine to approach that of plasma.

Answer 9

**long term lesions of the cauda equine produce a dilated thin walled bladder** * Initially thin walled and overfilled, but with time reflex contactions return resulting in a small hypertrophied bladder that causes dribbling of urine.* * Afferent nerve damage causes a dilated thin-walled bladder*

Answer 10

**Sympathetic nerves play no role in micturition** * Contraction of the *detrusor (circular muscle)* is mainly responsible for emptying of the bladder. * The relationship between bladder volume and intravesical pressure has a linear relationship *only at part Ib, which is a partially filled bladder* * The first urge to urinate is produced at *350mL* * Urine in the female urethra empties by *gravity. In males a few contractions of bulbocavernosus is needed to empty the urethra.*

Answer 11

**Initiated by the pelvic nerves** * Co-ordinated in the *sacral* portion of the spinal cord. * Initiated at a volume of *350mL* * *Not at all* affected by sympathetic nerves * *Inherently a spinal reflex, but can be* facilitated *or inhibited* at the level of the brain stem

Answer 12

**Shares a common carrier with glucose.** ***SGLT - secondary active reabsorption of glucose*** * Reabsorbs *60%* of the filtered sodium load * *Na reabsorption in the PCT carries water with it, so fluid remains isotonic* * *Na/H is a passive exchanger, utilising the conc gradient set up by Na-K-ATPase in the basolateral membranes*

Answer 13

Thin descending limb of the loop of Henle

Answer 14

*Does not appear to be a correct answer* * it moves *passively* out of the proximal tubule, *by facilitated diffusion through channels* * *An amount equal to that reabsorbed is secreted back into the LoH (~50% total)* * it plays *a large part (50%)* in the establishment of an osmotic gradient in the medullary pyramids. * *Urea is reabsorbed in the PCT, DCT, and primarily the CD* * a high protein diet *increases* the ability of the kidneys to concentrate urine, *as there is more urea* * *ADH causes increased urea reabsoprtion (increasing the concentrating ability of the kidney) by increasing the number of transporters in the CD*

Answer 15

**the thin part of the ascending loop of Henle is *impermeable* to water**

Answer 16

Free water clearance = flow - ((urine osm x flow) / Plasma osm) =200 - (450 x 200)/300 = 200 - (90000 / 300) **= -100ml/hr**

Answer 17

**ANP produces a diuresis through *downregulation of ENaC in the CD*** * Ang II increases Na-H exchanger in PCT* * Aldosterone upregulates ENaC in CD (counteracts ANP)*

Answer 18

**K secretion is increased in conditions of alkalosis.** *As K is reabsorbed in the CD in exchange for H (H-K-ATPase), so in alkalosis, H+ will be reabsorbed, increasing K excretion.* * The rate of K excretion is *proportional* to the rate of flow of tubular fluid, *as rapid flow does not allow [K] to reach a value that stops secretion* * Hypoaldosteronism produces *decreased* urinary K levels, *as there is less Na-K-ATPase activty, hence less K excretion* * Carbonic anhydrase inhibitors *increase* the excretion of K. * CA inhibitors result in reduced H+ secretion (create an alkalotic urine/serum acidosis), with resultant increase in Na+ and K+ secretion * Increased Na delivery to the collecting ducts leads to increased K *secretion*. * Potassium is secreted in CD, and increased Na delivery will likely enhance secretion as urine tubular flow will be increased

Answer 19

**The rate of K secretion is proportionate to the rate of flow of tubular fluid in the distal nephron** * K is actively *secreted* in the DCT. * K excretion is *increased* when H secretion is decreased. * K-H-ATPase exchanges K for H, so if the excretion of one is increased, the other will decrease * K *does* compete with H in tubular fluid * K is *secreted* and Na *reabsorbed* in DCT. * Na is never excreted in the kidneys. Potassium is first absorbed along with Na, then excreted in DCT

Answer 20

**Most of the Na is actively transported out of the tubular cell into the lateral intercellular spaces** * Na is actively transported out of *most* parts of the renal tubule, *except the thin loops* * Na is *not* pumped out of the thin portion of the loop of Henle by Na/K ATPase, *as it is not transported out of the thin loop, but also is not 'pumped' out, it follows a concentration gradient set up by basal Na-K-ATPase.* * The N/K ATPase extrudes *3 Na out for 2K in* of the tubular cell. * Around *99% (97-100% depending on aldosterone)* of Na is reabsorbed back into the circulation

