Glomerular Filtration

Proximal Tubule Function (PCT)

Reabsorption and secretion (only here secretion occurs). Isoosmotic reabsorption of organic nutrients, ions, and water. Secretion of metabolites and xenobiotic molecules. 

Renal Corpuscle Function

Filtration of protein-free plasma from the capillaries into the capsule

Loop fo Henle Function

Reabsorption of ions in excess of water to create dilute fluid.

Distal Nephron

Regulated reabsorption of ions and water for salt and water balance and pH homeostasis

Ultrafiltrate

Contains H2O and small molecules

Doesn’t contain large proteins, RBC

Albumin is filtered & reabsorbed by the PCT

Glomerular Filtration

Nonspecific process, where plasma passing through the glomerulus is filtered, with the remainder going to the peritubular capillaries.

Portion of RBF entering glomerulus capillaries is filtered into Bowman’s space.

Mesangial Cells

Creating a support structure for the tuft of capillaries

Influence filtration by altering the SA of the filtration slits

Secreted cytokines associated with immune and inflammatory processes

Glomerular Filtration Barrier

1. Capillary endothelium

2. Basement membrane

3. Podocyte

Capillary Endothelium

Lined with a lattice-like layer of glycoproteins (glycocalyx) with (-) charged proteins help repel (-) charged plasma proteins

Fenestrated pores too small for blood cells and plasma proteins, but big enough for dissolved solutes and some plasma proteins.

Gycocalyx

(-) charged proteins help repel (-) charged plasma proteins

Basement Membrane

Acellular layer of ECM

Consists of (-) charged glycoproteins, collagen, and other proteins

Acts like a coarse sieve, excluding most plasma proteins from the fluid that filters through

Podocyte

Specialized epithelium

Attached to the basement membrane by foot processes (long cytoplasmic extensions that wrap around capillaries)

Between foot processes are filtration slits, which are bridged by thin diaphragms (contains several structural unique proteins, including nephrin and podocin)

Capillary Pressure 

Starling Equilibrium

Hydrostatic pressure (bp)

Colloid Osmotic Pressure (protein-based, more proteins in blood vs Bowman’s space)

Fluid Pressure (due to fluid in Bowmans Capsule

Glomerular Filtration Rate (GFR)

Fluid movement due to filtration across the wall of a capillary is dependent on the balance between the hydrostatic pressure gradient and the colloid osmotic pressure gradient across the capillary 

The amount of fluid from the arterial endothelium of capillaries equals almost exactly the fluid returned to the circulation by absorption. The lymphatics eventually returns the flight discrepancy.

GFR

125 mL/min (180 L/day)

GFR Calculation

Renal plasma flow (RPF) / bp

Filtration Fraction

GFR / RPF

SA of glomerular capillaries

Permeability to filtration slits

Usually about 20%, indicating 80% of blood continues its pathway through renal circulation

Active Reabsorption

Na+ is primary driving force for most of the time causing secondary transport

Plasma proteins

Passive Transport

Nitrogenous waste products urea (dependent on osmosis of water, which is initiated by Na+ transport)

Reabsorption Based On

Saturation, specificity, competition

Secretion

Depends primarily on membrane transport (active)

K+ and H+

Organic compounds (metabolites produced and substances brought into the body)

Transporters have broad specificity 

Organic anion transporter family

Renal Handling

Substance reabsorbed, secreted, or both

Clearance

The rate at which that solute disappears from the body by excretion or by metabolism

C_albumin

Usually around 0 with none being filtered (if filtered it is then absorbed)

C_glucose

Usually around 0 but it is filtered & completely reabsorbed 

Inulin

The most accurate substance to measure GFR

Small inert polysaccharide (filtered by glomeruli)

Neither secreted nor reabsorbed

Amount filtered = amount excreted

Creatinine

Muscle waste product (AA)

Endogenous (produced by the muscle)

Production and breakdown rates are relatively constant

A small amount is reabsorbed and usually excreted

Kidney Function

Regulates homeostasis

Filtrate is modified by reabsorption/secretion

Able to sense volume keeping ECF volume stable

Sodium Homeostaiss

The main determinant of the osmolarity of ECF

Sensors of regulation monitors changed in the ECF volume not concentration composition

ECF Equilirbium

Osmolar with ICF

Increase in Na+

ECF volume expands → activates mechanism to lose Na+ to restore ECF back to normal

Decrease in Na+

ECF volume contracts → activated mechanisms to conserve Na+ to restore ECF volume back to normal

PCT Sodium Transport

Entry: Na+ - H+ antiporter

Export: Na+ - K+ ATPase pump

Loop diuretics inhibit Na+ intake

K+ PCT

Filtered K+ is reabsorbed 90% of time

Through paracellular pathaway 

K+ in Thick Ascending Limb of Henle

Both paracellular and transcellular reabsorption of K+

Aldosterone

Distal delivery of Na+

Urine flow rte

Calcium in Kidney

Deals with the ionized form (filtered)

Based on how much it is resold and ingested

Paracellular and passive in parallel to Na+ and water (80%)

Active and regulated by PTH in the distal tubule (15%)

Regulation of Calcium 

Parathyroid, bone, gut, and kidney

PTH

Calcidiol → Calcitriol (vitamin D)

FGF-23

Parathyroid Hormone (PTH)

Polypeptide secreted form the PT glands in response to a decrease in plasma [Ca2+] 

Change is sensed by the Ca2+ sensing receptor in the cell membrane of PT cells

Increased [Ca2+] activated receptor, PTH is decreased, resulting in less release of Ca2+ and phosphorus from bone and across the gut, and less Ca2+ retention and phosphorous excretion

Phosphorous

Most is filtered and reabsorbed in the PCT, with most being deposited in bone crucial for cellular processes

PCT Absorption of Phosphorous

Energy-dependent process via sodium phosphate transporters

The amount of phosphate reabsorbed is determined by the abundance of the cotransporters in the apical membrane of PCT.

FGF-23

Hormone-suppressing phosphate reabsorption and vitamin D hormone synthesis in the kidney

Secreted by osteocytes in response to increased calcitrol 

Magnesium

Reabsorption occurs in the Loop of Henle with some at DCT

Passive paracellular transport mediated by tight junction proteins

Depends on transepithelial voltage gradient created by Na+ K+ 2Cl- cotransporter (NKCC2)

Loop diuretics inhibit NKCC2 and cause hypomagnesmia