Notes

Glomerular Filtration and Renal Clearance:
Urine formation begins with filtration of plasma from capillaries into Bowman's space, deemed glomerular filtration. Glomerular capillaries are lined with podocytes. Selectivity of filtration determined by molecular size of intravascular components and electrical charge of filtration components.

Glomerular filtration barrier determines the composition of the ultrafiltrate:
- Capillary endothelium: fenestrate, filled with negatively charged glycoprotein and podocalyxin.
- Basement membrane: collagen, proteoglycans, and glycoproteins
- Filtration slits of 25-65nm packed with negative proteins sit inside podocytes.
Composition of ultrafiltrate: most ions and low molecular weight proteins (< 7 Da) are freely filtered. Almost total exclusion of large plasma proteins like albumin, ions attached to proteins excluded as well. Negatively charged macromolecules are filtered to a less extent and positively charged ones to a greater extent.

GFR = Kf x NFP. Kf = filtration coefficient --> glomerular capillary permeability and total glomerular capillary surface area. NFP = net filtration pressure
Filtered load: total amount of a substance freely filtered into bowman's capsule from the renal glomerular capillaries. Filtered load can be calculated by filtered substance X = GFR x [X] in the plasma. If a quantity of a substance excreted in the urine is less than the filtered load, tubular reabsorption must have occurred. If quantity of a substance excreted in the urine is greater than the filtered load, tubular secretion must have occurred.

Control of GFR: Constrict and dilation of AA and EA are major players in altering GFR.
- AA constriction --> decrease in GFR, RBF, and hydrostatic pressure in capillaries
- EA constriction --> increase in GFR and hydrostatic pressure, decrease in RBF
- AA dilation --> increase in GFR,RBF, and hydrostatic pressure
- EA dilation --> decrease in GFR and hydrostatic pressure, increase in RBF

GFR strongly influences excretion of salt and water. Rise in BP causes increased excretion of water and salt.

Kidneys regulate their blood flow by adjusting vascular resistance, keeping RBF and GFR constant as arterial pressure rises between 90 and 180mmHg. There are mechanisms responsible for regulation of RBF and GFR
- Myogenic mechanism: vascular smooth muscle tends to contract when stretched, very fast acting; protects from short-term fluctuations in blood pressure.
- Tubuloglomerular feedback: macula densa cell act as salt censors, sense NaCl in tubular fluid. High levels of Na+ past the macula densa cause a decrease in GFR (afferent arteriole constriction.

Myogenic mechanism:
- When BP increases across the afferent arteriole, the smooth muscle membrane is stretched activating Ca2+ and Na+ channels.
- These ions enter the SMC depolarizing it, cell becomes less negative
- Depolarization of cells opens voltage-gated Ca2+ levels increase in intracellular space and bind the actin chains of myofilaments.
-Actin binding cause myofilaments to contract opposing stretch of cell membrane caused by elevated BP and thus maintain RBF and GFR.

Tubuloglomerular feedback:
- increase in GFR elevates [NaCl] in tubule fluid at the macula densa.
- NaCl uptake increases in MD cells via NKCC2 channels leading to increase ATP and adenosine
- ATP bind to P2X receptors and adenosine binds adenosine A1 receptors on SMC of afferent arteriole
- Receptor binding results in an increase in Ca2+ in SMC
- Increase in Ca2+ induces vasoconstriction of afferent arteriole, GFR decreases.

Renal clearance of any substance is the volume of plasma from which that substance is completely removed by the kidneys per unit time. Clearance of X = (Urine conc. of X) x (Urine volume per unit time)/Plasma conc. of X

Clearance of a substance that is freely filtered and fully secreted is equal to RBF - 605 ml/min. Clearance of substance that is neither reabsorbed nor secreted, just filtered equals GFR - 125ml/min. If a substance is freely filtered but fully reabsorbed, clearace will be 0. Creatine is not reabsorbed but a small amount if secreted, used to measure GFR. Plasma creatine is used as an indicator GFR, increased plasma creatine is a sign of renal diseases