Answer 21

**pH of 4.5 in the urine is the limiting pH for H secretion** * K secretion in DCT and collecting ducts mainly occur through *H+* dependent transport mechanism. * for each H secreted, *1* Na ions is reabsorbed * the H secretion in the PCT is mainly dependent on *2’ active transport (Na-H exchanger)* * the carbonic anhydrase inhibitors *decresases* H secretion *(alkaline urine, acid plasma)*

Answer 22

**Glucose is reabsorbed by 2ndary active transport** * Glucose is *absorbed by 2’ active transport in PCT (Na-glucose co-transporter)* * The renal threshold refers to glucose *loss* from the urine * Nick questions why this was wrong - techinically it is the threshold at which glucose cannot by reabsorped any longer. Unclear why it is wrong but I have taken a guess above. * “RT for glucose is the plasma level at which glucose first appears in the urine in more than normal minute amounts” * Glucose is reabsorbed in the *PCT* * The glucose carrier in the kidney is *SGLT from tubule to cell, and GLUT from cell to interstitium*

Answer 23

**5% of filtered water is removed by the DCT** * At the end of the PCT *60%* of filtered water is resorbed. * *At least 87%* of filtered water is reabsorbed when the urine volume is 23L in 24hours * *15%* of filtered water is removed by the loop of Henle. * total solute excretion over 24 hours *is generally fairly stable, and dependent on solute load.*

Answer 24

**Glucose is removed from the urine by secondary active transport** * 100% glucose is absorbed in the *PCT* * the calculated renal threshold for glucose is *higher* than its actual value.

Answer 25

**Na is actively transported out of all parts of the renal tubule except for the *thin descending limb of LoH*** *In all other places it is actively absorbed by basolateral Na-K-ATPase setting up concentration gradients that allows it to use channels (ENaCs), cotransporters (Na-K-2CL, SGLT etc), or exchangers (Na-H)* * *96-99%* of the total filtered sodium load is reabsorbed. * *a majority* of Na is actively transported via the lateral intercellular spaces. * Na transport is coupled to the movement of *H, glucose, amino acids, and phosphates*. * The Na/H exchanges in the proximal tubule *absorbs* one Na for every H *extruded*

Answer 26

**tubuloglomerular feedback ensures a constant proportion of Na is reabsorbed for any change in the GFR** * is actively transported out of all parts of the renal tubule except the *descending LoH and CD* * changes in aldosterone concentration takes *30min* before an appreciable change to sodium reabsorption is noted*, due to non-genomic action (stimulation of Na-K-ATPase)* * increasing intracellular Ca concentration inhibits sodium reabsorption * most of the Na/H exchange by active transport is performed in the *PCT*

Answer 27

**the first part of the DCT is impermeable to water** * At least *87%* is reabsorbed * *65%* of the filtered water is reabsorbed by the end of the PCT. * *solutes* tends to recirculate in the medullary pyramids, *water is absorbed back into the systemic circulation* * decreasing the tonicity in the medulla *impairs the ability to produce concentrated urine, as concentration gradients arent as large*

Answer 28

**Cl** * HCO3 was given as correct but I think is wrong* * 60% of Na reabsorption occurs in the PCT, as a result of Na-H exchange* * Chloride almost always follows Na shifts in order to preserve electroneutrality - this is the answer on another question which does not include HCO3 as an option* * Indirecly HCO3 is taken up, as H2O and CO2 (products of carbonic anhydrase)*

Answer 29

**is actively reabsorbed in the PCT** * Passively *secreted* in the DCT. * secretion *does* undergo adaptation, *and generally matches K intake* * excretion is *decreased* when H ion secretion is increased. * excretion is *dependent on* Na concentration in the distal tubular fluid *- low Na reaching the distal tubule causes a reduction in K excretion.*

Answer 30

**Inner medullary portion of the collecting tubule** * Absorbed by urea-channels by facilitated diffusion.* * When ADH is high, more urea is reabsorbed, creating a larger diffusion gradient to allow more absorption of water*

