MT 4 - Kidney

Question 1

40. Basic physiological functions of the kidney: filtration

Answer 1

• Determined by effective filtration pressure (EFP) and the permeability of the barriers
• EFP: Depends on ratio of hydrostatic blood and tissue-P, and colloid osmotic Ps.
• Hydrostatic P of the glomerulus (GP)
• Bowman-sheath’s P (CP)
• Colloid-osmotic P of the plasma (GCP)
• EFP = GP – (CP + GCP)
• Capillary filtration coefficient (CFC)
• The degree of ultrafiltration in glomerulus is 100x higher than any other capillary areas.
• Most important factor: lamina densa of the basal membrane. Neg charged= strongly reflects the proteins.
• Total filtration: 180-200 liter/100 kg btw/day

Question 2

40. Basic physiological functions of the kidney: Secretion

Answer 2

• Some substances are secreted after filtration and reabsorption, others directly from the blood vessel.
• From the plasma leaving the glomerulus through the efferent arteriole further substances can get into the tubular lumen at the site of the peritubular capillaries.
• Both transcellular and paracellular.

Question 3

40. Basic physiological functions of the kidney: Excretion

Answer 3

• As a result of the filtration, reabs. and secretion by the end of the tubular system the secondary filtrate of urine is formed.
• Rate of excretion = the urine or selected material excreted.
• Average excretion rate of urine is 2-3 ml/min/100 kg bodyweight

Question 4

40. Basic physiological functions of the kidney: Reabsorption

Answer 4

• The extremely large filtration rate could mean a fatal loss of fluid, if it appeared in full amount in the urine.
• More than 90% of the filtrated amount is reabsorbed
• Two main pathways: paracellular and transcellular.

Question 5

41. Glomerular filtration rate (GFR)

Answer 5

• The amount of filtrate prod. per unit time by all of the nephrones of the two kidneys.
• Measured with inulin (polyfructose) or endogenous creatinine
• The clearance value of inulin and creatinine is 120 ml/min/100 kg bwt.
• Autoregulation: Constant even under wider periopheral arterial mid-P changes.
• Myogenic mechanism+tubulo-glomerular feedback
• Tubulo-glomerular feedback: The macula densa of the juxtaglomerular apparatus senses the V-changes of the distal tubule and its probably secreted signals to adjust the GFR.

Question 6

41. Extraction

Answer 6

• The ability of the kidney to elim. a subs. from the organism.
• In the renal a. a certain amount of subs. in a certain conc. arrives at the kidney, and the same or red. amount leaves through the vein.
• Max.: if the subs. entering on the a. side does not appear at all on the v. side (E=1).
• Min.: if the entire amount of the subs. appears on the v. side and nothing gets into urine (E=0).
• E=Pa–Pv/Pa (Pa=arterial conc. Pv=venous conc.)

Question 7

41. Clearance

Answer 7

-A measure of the V of plasma completely freed of a given subst. per unit time by the kidney
-Kidneys ability to remove a subst. from the blood plasma and forward it to urine
-All filtered subst. has a clearance value
-Certain subst. are exclusively filtered (neither absorbed nor secreted, e.g. inulin). Their clearance is equal to the rate of GFR
-Other subst. are entirely secreted (para-amino-hyppuric-acid). The clearance of these gives the renal plasma flow (RPF).
Clearance of:
1.PAH: Constant at low plasma conc. At higher conc. the secretory capacity of the tubules decr., and the tubular cells become unable to secrete more PAH->its clearance decr..
2.Inulin: A substance that is typically only filtered
-Due to this, its conc. in the plasma does not influence its clearance even under extremely high values.
3.Urea: freely filtered, and then passively moves among those parts of each tubule section, which are permeable for urea.
4.Glucose: freely filtered, but under normal proximal tubular activity, glu doesn’t get into the desc. limb of Henle-loop. It is entirely reabsorbed in the proximal tubule. Under norm. glu plasma conc.; clearance is 0.

Question 8

42. Renal plasma flow (RPF)

Answer 8

• V of blood plasma delivered to kidneys per unit time
• Determination based on Flick-principle: The amount of subst. entering the kidney on arterial side per unit time, must be equal to the sum of subs. leaving kidney with renal vein and with urine.
• Measures the clearance of any subst. that is both filtered and completely excreted - such that none remains in the outgoing renal vein, can be used to determine the RPF
• RFP=(UxV)/(Pa-Pv) (Pa=arterial conc. Pv=venous conc., U=subst. conc. in urine, V=rate of urine prod.)

