Week 12 Flashcards
Tubular reabsorption
- The kidneys control reabsorption of each substance separately to regulate excretion
- Transport occurs across tubular epithelium into interstitial space then across peritubular capillaries into blood
Paracellular path of reabsorption
Path between cells
Transcellular path of reabsorption
Path through cells
Reabsorption transport mechanism for sodium
- Primary active transport through ATPase
- Some through leaky junctions
Why does the bulk flow in the peritubular capillaries favor reabsorption
- Much lower capillary pressure because its the second capillary bed
- Interstitial pressure higher because tubule pushing out
Reabsorption in the proximal tubule
- Majority of filtered sodium, chloride and water reabsorbed
- High transport capacity due to brush boarder, transport proteins and mitochondria, and cell junctions are leaky
- High water permeability allows osmosis to keep pace with sodium and chloride
- Nutrients and bicarbonate rapidly absorbed
- Secretion of organic acids and bases occurs
Proximal Tubule Transport Mechanisms for amino acids and glucose
- Sodium-glucose co-transporter (SGLT): Uses Na to pull glucose into cell through secondary active transport against concentration gradient - amino acids transported into tubular cells
- Amino acids transfuse out of cell
- Glucose transporter (GLUT) transports glucose out of cell
Proximal tubule transport mechanisms for calcium
- Moved through paracellular pathway pulled by water moving by osmosis causing solutes to be pulled through bulk flow
- move down gradient into cell and then uses primary active transport to transport out of the cell
Solute and water transport in the loop of henle
- Descending segment is highly permeable to H2O, but does not transport ions
- Ascending segments are H2O impermeable, but thick segment actively reabsorbs ions (25% of filtered Na and Cl)
Transport in distal tubule and cortical collecting duct
- early distal tubule is similar to thick ascending loop (reabsorbs 5% of filtered Na and Cl)
- Late distal tubule and cortical collecting duct have similar characteristics - reabsorb Na and secrete K and secrete or reabsorb H+, HCO3- and K+
What are the two distinct cell types that the late distal tubule and cortical collecting duct are composed of and what are their functions?
Principle Cells: reabsorb Na+ and secrete K+
Intercalated Cells: secrete or reabsorb H+, HCO3- and K+
Secretion Mechanisms in intercalated cells
Two types with opposite functions, which are regulated based on K+ needs and pH homeostasis
Type A:
- Secrete H+ and reabsorb K+
- CO2 flows into cell and reacts with water, HCO3- is reabsorbed using secondary transport with Cl- and H+ is secreted using active transport
- Cl- excreted through diffusion
Type B:
- Secrete K+ and Bicarbonate
- Opposite direction of mechanisms occurs
Medullary Collecting Duct
- Reabsorbs 5% of filtered water, sodium and chloride
- Water permeability is regulated to determine the final urine volume and concentration
- Some urea is reabsorbed into the interstitium via urea transporters to help raise the osmolarity of the medulla
Glomerulotubular Balance
The proximal tubule and think ascending loop of Henle have intrinsic ability to increase reabsorption in response to increases in glomerular filtration rate (partially in response to mechanical forces on tubule)
Aldosterone (Site of action and effect)
- Collecting tubule and duct
- NaCl, H2O reabsorption, K+ secretion and H+ secretion
Angiotension II (Site of action and effect)
- Proximal tubule, thick ascending loop of henle, distal tubule and collecting tubule
- NaCl and H2O reabsorption, H+ secrretion
- Activates NHE causing secondary transport of Na by moving H+ out of cell, uses active transport to move into interstitial fluid
Antidiuretic Hormone (Site of action and effect)
- Distal tubule/collecting tubule and duct
- H2O reabsorption
- Aquaporin II activation
Atrial natriuretic Peptide (Site of action and effect)
- Distal tubule/collecting tubule and duct
- less NaCl reabsorption
Parathyroid Hormone (Site of action and effect)
- Proximal tubule, thick ascending loop of henle, distal tubule
- less PO4- reabsorption nad more Ca++ reabsorption
How does loss of functional nephrons affect renal excretion of water and solutes?
- Feedback mechanism compensates and upregulates function of remaining nephrons
- 90-95% loss and still maintain Na levels - regulated primarily by reabsorption
- only need to loss 25% to see an increase in waste products - impaired filtration
Osmolarity homeostatic loop
Sensor: Osmoreceptor (Hypothalamus)
Control Center: Brain (Hypothalamus)
Signal to effector: ADH
Effectors: Kidneys, thirst (water input)
Osmoreceptor-ADH Feedback System
- Specialized neurons in the anterior hypothalamus act as osmoreceptors in the homeostatic regulation of extracellular osmolarity
- Hypertonic conditions lead to shrinkage of osmoreceptor cells, leading to increased frequency of AP
- Osmoreceptors synapse with integrating neurons in the supraoptic and paraventricular nuclei, which project axons to the posterior pituitary
- When activated, these integrating neurons release ADH into the circulation to favor water reabsorption
- Baroreceptors also synapse with the integrating neurons in the supraoptic and paraventricular nuclei, sensing decreases in blood pressure as a result of decreased blood volume
Does the osmoreceptor-ADH feedback loop respond more to changes in osmolarity or blood pressure
Much greater release of ADH with changes in osmolarity
Countercurrent Multiplier Mechanism
- As fluid moves through loop, Ions are pumped out of the ALoH into interstitium, increasing its osmolarity
- water diffuses out of the DLoH making it more concentrated
- fluid continues to flow forward
- Steps 1 and 2 are repeated
Constant flow of lower concentrated filtrate out and higher concentrated filtrate in increases the concentration of the filtrate to a max, allowing for highly concentrated urine
What two factors create hyperosmotic medullary interstitium?
- Active transport of ions out of the thick ascending loop of Henle
- Low water permeability of the descending loop of Henle
How does ADH levels affect water permeability and urine concentration?
WHEN ADH LEVELS ARE LOW
- Permeability of distal tubule and collecting duct is low
- High volumes of diluted urine produced
WHEN ADH LEVELS ARE HIGH
- water permeability increases and reabsorption is high - more in cortical collecting duct where largest osmotic gradient exists
- low volumes of concentrated urine is produced
How does ADH act to increase water reabsorption (physiologically)
- ADH binds to tubular cell
- activates cAMP which acts on protien kinase leading to protien phosphorylation
- Activates intracellular vesicles to move to membrane, increasing concentration of aquaporin-2 on membrane and facilitating movement of water
ADH effect on urea concentration
- Tubule normally has low permeability to urea
- ADH activates urea transporters in the inner medullary collecting ducts, enabling urea diffusion into medullary interstitium
- Urea diffuses back into the tubule in earlier regions where its concentration is lower
- This increases osmolarity and amplifies water reabsorption
How is the medulla kept hyperosmotic? why isn’t the solute simply carried away in the blood, since there is a net absorption of fluid from interstitium into peritubular capillaries?
- Capillaries follow same path
- Constant equilibrium with extracellular fluid
Osmoreceptors Control of Thirst
- Hypothalamus contains osmoreceptors that control thirst (Thirst Centre)
- Stimuli that increase water reabsorption in the kidneys will also stimulate thirst
- Other stimuli, like a dry mouth, will also stimulate thirst without effecting ADH and reabsorption