Answer 31

**d. Active reabsorption in the proximal tubules** * a. Secretion by *distal* tubule cells * b. Exchange with Na+ on the *interstitial* side via an active pump * c. *active* reabsorption in the *proximal tubules* * e. ???Active exchange with Ca2+ via a K+/Ca2+ exchange

Answer 32

**c. Decreased by atrial natriuretic peptide** * a. Actively transported in the thin portions of the loop of Henle * b. Coupled to the movement of glucose and amino acids in the *proximal* tubule * d. Reabsorbed *down* its concentration gradient * e. *Dependent on* chloride absorption *- Na-2Cl-K cotransporter in Thick ascending limb, and Na-Cl CT in the DCT*

Answer 33

**b. K+ secretion is decreased in acidosis** ***As K is reabsorbed in the CD in exchange for H via the K-H-ATPase*** * a. K+ secretion is mainly by *passive* transport mechanisms *(though this seems to happen more in the CD than DCT)* * c. K+ secretion is *reduced* when Na+ delivery to the tubule is decreased * ????d. Loop diuretics will cause *???* K+ secretion *as they inhibit the Na-K-2Cl cotransporter, leading to more K+ in the urine, and this can lead to a hypokalaemia (and H+ retention)* * e. K+ is reabsorbed by the Na+/K+/2Cl- transporter - *this occurs in the Thick ascending LoH*

Answer 34

**d. Increased urine flow is due to decreased water reabsorption in the proximal tubule and loop of Henle** * a. Urine flows are much *more* than in a water diuresis. * b. Vasopressin secretion is *Normal / elevated (cf water diuresis, where it is almost zero)* * *Body is trying to retain water but unable to overcome the osmotic gradient produced by the osmotic agent* * c. The concentration of the urine is *the same as* plasma. * Water diuresis the urine concentration is lower (osmotic diuresis is due to osmotically active agent in the urine) * e. Osmotic diuresis can be produced by sugars such as mannitol, *as well as* *by NaCl, glucose*

Answer 35

**Angiotensin II increases H secretion from the proximal tubule** *By upregulating Na-H exchanger* * Aldosterone increases K *secretion* from the distal tubule. * Stimulates Na-K-ATPase * ADH increases water reabsorption in the *CD* * ANP decreases Na reabsorption from the *CD* * *ANP / ADH have opposing actions in the CD* * PTH increases PO4 *Excretion*

Answer 36

**Supine position** *The others all create a low BP or low Na state, where not enough Na is getting to the macula densa*

Answer 37

**Angiotensinogen is synthesised by the liver** * Prorenin has *essentially no biologic activity* * Renin secretion will be *decreased* by propranolol, *as it blocks symp nerves* * Angiotensin I *is essentially inert* * Angiotensin II acts at *GPCR* receptors

Answer 38

**Has generally the opposite action to angiotensin II** * *Inhibits* the secretion of vasopressin. * Vasopressin wants to conserve fluid, ANP lose it * Secretion will be *increased* by scuba diving, *as increased pressure outside the body causes an increase in venous pressure -\> increased atrial stretch -\> ANP* * *Pretty sure its mainly hypoxia that* Stimulates EPO production

Answer 39

**Prostaglandins** **(as well as sympathetic nerve activity and catecholamines)** Others all reduce it

Answer 40

**Carbamazepine** * ADH promote water retention.* * Increase: Standing, Angiotensin II, exercise/stress/pain, decreased ECF volume, N+V, increased plasma oncotic pressure* * Decrease: Alcohol, increased ECF volume, decreased plasma osmo*

Answer 41

**Production is inhibited by Theophylline** * Produced in the kidney* * Increases RBC by increasing the number of stem cells* * Causes RBC increase in 2-3 days* * Inactivated in the liver.*

Answer 42

**Inhibits the secretion of ADH** * *Aims to reduce* systolic BP * Increases the responsiveness of vascular smooth muscle to dopamine??