Question 9

42. Filtration fraction

Answer 9

• FF=GFR/RPF.
• RPF and GFR don’t change within wide ranges of BP.
• Regulated by adaptive contraction of the efferent arteriole, and tubulo-glomerular feedback.
• Myogenic mechanism:
  1) To incr. BP: vasoconstriction in afferent arteriole
  2) The decr. BP: vaso-dilation in afferent arteriole, vasoconstriction in efferent arteriole

Question 10

43. Transport processes in the proximal tubule

Answer 10

-70% of the filtrate is reabsorbed in the prox. tubule; the hormonal regulation is not significant.
-Reabsorption takes place in two phases:
1)Actively to the interstitium
2)Passively to the peritubular capillaries
•Glucose, aa. and Na will be pumped out of the tubules by active transport.
•Chloride will follow Na to the peritubular space
•Water will move to peritubular space because of osmosis
•Some compounds because of high conc. in the filtrate but low in blood can move through diffusion.
-Na+: Na+/K+ - ATPase pump
-H+: The Na+ entry results in H+ secretion. Inhib. by amiloride.
-HCO3-: Cell is impermeable to HCO3-. CO2 diffusing into the cell rapidly, transforms into H+ and HCO3- with help of IC carbonic anhydrase->indirect HCO3- transport
-Cl-: Transcellular. Cl-acidic anion antiporter protein transports Cl to the cell, and acidic anion from cell to lumen.
-H2O: as a result of incr. peritubular oncotic P, it paracellularly migrates from lumen to interstitium. Facilitated by aquaporin-1.
-Glu, aa: 100% withdrawn from proximal tubule together with Na+, via sec. active symport, maintained by the Na+/K+-ATPase pump. Own specific carriers.
-Urea: Approximately half are passively resorbed through cells and paracellular pathways, the rest stays in interstitium and contributes to form. of special osmotic layering in kidney

Question 11

44. Transport in the loop of Henle

Answer 11

• Reabs. 30% of filtrating Na
• TDL: little secretory and abs. ability. No significant active transport in either direction. High permeability.
• TAL: reabs. 25% of the filtered amount. Main force is Na+/K+-ATPase pump; pumps Na from cell to interstitium, and K from interstitium to cell.
• On luminal side Na+ can be reabs. due to decr. IC Na+.
• Excess K leaves passively via K+chs of basolateral side.
• Impermeable to water->lumen becomes hypoosmotic
• Symporter prot. inhib. by furosemide->water and salt loss ->diuresis occurs
• Furosamide: Inhibitor of the Na+/K+/Cl- reabs.

Question 12

44. Transport in the distal tubule

Answer 12

•Regulates pH by abs.bicarbonateand secretingH+ into the filtrate, or opposite
•Na and K levels are controlled by secreting K+and absorbing Na+.
•Calciumregulation by reabs. Ca2+in response to parathyroid hormone.
-Na+/Cl- symport proteins
-Cl carried by K+/Cl- cotransporter proteins into interstitium
-Hormonal and pharmacological effects:
*PTH: Ca2+ reabs., calcitonin: Ca2+ excretion, both: phosphate excretion
*Carbonic anhydrase inhibitors (acetasolamide)
*Thiazide: Inhibitor of Na+/Cl- symport

Question 13

45. Transport in the distal connective tubule and the collecting tubule

Answer 13

• Where form. of the hormonally regulated final urine takes place.
  1) CNT, CCT=mineralcorticoid dependent Na+ reabs.
  2) CCT=ADH-dependent water reabs.
  3) MCT=ADH-dependent water and urea reabs., ANP-dependent Na+ excretion
• Main and intercalary cells: regulation of acid/base and K-balance.
  1) Mineralcorticoid dependent Na+/K+ transport
  2) Active water transport
  3) Acid-base balance
  4) K+ transport

Question 14

45. Transport in the distal connective tubule and the collecting tubule: 1) Mineralcorticoid dependent Na+/K+ transport

Answer 14

• Basolateral Na/K pump and luminal Na- and K-chs.
• Appearance of these proteins is primarily aldosterone dependent. Na+-chs can be inhib. by amiloride.
• Transport of K is passive in both directions: luminal (secretion) and basolateral (reabsorption).
• If K is in excess, z. glomerulosa prod. more aldosterone, and more luminal Na+ and K+-chs are expressed

