Exam 5 Review:  Chapter 25:  Physiology of Glomerular Filtration

filtration - The physiological process of mechanically separating a liquid from the some or all of the undissolved particles suspended in it by passing the liquid through a semipermeable membrane with pores small enough to prevent the passage of some or all of the undissolved particles; e.g., the formation of a plasma filtrate at the glomerulus of the nephron in the kidney.

glomerular filtration - The passive process by which water and small dissolved solute molecules, including the smallest proteins, e.g., albumin (MW ~65,000 Daltons), are forced through the fenestrations of the capillary tuft within the renal corpuscle, and through the endothelial capsular membrane, and through the filtration slits formed by the pedicels of the podocytes (the visceral layer of the renal corpuscle), and into the capsular space; the main driving force is the glomerular blood hydrostatic pressure which has a gradient of ~40 mm Hg; it is measured by a variety of clinical tests known as renal clearance studies, of which the creatinine clearance test is the most popular.

glomerular filtrate - The protein-poor fluid transferred into the capsular space of the renal corpuscle as a result of the process of glomerular filtration; it consists of water and small dissolved solutes in relatively equal concentrations to their concentrations in the blood plasma; however, the larger solutes which are approaching the diameter of the filtration "pore" (molecules ranging in size from 7,000 to 70,000 Daltons) are present in correspondingly lower concentrations compared to their concentrations in the blood plasma;  ~99% of this fluid and many of the dissolved solutes must be and are selectively reabsorbed by the tubules of the kidney.


net filtration pressure - The dynamic equilibrium force which may be measured in the capsular space of the renal corpuscle which determines how much water and small dissolved solutes leave the blood in the glomerulus; this movement depends on the interaction of a set of four forces:  glomerular blood hydrostatic pressure (GBHP), capsular hydrostatic pressure (CHP), blood colloid osmotic pressure (BCOP), and interstitial fluid osmotic pressure (IFOP); NFP = GBHP - (CHP + BCOP); NFP is typically ~10 mm Hg; also see the calculation in the figure below:

The net filtration pressure is the sum of these three forces,
all measured in mm Hg:

 

            NFP    =   GBHP            - (BCOP + CHP)

                     =   Pushing force - Resisting forces

 

          Typical values might be:

          NFP    =   GBHP          -  BCOP   -  CHP

            10     =       55             -      30     -    15

 

 

glomerular blood hydrostatic pressure (GBHP) - The hydrostatic force which is the mechanical pressure exerted on the fluid of plasma by the pumping of the heart during systole and by the elastic recoil and smooth muscle contraction in the walls of the arteries between heart beats during diastole, and especially by the pressure gradient established between the afferent and efferent arterioles delivering the blood to the glomerulus, which tends to push the plasma filtrate from the capillaries of the glomerulus into the capsular space.

capsular hydrostatic pressure (CHP) - The hydrostatic force which is the mechanical pressure exerted on the plasma filtrate by the the elastic recoil of the glomerular capsule, which tends to push water and dissolved solutes from the plasma filtrate back into the capillaries of the glomerulus; this is the main force slowing the rate of filtrate production within the renal corpuscle itself.

blood colloid osmotic pressure (BCOP) - The osmotic force (water concentration gradient) which is the result of differences in water concentration between plasma and plasma filtrate, which tends to pull water from the plasma filtrate and back into the plasma in the glomerular capillaries; it results from the failure of most proteins to leave the plasma and move to the plasma filtrate, therefore, as water leaves, the proteins exert an increasing osmotic "pull" on the water in the plasma filtrate.


glomerular filtration rate (GFR) - The total amount of plasma filtrate formed by all the nephrons of the kidneys per minute; it is determined physiologically by three factors:  (1) the total surface area available for filtration, (2) the permeability of the filtration membrane, and (3) the net filtration pressure; normally, (1) and (2) do not change in healthy individuals, though they can be changed by injuries and disease processes; therefore, the body normally adjusts GFR by adjusting net filtration pressure (see above calculations) in the kidneys; therefore, GFR is proportional to net filtration pressure; it is measured by a variety of clinical tests known as renal clearance studies, of which the creatinine clearance test is the most popular; a typical GFR in healthy individuals is 120-125 mL/min.

Describe:

1. the balance of forces that determines the Net Filtration Pressure (NFP) across the endothelial-capsular membrane. Explain the effect of increased permeability on NFP. Explain the effect of renal calculi on NFP. What is the relationship between NFP and GFR?

 

Describe the balance of forces that determines the Net Filtration Pressure (NFP) across the endothelial-capsular membrane:

The net filtration pressure is the sum of these three forces, all measured in mm Hg:

Net Filtration Pressure  =  Glomerular Blood Hydrostatic Pressure - (Blood Colloidal Osmotic Pressure + Capsular Hydrostatic Pressure)

            NFP    =   GBHP            - (BCOP + CHP)

                     =   Pushing force - Resisting forces

          Typical values might be:

          NFP    =   GBHP          -  BCOP   -  CHP

            10     =       55             -      30     -    15

 

Explain the effect of increased permeability on NFP:

Increased permeability and NFP are directly proportional.  As permeability increases, NFP increases; as permeability decreases, NFP decreases.

 

Explain the effect of renal calculi on NFP:

Renal calculi (kidney stones) will tend to decrease NFP as they increase in size or number because they will obstruct the outward flow of urine from the kidney and create a back pressure in the renal tubules and collecting ducts.  That back pressure will increase Capsular Hydrostatic Pressure (CHP).

 

What is the relationship (mathematical or proportional relationship) between NFP and GFR?

NFP and GFR are directly proportional.  As NFP increases, GFR increases; as NFP decreases, GFR decreases.

2. four mechanisms of regulating Glomerular Filtration Rate (GFR).

          (1)  Renal Autoregulation:  The kidneys are able to maintain a relatively constant internal blood pressure and GFR despite changes in systemic arterial blood pressure.  There is negative feedback control from the JuxtaGlomerular Apparatus which adjusts local blood pressure and therefore blood volume within each glomerulus.  This is termed tubuloglomerular autoregulation.  The smooth muscle in the renal arterioles also makes local adjustments to blood pressure which adjust for changes in systemic arterial pressure by maintaining the appropriate pressure gradient between the afferent and efferent arterioles.  This is termed myogenic autoregulation.

          (2) Hormonal Regulation by the Renin-Angiotensin System:  The JuxtaGlomerular Apparatus monitors afferent arteriole blood pressure and water and electrolyte content in the urine in the distal convoluted tubule and will release more or less renin accordingly.  Rennin activates angiotensinogen to Angiotensin I and it is later further activated by angiotensin-converting enzyme (ACE) to Angiotensin II.  Angiotensin I and Angiotensin II, among other influences, increase systemic blood pressure and blood volume which will tend to increase GFR.

          (3) Hormonal Regulation by the antagonistic interplay of Aldosterone and Atrial Natriuretic Peptide (ANP):  Aldosterone, from the adrenal cortex, promotes retention of water and sodium ions and excretion of potassium ions, and, therefore, will tend to increase GFR.  Atrial Natriuretic Peptide (ANP) from the atrial walls of the heart promotes retention of potassium ions and excretion of water and sodium ions, and, therefore, will tend to decrease GFR. 

          (4) Neuronal Regulation by the ANS:  Sympathetic fibers innervating the kidney release norepinephrine which encourages renin release from the JuxtaGlomerular Apparatus and epinephrine release from the adrenal medulla.  This actions will lead to increased blood pressure, and, therefore, will tend to increase GFR.