Answer 43

**Prostaglandins increase the secretion of renin** *As do sym nerve activity and catecholamines* * Renin causes *(via Ang I) Ang II to releases aldo* * Angiotensinogen is converted to angiotensin I *by renin in the circulation*. * *Ang I -\> Ang II via ACE in the lungs* * Increased Na reabsorption at the macula densa causes *decreased* renin * Oestrogens *?increase* production of angiotensinogen

Answer 44

**ANP has the greatest affinity for the ANPR-_A_ receptor on the glomerulus**

Answer 45

**Ammonia** *"In chronic acidosis, glutamine synthesis in the liver is increased, using some NH4 which is usually converted into urea, and the glutamine provides the kidneys with another source of NH4"* Acutely, the major buffer systems in the urine (and CSF) are bicarbonate and phosphate. In respiratory acidosis, the renal compensation is through HCO3 (increasing intracellular PCO2 -\> increased H+ secretion due to increased intracellular CA activity, which then combines with HCO3 in the tubule to H2CO3 -\> H20 + CO2 via tubular CA) In metabolic acidosis the buffer systems of HCO3-, NH3-, and HPO4- are used for compensation (otherwise the urine pH would quickly reach 4.5 and no further H+ could be secreted)

Answer 46

**Partly compensated metabolic acidosis** *Slightly acidotic so not completely compensated, but CO2 is reduced in an acidosis so is attempting compensation.*

Answer 47

**Ca** * pCO2 - increases due to increased intracellular CA activity -\> more H+ to secrete * K - Hypokalameia -\> intracellular acidosis (H+ moves intracellularly to compensate for reduced K+), which leads to more H+ excretion * Carbonic anhydrase - inhibition reduces secretion, as less H+ can be produced intracellularly (also increases HCO3 excretion) * Aldosterone - increases activity of H+-ATPase in the DCT to increase excretion.

Answer 48

**High pH, low HCO3 and PaCO2** Uncompensated respiratory alkalosis = pH \>7.45, pCO2 low, bicarb normal/low Low CO2 -\> low intracellular levels -\> less CA activity to convert H20 and CO2 into H+ + HCO3, so there is less H+ excretion and hence less HCO3 reabsorption, further lowering the already low biarb. This helps to reduce the pH towards normal.

Answer 49

**For each H+ secreted in the PCT, one Na and one HCO3 enters the interstitium** * H+ is secreted in the PCT via *Na/H exchange* * *In the DCT it is an ATPase* * *I* cells in the collecting duct actively excrete acid * The limiting urine pH is approximately *4.5* * Carbonic anhydrase in the*PCT* luminal membrane facilitates H+ buffering and the formation of H2CO3 * Then H2CO3 -\> H20 + CO2 which diffuse into cells

Answer 50

**Carbonic anhydrase inhibitors** *Reduces H+ excretion, and creates a metabolic acidosis*

Answer 51

**ADH** * Hypokalaemia -\> increased H+ excretion* * Increased CO2 -\> increased excretion* * CA inhibiton -\> Decreased excretion* * Aldosterone -\> increased excretion (increased ATPase in DCT)*

Answer 52

**the most effective buffers have pK values close to the pH of the environment they operate in** *The closer to the pK, the more they can buffer without a change in pH* * *RBC, kidneys, and lungs* are rich in carbonic anhydrase * *Deoxyhaemoglobin* is better buffer than *oxyhaemoglobin.* * *Thus once Hb has offloaded O2 into the tissues, it is better able to buffer products of metabolism etc on the way back to the lungs* * Phosphate is an important buffer in *intracellular fluid*, *along with protein.* * **Blood buffers are bicarb, protein and Hb. Bicarb is an interstitial buffer * *Metabolic acidosis buffering load is 20% in ECF, 80% ICF*. * For metabolic alkalosis, the ratio is closer to 1:2 (ECF:ICF)

Answer 53

**Base excess is positive** *Because there is more base than acid (hence the alkalosis)* * the ingestion of aspirin *causes a metabolic ACIDOSIS -* (Fixed acid) * Respiratory compensation *cant* restore pH to normal * There is only so much hypoventilation possible before hypoxia stimulates respiratory drive. * Treatment with NaHCO3 *will make this worse, as it is a weak base itself* * There is *less* renal excretion of H ions, *as the body wants to conserve acid*

Answer 54

**Reduction in the pCO2 of alveolar gas** * Fall in pH is not compensatory, it is the thing.* * There will be increased CO2 production likely (increased H+ + HCO3-) to try and remove H+* * Minute volume will increase to remove CO2* * Urine will be acidic as the body excretes acid*