Question 15

45. Transport in the distal connective tubule and the collecting tubule: 2) Active water transport

Answer 15

• Flow of water bw. renal tubules and interstitium is directed by osmotic forces
• Water moves paracellularly
• Hormonally regulated
• Linked to aquaporin-2
• ADH from surface of the microsomes, affects AQP-2 to get to luminal surface, and facilitates reabs. of water

Question 16

45. Transport in the distal connective tubule and the collecting tubule: 3) Acid-base balance

Answer 16

• CCT and CNT most important for acid/base balance
• In intercalar cells:
• K secretion (H-pump) and HCO3 reabs.
• In case of alkalosis: HCO3 prod. and secretion
  a) Defence agains acidosis
• H+ of water of the cell is forwarded to lumen by electrogenic luminal H+ pump
• Carbonic anhydrase unites CO2 with the OH group.
• The formed HCO3- is carried to blood by Cl-/HCO3-antiporter. Cl- leaves through a passive channel
  b) Defence against alkalosis
• H+ originating from dissociation of water on basolateral side is removed by H+/K+ ATPase pump to interstitium.
• HCO3-/Cl- antiporter on luminal side removes HCO3- from cell into lumen
• Excess K accumulated in the cell through a passive K+ channel gets back to interstitium.

Question 17

45. Transport in the distal connective tubule and the collecting tubule: 4) K+ transport

Answer 17

• K+ conc. of plasma is regulated very precisely, as its conc. change affects all irritable tissues
• The 0,1% incr. of plasma K level provokes aldosterone secretion, which stimulates K secretion into distal tubule
• In CNT, CCT: CCT principal cells: reabs. of Na and mineralcorticoid dependent secretion of K.
• CCT intercalary cells: reabs. with H+/K+ exchange.

Question 18

46. Osmoregulation in the kidney

Answer 18

• Maintain osmotic homeostasis
• Important because a shift in the osmotic environment may destroy life important physiological processes.
• When salt deficiency, salt excess, shortage of water, excess of water occurs, at first the shifted osmotic balance is restored to normal: feedback within a couple of minutes.
  1) Hyperosmosis
  2) EC and IC getting osmotic equalized (minutes): hyperosmotic isovolaemia
  3) Hypothalamic osmoreceptor activity incr.
  4) Blood ADH level incr.
  5) Distal tubule: AQP-2 expression incr.
  6) Free water clearance decr., water retention
  7) Isosmotic hypervolemia
• Hyposmosis: In case of red. salt intake or primary salt loss the osmotic conc. of EC decr.:
  1) The prim. hyposmosis inhib. the ADH prod. and release.
  2) Free water and clearance incr., and then hypovolemic isosmosis develops.
  3) By long term regulatory mechanisms it is turned back to the direction of isosmotic isovolemia.
• ADH-mechanism: maintain isoosmosis. Resets H2O permeability.

Question 19

46. Osmoregulation in the kidney: The countercurrent system

Answer 19

• Maintenance of isosmosis and isovolemia requires that urine V and urine osmolality change in a wide range
• Expands energy to create a conc. gradient
• Henle´s loop: desc. limb is only water permeable, asc. limb is water impermeable ->incr. osmotic gradient
• Reabs. of Na+/K+/Cl- of TAL -> red. osmolarity of lumen
• Can´t be followed by water migration since TAL is impermeable to water
• The rising interstitial osmotic conc. at TAL attracts water from desc. limb (permeable to water)->osmolarity incr. inside lumen

Question 20

47. The maintenance of isoismosis

Answer 20

• When blood volume is reduced as a result of decreased fluid intake or injury, the body gets dehydrated.
  1. Concentration of salts dissolved in the blood increases, causing a rise in osmotic pressure.
  2. Receptors in the hypothalamus react to the shift in osmotic pressure and trigger the posterior lobe of the pituitary to activate release of ADH.
  3. At the same time, the thirst center in the hypothalamus responds by stimulating the sensation of thirst (H2O intake). Adequate stimulus is the EC hyperosmosis.

