Flashcards in Renal 3 Deck (11)
How is the GFR regulated?
- To protect the glomerulus, better to modify before the glomerulus (afferent arteriole) (regulating GFR)
- Large pressure in glomerulus : damage filtration barrier (barotrauma)
Renal blood flow
Glomerular filtration rate
As artieral pressure increases (between 60-130, we don't have any change in blood delivery to kidney or rate of filtration)
- Bp is doubling, but blood delivered and filtered by kidney is the same (in that range)
Augoregulatory mechanisms to protect glomerulus (GFR) -intrinsic regulation
- Myogenic response (BP increases, reflexive vasoconstriction, rapid)
- Tubuloglomerular feedback: communication between nephron. Modifies pressue via distal feedback. Prevents large sudden pressure increases.
Extrinsic (outside the kidney)
- Hormones (modify amount of filtration that occurs)
- Neural (sympathetic neurons)
- Regulate filtration that occurs.
Green line: urine output *
Changes in blood pressure, see increase in urine output
Describe the myogenic response?
Rapid autoregulatory response for protecting glom
- TOP: transmural pressure. Increase in pressure across arterial wall - BP increase
- Middle: concentration of calcium
- Bottom: diameter of the vessel
- Stretched at first
- But vasoconstricted over time!
Myogenic response: rapid, response to increase in pressure
- Wall of afferent arteriole will stretch
- Increase transmural pressure.
- Channels will activate and depolarize membrane
- Active ca2+ channels (found on membrane)
- Calcium release from calcium stores (SR, influx)
- Vasoconstriction, activation of myosin light chain to form cross bridges
- 50% of our autoregulation that we see is cause of this!
describe the tubuloglomerular feedback? and some common things for both mechansims of GFR regulation
Tubuloglomerular Feedback (TGF)
RA: resistance of afferent arteriole.
- Diameter is decreased, resistance flow will increase.
- Increase in arterial pressure
- Increase in renal blood flow and pressure in capillary
- Myogenic response reduces this, but still somewhat increase
- Increase in GFR.
- Increased tubular flow (increased na and c+)
- Macula densa, top of loop of henle and distal convoluted tube. (greater sodium and cholride reabsorption at that region.
- Release effector mechanisms, things act on smooth muscle of afferent arteriole.
- Vasoconstriction of afferent arteriole.
Increase in arterial pressure = decrease diameter of afferent arteriole, cause vasoconstriction. Protects glomerulus.
- Reduced renal bloodflow and reduced pressure within capillaries
- GFR back down to normal
- KEEP GFR STABLE OVER 60-130 ML MERCURY
what are extrinsic factor regulation of GFR
Use horomnes and innervation to do FINE regulation
Neurons: onto afferent or efferent arterioles.
Reduce blood flow and GFR by altering vasuclar tone and vasocontrciting.
Act on intraglomerullar mesangial cells.
- Found within bowman's space
- Close to filtration barrier
- Beside podocytes.
- Can contract/relax in response to glom.
- Change surface area for filtration to occur.
Change filtration barrier to modify amount of filtration possible.
What are different routes of transport?
Passive: moving down electrochemical gradients
- Facilitated diffusion (pore, channel, carrier protein)
- Primary: use ATP to power it , sodium potassium ATPase
- Secondary: couple transport something down its gradient to power something up its gradient (sodium going in helps calcium get out)
- Moving AGAINST gradient
- TRANScellular: across cells
- Paracellular: between cells
Permeability of tight junctions DECREASES as you move towards collecting duct.
Describe renal epithelial cells.
- Apical surface of tight junction will isolate it from the basal membrane
○ Keeps proteins to their separate sides (apical/basolateral)
- Neuron differences
- INside is negative relative to outside (0)
- Potential differences between peritubular spaces.
- Space on basolateral side and tubular lumen.
○ Peritubluar space is zero (standard)
○ Negative potential within tublar lumen, neutral, or positive. Depending where you are, this transepithelial potential CHANGES.
Brush border on epithelial sides? Helps with transport *** check slides
Describe the overview of na reabsorption.
- Filtered load: amount of sodium gets filtered into ultrafiltrate per day (plasma sodium concentration x GFR)
- Fractional reabsorption: as you go along the nephron, what fraction of sodium has been reabsorbed into blood. (sodium remaining in tubule divided by initial amount)
○ Sodium is freely filtered, so concentration in ultrafiltrate should be the same as in plasma)
○ 1 - that radio = amount of sodium reabsorbed. (67%, that specific section)
○ Adds to fractional reabsorption
- Fractional excretion: amount of sodium that is excreted. Sodium in urine and flow of urine / GFR, should be pretty LOW. 0.4 %
LOTS OF SODIUM ABSORBED (BULK) IN PROXIMAL SEGMENT (2/3 IN THE 1ST SEGMENT)
(FINE) REGULATION OF SODIUM REABSORPTION HAPPENS IN COLLECTING DUCT REGION (modified)
what determines reabsorption in different areas?
Sodium potassium pumps: important for establishing gradient of sodium, helps with secondary transport on apical side
1. Different transporters available, amount of transport
2. Changes in regional permeability (i.e. descending thin limb is impermeable to sodium, no ATPase)
3. Composition of the fluid in the tubule
Fluid changes as it goes through the tubule.
4. Voltage gradient in transepithelial
Slight postive lumen favors transport into tubule in some regions
describe proximal tubule reabsorption 1.
Proximal tubule Na reabsorption
- Bulk sodium reabsorption
- Sodium proton exchanger (NHE3)
- Bicarbonate NBC1 transporter
1. Establish gradient with sodium potassium atpase
2. Electrical gradient for sodium to move in (intracelluar is negative)
3. Sodium proton exhanger brings sodium down and takes proton out into tubular lumen
4. Gets sodium across apical membrane.
5. THEN sodium bicarbonate cotransporter, takes it up gradient by moving bicarbonate down its concentration gradient across basal side. NOT atp reliant.
NET reabsorption (from tubule into blood)
- Also reclaim some bicarbonate
nBC1: recalims the bicarbonate.
describe proximal tubule na reabsorption 2 (coupled with OTHER solutes)
Solutes: glucose, phosphates, amino acids, paired with movement of sodium.
Glucose carried across the cell.
Comes in against glucose gradient, carried out of the cell on the basolateral side.
Don't wanna lose glucose!
- Not wasted in excretion, want it back!
- Electrogenic effect: net movememnt of positive charge into the cell, tubular lumen comes slightly negative (no more protons going out to counteract it)
- Slightly negative tubular lumen because of this.