Answer 55

**Dibasic phosphate plays a role in buffering in the distal tubule and the collecting ducts** *Adds H+ to become monobasic phosphate* * Carbonic anydrase in the *PCT* increases the buffering capacity. * The conversion of gluta**_mine_** to glut**_mate_** in the renal tubular cells provide NH3 for buffering. * The largest pH difference between the tubular cells and the lumen occurs across the *DCT or CD* * The *HCO3-* content of the urine increases with serum HCO3 concentrations above 28mmol

Answer 56

**In a few days time they would compensate by lowering HCO3 concentrations** Acute uncompensated respiratory alkalosis, will be compesated with a metabolic acidosis

Answer 57

**Diphosphate** * As well as protein* * ECF = bicarbonate* * Blood = bicarb, protein, Hb*

Answer 58

**Respiratory compensation in metabolic alkalosis is limited by carotid and aortic chemoreceptor response.** *Hypoventilation to compensate for alkalosis can not go so far as to cause hypoxia* * HCO3 concentration will *increase* in compensated respiratory acidosis, *as HCO3 is absorbed in exchange for H+ secretion* * The rate of renal H secretion *increases due to increasing* pCO2 in respiratory acidosis. * Cl excretion is *increased* in respiratory acidosis * Hepatic glutamine synthesis is *increased* in chronic metabolic acidosis, *t**o produce more NH4+ and HCO3- to act as buffers*

Answer 59

**HCO3 reabsorption depends upon the rate of H secretion by the renal tubular cells** * The rate of HCO3 reabsorption is *proportional* to the arterial pCO2 - *increased pCO2 -\> increased HCO3 reabsorption/H+ excretion* * In respiratory acidosis, HCO3 reabsorption is *Increased (see above)* * Changes in plasma Cl concentration are *?inversely* proportional to HCO3 concentrations * In respiratory alkalosis, renal H secretion is *Decreased*

Answer 60

**HCO3** * ICF = protein + phosphate* * Plasma = protein, bicarb, Hb*

Answer 61

**It consists mostly of HPO42-, SO42- and organic acids.** *Increases with increasing negative charge (eg proteins), decreasing positive charge (eg Ca/Mg), or organic anions such as lactate are present (eg lactic acidosis, ketoacidosis)* * It is the difference between cations *other than* Na and anions *other than* Cl and HCO3 * It is *normal* in hyperchloraemic acidosis secondary to ingestion of NH4Cl, *as the Cl is measured in the AG* * It is *increased* when Ca/Mg is decreased * It is *increased* when the albumin is increased

Answer 62

**10** *pKa of HCO3 is 6.1. At this level HCO3 = carbonic acid. An increase of 1 equates to a 10-fold increase in HCO3 (more basic = more bicarb)*

Answer 63

**carbonic anhydrase inhibitors** * Inhibit CA in the cells -\> less H+ secretion, so there is less exchange with K+ so it is excreted* * diuretics cause a hypokalaemic metabolic _alkalosis_ (this happens because there is increased Na delivery to the DCT, increasing aldosterone stimulation of the Na-K-ATPase, which acts to increase Na reabsorption in exhange for K and H secretion)*

Answer 64

**Fruit.** Mainly alkali load *CRF causes an acid load by ????*

Answer 65

**0.00004meq/L** *4 zeroes and then a 4*

Answer 66

**Diuretic use** Carbonic anhydrase inhibition -\> Hypokalaemic metabolic acidosis (due to incresased HCO3 loss in urin, and reduced H+ secretion -\> increased K+ excretion ) Chronic diarrhea -\> Hypokalaemic acidosis due to K and HCO3 loss in the stools

Answer 67

**e. Secondary active transport mechanism operates in distal tubule** *DCT H+ loss is due to an ATPase (stimulated by aldosterone)* * a. Acetazolamide decreases tubular secretion (by reducing the formation of H2CO3 in the lumen -\> increased HCO3 loss) * b. Aldosterone increases distal tubular secretion (see above) * c. Much more acid secretion occurs in proximal than distal tubule (due to Na-H exchanger) * d. Lowest tubular fluid pH achievable is 4.5 (hence buffering needed)