Question 21

47. The maintenance of isoismosis, the ADH mechanism

Answer 21

• Level of action: distal connecting tubule & collecting duct
• Result: resets H2O permeability
• Hyperosmosis:
  1. Hyperosmosis
  2. EC and IC getting balanced (min) -> hyperosmostic isovolemia
  3. Hypothalamic osmoreceptor activity increases
  4. Blood ADH level increases
  5. Distal tubule: AQP-2 expression increases
  6. Free water clearance decreases, water retention
  7. Isosmotic hypervolemia
• Hypoosmosis: ADH inhibiton (no water rentention) -> isosmotic hypovolemia

Question 22

48. The maintainance of isovolemia

Answer 22

• V regulation: balance of NaCl uptake and excretion
• Extra salt load: Elim. takes 1-2d; the hyperosmosis turns on Verney-mechanism (sensation of thirst->drinking->isosmosis)
• Isosmosis is reset within 1-2h, but extra salt and water stay in EC space. EC space is extended, resulting in hypervolaemia.
• Effects of extra V of water on circ.:
• Blood V incr., arterial P incr., baroreceptors stimulated
• *esults in peripheric vasodilation and a decr. of oncotic P due to hemodilution, and therefore fluid leaves the circ. towards interstitium

Question 23

48. Renin Angiotensin System (RAS)

Answer 23

• Hormonal system regulating plasma Na-conc. and arterial BP
• Effects:
  1. Renin: no direct effect
  2. Angiotensin I: no direct effect, precursor
  3. Angitensin II: Pressor effect, incr. the peripheral resistance:
• Direct salt retention, renal venal constriction, RBF/GFR decr.
• Indirect salt retention, most important stimulator of aldosterone secretion->salt retention.
• Nervous system:
• *Incr. arterial P by stimulating 4th ventricle
• *Dypsogenic (incr. thirst, water uptake)
• *Incr. peripheral catecholamine synth.
• *RBF/GFR decr. but autoregulation will correct it.
• *ADH stimulation
  4. Angiotensin III: Pressor effect 50% lower than angiotensin II stimulation of aldosterone secretion

Question 24

48. Aldosterone

Answer 24

• Most important of mineralocorticoids, steroid hormone.
• Prod. by zona glomerulosa cells of adrenal cortex.
• Key E: 18-aldolase; present only in this layer.
• Main: Na+ reabs. and K+ excretion, essential in the retention of Na and water.
• Prim. stimulus of secretion is incr. of K conc. of the blood, the defense against hyperkalemia.
• The single regulator of the K+ excretion, and one factor of Na+ reabs.
• ADH plays primary role in setting the plasma osmolality, while aldosterone regulates the entire Na content of the body as a member of the RAS system.
• Main site of aldosterone effect is distal tubule and cortical section of the connecting and collecting ducts.

Question 25

49. The process of urination

Answer 25

• Urine is prod. continuously in kidney
• Emptying: periodical process
• Rhythmical contraction of calyx forwards urine into the renal pelvis
• In case of incr. urine formation, the proc. becomes continuously.
• Peristalsis of ureter forwards urine with a speed of 2-3 cm/s.
• Under normal urine speed the wall of ureter is shrunk, collapsed, and only periodically opens–one “bolus” at a time is forwarded to the bladder.
• No urinal reflux in normal case
• Bladder wall: consists of special SM elements and elastic fibers; react to stretch by relaxation.
• During filling: tension of bladder wall incr. only gradually and mechanoreceptors are only slightly stimulated
• At a certain point of filling, activity of mechanoreceptors suddenly incr.->urination is induced

Question 26

49. The process of urination: regulation

Answer 26

• Emptying of bladder controlled by urinary center in pons, based on info. arriving from mechanoreceptors
• Lumbal (sympathetic), sacral (parasympathetic), and appropriate somatic motor center (abd mm., perineum, outer sphincter).
  1) Saturational:
• During filling PS activity responsible for contraction of bladder wall (m.detrusor) is presynaptically inhib. by the continuous sympathetic activity.
• The same sympathetic basic tone (beta2 receptor) relaxes detrusor mm. and contracts via alpha1 receptors of SMs of bladder neck.
  2) At urination
• Incr. mechanoreceptor activity during urination affects the center, which incr. parasympathetic activation and inhib. somatic and sympathetic activity: bladder wall contracts, sphincters relax->urination begins.
• The center is connected to cortex and hypothalamus, which can exert a certain inhib. on its activity: retention of urine can be achieved under certain bladder tension, earlier causing urination.