Glomerular & Tubular Physiology - Topic 9

Basic Nephron Functions: Filtration - • An unselective process. • With exception of plasma proteins, substances in the

plasma exit from the blood through the filtration membrane and enter Bowman’s capsule.

Tubular Reabsorption - • A more selective process. • Substances filtered leave the lumen of the nephron

tubule and return to the blood by the peritubular capillaries.

• Large percentage occurs in the proximal tubules of the nephrons.

Tubular Secretion - • Selective movement of non-filtered substances from

blood, in the peritubular capillaries move into tubular lumen.

• Large part occurs in the distal tubules and collective ducts of the nephron.

Remaining Substances - • Substances still in the tubules are eliminated as urine. • Substances part of the blood in the peritubular capillaries leave nephrons and remain as part of the ECF.

The Filtration Membrane: • Bowman’s Capsule - Parietal layer is simple squamous and visceral layer is branching epithelium podocytes.

•1. Fenestration (pore) of glomerular endothelial cell prevents filtration of blood cells but allows all components of blood plasma to pass through. •2. Basal lamina of glomerulus prevents filtration of larger proteins. •3. Slit membrane between pedicles prevents filtration of medium sized proteins. •The basement membrane has an important role in determining filtrate, it controls passage of substances according to size and charge. •The filtration membrane is made up of the capillary endothelium, basement membrane and foot processes of podocytes of the glomerular capsule. •Cannot Pass - Blood cells, plasma proteins, large anions, protein bound minerals and hormones and most large molecules.

• Can Pass - Water, electrolytes, glucose, amino acids, fatty acids, vitamins, urea, uric acid and creatine.

Hydrostatic Pressure Along Glomerular Capillary And Arterioles: • There is relatively high hydrostatic pressure maintained along the glomerular capillary. • Sharp decreases in pressure across the afferent and efferent arterioles.

• Efferent arterioles are narrower than afferent arterioles and this helps to maintain the hydrostatic pressure in the glomerular capillaries.

• The diameter of both arterioles can be selectively adjusted to alter the GFR. • The maintenance of steady hydrostatic pressure along the glomerular capillary is because of the high pressure exerted by

the efferent arteriole.

Glomerular Filtration And Reabsorption: • The pair of kidneys receives about 20% of the cardiac output. • After passing through afferent arteriole, about 20% of plasma flowing through glomeruli is filtered into Bowman’s capsule. • 80% of plasma is not filtered and passes into the efferent arteriole unchanged. • Urine flow rate is 1-2 mL/min and is determined largely by the rate of reabsorption of the filtered load. • Urine is a combination of filtration, secretion and reabsorption of molecules and substances. • 99% of filtered water, sodium etc is returned into the plasma.

Glomerular Filtration Rate: • Glomerular filtration rate (GFR) is the volume of fluid filtered from the renal glomerular capillaries into the Bowman’s

capsule per unit time. • Normal filtration rate is 125 mL/min and depends on net filtration pressure (NFP). • NFP can be adjusted by changing the glomerular capillary hydrostatic pressure and can be achieved by altering the tone of

afferent and efferent arterioles.

Net Filtration Pressure: • The pressure driving the fluid out of the capillary at any given point, we calculate the net filtration pressure. • The outward pressures (HPc and OPif) — the inward pressures (HPif and OPc). • As a result, fluid moves from the capillary into the interstitial space. • NFP at the venous end is a negative number. This means that reabsorption, not filtration is occurring and so fluid moves

from the interstital space into the capillary. • Hydrostatic pressure in the capillary pushes fluid out of the capillary. • Osmotic pressure in the capillary pulls fluid into the capillary. • Hydrostatic pressure in the interstital fluid pushes fluid into the capillary. • Osmotic pressure in the interstitial fluid pulls fluid out of the capillary. • NFP comprises all the forces acting on a capillary bed - NFP = (HPc - HPif) - (OPc - OPif).

Driving Forces Of Water And Solutes - • Glomerular Hydrostatic Pressure (HPgc): Glomerular blood pressure and equivalent to HPc in starlings law equation. • Bowman’s Capsule Osmotic Pressure (OPbc): Equivalent to OPif in the starlings equation.

Forces Opposing Movement Of Water And Solutes - • Colloid Osmotic (Oncotic) Pressure (OPgc): In glomerular capillaries and equivalent to OPc in the starlings equation. • Capsular Hydrostatic Pressure (HPcs): Exerted by fluid in Bowman’s capsule and equivalent to Hpif in starlings equation.

Regulation Of The GFR: • GFR remains constant even with variations in blood pressure, renal plasma flow rate and cardiac output. • Renal Auto-Regulation (Intrinsic System) - Maintains a nearly constant GFR through myogenic control and tubuloglomerular

feedback. • Neural Controls - Extrinsic system. • Hormonal Mechanism - Renin-angiotensin (aldosterone) system.

Myogenic Control: • Afferent arterioles respond to changes in pressure in renal blood vessels. • Systemic increases in blood pressure stretch afferent arterioles. • Smooth muscle contraction reduces diameter of arterioles and returns GFR to previous level in seconds.

Tubuloglomerular Feedback: • Made of juxtaglomerular cells and the macula densa. • Juxtaglomerular cells in afferent arterioles (sometimes efferent) which contact the macula densa of the distal convoluted

tubule. • The macula densa cells are specialised columnar epithelial cells lining the end of the ascending loop of henle and

beginning of the DCT at point of contact.

Feedback Loop: • Macula densa senses NaCl concentration and flow rate in the tubule. Secretes locally active (paracrine) chemicals which act

on the adjacent afferent arteriole to alter diameter. • This alters glomerular hydrostatic pressure —> alters NFP —> alter glomerular filtration rate as part of feedback loop.

Juxtaglomerular (Granular) Cells: • Modified smooth muscle cells of afferent arteriole and involved in hormonal control of the GFR. • Secretes renin in response to B1 adrenergic stimulation, decrease in renal perfusion pressure and decrease in NaCl in

filtrate in the DCT.

Macular Densa & Tubuloglomerular Feedback: • High GFR - Insufficient time for NaCl

reabsorption which stimulates macula densa cells to induce vasoconstriction of afferent arteriole —> less flow to glomerulus.

• Low GFR - Vasoconstriction is relieved and afferent arteriole dilates causing more blood flow.

• If efferent arterioles were to constrict, GFR would go up, increasing pressure within the glomerulus, NFP and GFR.