MT 4 - Kidney Flashcards
- Basic physiological functions of the kidney: filtration
- 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
- Basic physiological functions of the kidney: Secretion
- 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.
- Basic physiological functions of the kidney: Excretion
- 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
- Basic physiological functions of the kidney: Reabsorption
- 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.
- Glomerular filtration rate (GFR)
- 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.
- Extraction
- 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.)
- Clearance
-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.
- Renal plasma flow (RPF)
- 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.)
- Filtration fraction
- 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
- Transport processes in the proximal tubule
-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
- Transport in the loop of Henle
- 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.
- Transport in the distal tubule
•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
- Transport in the distal connective tubule and the collecting tubule
- 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
- Transport in the distal connective tubule and the collecting tubule: 1) Mineralcorticoid dependent Na+/K+ transport
- 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
- Transport in the distal connective tubule and the collecting tubule: 2) Active water transport
- 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