Ch6 Renal System
Kidney (overview)
- Input: renal artery
- Output: renal vein and ureter
- Functional unit: the nephron
Blood flow vs urine flow
Blood flow path
blood flows through:
- artery → afferent arteriole → glomerular capillary → efferent arteriole → peritubular capillary → vein
Urine formation path (high level)
- urine is generated at Bowman’s space, attached to the glomerular capillary via glomerular filtration
-
then:
-
tubular secretion moves substances from peritubular capillary → tubule
- tubular reabsorption moves substances from tubule → capillary
- remaining becomes urinary excretion
Nephron anatomy by location
- glomerulus and Bowman’s capsule: cortex
- proximal tubule: cortex
- descending loop of Henle: cortex → medulla
- ascending loop of Henle: medulla → cortex
- distal tubule: from ascending loop of Henle to medullary collecting duct (cortex)
Key orientation:
- cortex = outside
- medulla = inside
- urine ultimately goes to the ureter → urinary bladder
Glomerular Filtration
- pressure pushes water, salts, glucose, and urea out
- no cells and no proteins
Proximal Tubule Reabsorption
Orientation
- lumen faces the tubular epithelial cell (apical side)
- basolateral side of the tubular epithelial cell faces the peritubular capillary
Key note:
- all glucose is reabsorbed here
Transporters/channels in tubular epithelial cells
- Na\(^+\)/K\(^+\) ATPase (neither)
- SGLT1 and SGLT2 (apical): secondary active transport (cotransport with Na\(^+\) concentration gradient)
- Cl\(^-\) channel (apical and basolateral)
- AQP1 water channel (apical and basolateral): osmosis
- GLUT1 and GLUT2 (basolateral): diffusion
Net movement :
- glucose, Cl\(^-\), and water move from tubule → interstitial space
Descending limb of the loop of Henle
Transporters/channels :
- Na\(^+\)/K\(^+\) ATPase (neither)
- AQP1 (apical and basolateral): osmosis
Net movement :
- water moves from tubule → interstitial space (high salt concentration)
Ascending limb of the loop of Henle
Transporters/channels :
- Na\(^+\)/K\(^+\) ATPase (neither)
- NKCC2 (apical): transports Na\(^+\), K\(^+\), Cl\(^-\) into the cell
- K\(^+\) channel (apical)
- Cl\(^-\) channel (basolateral)
Net movement :
- Na\(^+\), K\(^+\) (less than Na\(^+\)) flow from tubule → apical
- Cl\(^-\) flows from tubule → interstitial space
Functional consequence :
- this makes the interstitial space high salt concentration for the descending limb of the loop of Henle
Distal (convoluted) tubule
Key features:
- sensitivity to hormones
Transporters/channels :
- Na\(^+\)/K\(^+\) ATPase (neither)
- ENaC (epithelial Na\(^+\) channel) (apical)
- Cl\(^-\) channel (basolateral and apical)
Net movement :
- Na\(^+\) and Cl\(^-\) flow from tubule → interstitial space
Medullary collecting duct (in medulla)
Transporters/channels :
- Na\(^+\)/K\(^+\) ATPase (neither)
- AQP2 water channel (apical)
- AQP3 and AQP4 water channels (basolateral)
Net movement :
- water moves from tubule → interstitial space (high salt concentration)
Vasopressin / Antidiuretic Hormone (ADH)
Mechanism :
- ADH binds to vasopressin receptor (GPCR) → activates cAMP → PKA → exocytosis of AQP2
- increases AQP2 expression on apical membrane
- increases water reabsorption
Negative feedback loop (ADH)
- sensor: osmoreceptor neurons in the hypothalamus (fire more if dehydrated)
- controller: neuronal network in hypothalamus
- actuating signal: ADH (vasopressin) released by posterior pituitary
- effectors: AQP2 expression level in medullary collecting duct
- controlled variable: osmolarity of interstitial space in hypothalamus
Diabetes insipidus
- neurogenic: loss-of-function mutation affecting hypothalamus
- nephrogenic: mutation affecting collecting duct cells
Macula Densa and Juxtaglomerular apparatus (salt sensing)
Key structures
- macula densa: senses salt content; located at the end of the ascending limb of the loop of Henle and the beginning of distal tubule
- juxtaglomerular cells: cells close to macula densa on the afferent arteriole
Feedback
- macula densa senses low salt content and triggers a feedback loop to increase salt reabsorption
Roles :
- controller and sensor: macula densa (releases prostaglandin when low tubular salt level)
Signaling cascade
-
actuating signals:
-
prostaglandin (PG)
- juxtaglomerular cells release renin
- angiotensin I (cleaved from angiotensinogen secreted from liver by renin)
- angiotensin II (modified by ACE in endothelium from angiotensin I)
- adrenal cortex releases aldosterone
Target and controlled variable
- effector: epithelial cells lining distal tubule and cortical collecting duct
- controlled variable: salt content at the beginning of the distal tubule
Aldosterone effect
When aldosterone binds:
- increases transcription of Na\(^+\)/K\(^+\) ATPase and ENaC