1. fenestrated endothelium - freely permeable to water, small solutes; have negatively charged glycogproteins that retard the filtration into Bowman's space of large anionic proteins

2. basement membrane - a charge-selectivity filter, a porous matrix of negatively-charged proteins/collagen

3. podocyte epithelium (visceral layer) - processes interdigitate to cover the basement membrane (separated by filtration slits); a size-selectivity filter

What factors determine UP?

How does this pressure gradient change as you move down the arteriole?

UP determines the net direction of filtration, and provides the driving force for ultrafiltration from the glomerulus into Bowman's space - the passive movement of an esentially protein-free fluid from the glomerular capillaries into Bowman's space

Hydrostatic pressure of the capillary (strongest factor, promotes filtration of fluid from the capillary lumen into Bowman's space

Oncotic pressure of the capillary and hydrostatic pressure in Bowman's capsule (oppose the formation of glomerular filtrate)

This gradient DECREASES as you move down from the afferent arteriolar end to the efferent arteriolar end. This is because capillary oncotic pressure increases as water diffuses into Bowman's space, and the protein concentration in the capillary increases.

What are the effects of each of the following on glomerular hydrostatic pressure (that is, the force promoting absorption/formation of glomerular filtrate), glomerular filtration rate, and renal blood flow?

Afferent arteriolar constriction

(MODERATE) Efferent arteriolar constriction

Afferent arteriolar dilation

Efferent arteriolar dilation

Which set of arterioles does the SNS have a greater effect on?

Angiotensin?

AA constriction: ↓P_GC, ↓GFR, ↓RBF

EA constriction: ↑P_GC, ↑GFR, ↓RBF

AA dilation: ↑ everything!

EA dilation: ↓P_GC, ↓GFR, ↑RBF

SNS constricts AA more than EA

Angiotensin constricts EA more than AA

I/c GFR --> I/c NaCl delivery to macula densa -->

I/c ATP and adenosine (transported by the extraglomerular mesangial cell) -->

Adenosine binds to receptors in smooth m cells surrounding the AA -->

Rise in intracellular [Ca⁺⁺] -->

vasoconstriction in AA, bringing GFR back down

Increased GFR -->

Increased NaCl delivery to loop of Henle -->

Signal generated by macula densa of juxtaglomerular mesangial cells -->

Constriction of EFFERENT arterioles -->

Blood pressure goes back down

Sympathetic innervation to the nephron

Where do sympathetic neurons synpase?

What happens when hypovolemia occurs?

smooth muscle - AA constriction

granular cells in AA - stimulate renin secretion

inc SNS -> renin -> angiotensin -> vasoconstriction, helps restore BP

Renal prostaglandins dampen vasoconstriction caused by AT-II and sympathetic activity - imp. to prevent ischemia

i/c SNS and plasma AT-II --> i/c renal PG synthesis & release

Why does inulin concentration in the proximal tubule increase 3 fold as filtrate moves down its length?

What other substances increase in concentration? Which ones decrease in concentration?

2/3 of water is reabsorbed, all of inulin is reabsorbed

Na++ reabsorption is identical to water, so its concentration is unchanged (same for K+)

PAH conc increases even more than inulin's

Urea and Cl- conc increase, but not as much as inulin and PAH

HCO3-, amino acid, and glucose conc all decrease (these are reabsorbed, especially glucose).

Where does Na+/K+ ATPase operate?

Why is it important?

At the basolateral membrane

It decreases the cellular conc of Na+, creating a gradient by which other substances (notably glucose) can cross the apical membrane. Glucose is reabsorbed, and this is how it happens.

Na+-glucose cotransport happens at the apical membrane, and glucose exits the basolateral membrane via facilitated diffusion.

Saturable processes

What is T_MG?

What is the normal range for blood glucose?

There are a limited number of Na+-glucose cotransporters in the luminal (apical) membrane

If glucose load (GFR x P_glucose) exceeds tubular glucose maximum (T_MG) --> glucosuria, e.g. diabetes

Same principles apply to amino acid transport and PAH

N blood glucose: 70-110 mg/dL

If PAH levels are low/normal, all of it will be excreted and it will approximate RPF. PAH only equals RPF if all the PAH is excreted from the plasma

Secretion of organic ANIONS in PCT: tertiary active transport

3 steps

1. Na-K ATPase sets up Na gradient

2. b/c Na is more conc outside the cell, Na can reenter the cell across the basolateral membrane and it brings alpha-ketoglutarate with it (recall alpha-KG is an intermediate of the Krebs cycle)

3. b/c a-KG is more conc inside the cell, now it can move out of cell across the basolateral membrane in exchange for organic anion (e.g. OA-, PAH)

=> PAH is brought into the cell "uphill," can be secreted across the luminal membrane and be excreted.

This is how PAH is completely cleared

1. Na-K ATPase sets up Na gradient

2. Na/H antiport across the luminal (apical) membrane brings Na in and H out. This sets up a pH gradient across the luminal membrane.

3. Some H+ come back in exchange for a cation (e.g. creatinine), which lowers the conc of that cation in the cell allowing more to enter across the basolateral membrane

Again, doesn't work unless Na+/K+ ATPase is working!

This is how creatinine is cleared - approximates GRF

Acid in the tubular lumen favors reabsorption of organic acids, but traps organic bases in the lumen

Give them acid!

To keep a base in the body, give them HCO3-