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Glomerular Filtration: Physiology with Elements of Pathophysiology

Renal Physiology
Where does filtration occur?
In the renal corpuscle as fluid moves under pressure across the wall of glomerular capillaries into Bowman's space.
Describe the pathway of fluid through the renal corpuscle.
Perfusion of glomerular capillaries -> filtration of plasma -> formation of urine.
Sympathetic nerves in the renal corpuscle project where?
To the granular and smooth muscle cells.
What are mesangial cells?
Immunoreactive transformed smooth muscle cells that can contract in response to circulating vasoactive substances impeding glomerular blood flow and filtration.
What forms the juxtaglomerular apparatus?
Granular cells, macula densa, and external mesangial cells.
Describe the juxtaglomerular apparatus
At a site of its transition into the distal tubule, the thick ascending limb of the Loop of Henle makes a contact with the afferent arteriole in each nephron.
What are the functions of the cells of JGA?
Granular cells (renin), macula densa (monitor flow rate of filtrate.
What is the glomerular filtration barrier?
The wall of glomerular capillaries.
What does the glomerular filtration barrier do?
Controls passage of substances from plasma into the renal tubule.
What are the layers of the glomerular filtration barrier?
Leaky endothelium (pores/fenestrae), basement membrane (porous matrix of negatively charged glycoproteins), podocytes (specialized epithelial cells with interdigitating pedicels separated by filtration slits).
How are substances in the blood filtered?
Through capillary fenestrae between endothelial cells, the filtrate then passes across the basement membrane and through slit pores between the foot processes and enters the capsular space, from here, the filtrate is transported to the lumen of the PCT.
Filterability of substances depends on what?
Molecular weight (radius in angstroms) and molecular charge.; large molecular radius and egative charge impedes filtration.
What substances filter easily?
Water, urea, glucose and inulin.
What substances don't filter?
Albumin and hemoglobin.
What substances filter moderately?
Compare the permeability of glomerular capillaries with systemic capillaries.
Glomerular capillary walls are more permeable.
What is filtrate?
Water and dissolved solutes like ions, glucose, amino acids, etc.; pass through the glomerular capillary wall and move into the Bowman's space and proximal tubule.
What is the filtration coefficient?
Kf, a measure of permeability; 100x greater for the golmerular capillaries than systemic capillaries.
What doesn't pass through the walls of golmerular capillaries?
Blood cells and most plasma proteins.
How are proteins reabsorbed in the proximal tubule?
What are Tamm-Horsfall proteins?
Proteins synthesized within the renal tubule and normally detected in urine; unclear function, may prevent calcification and formation of kidney stones.
How much protein should be found in urine?
Only trace amounts.
When can the filtration barrier leak?
When glomerulus isn't healthy.
What is proteinuria.
Loss of proteins in urine due to the damaged leaky golmerular capillaries.
What can profound proteinuria lead to?
Low plasma protein concentration and a decrease of plasma oncotic pressure; 3g/day.
What happens when there is a decrease in plasma oncotic pressure?
Fluid shifts into interstitial space; swelling.
What does oncotic pressure do?
Helps keep water inside the vessel, depends on protein concentration.
What is a typical feature of the nephrotic syndrome?
Swelling/edema due to profound decrease in plasma protein concentration (hypoalbuminemia).
Diseases of the glomerulus cause what?
Breakdown of glomerular capillaries, protein leak and reduction in: glomerular perfusion, glomerular filtration (GFR), urine formation and renal clearance of plasma.
What is the clinical presentation of glomerular diseases?
Nephritic and Nephrotic Syndromes.
What is glomerulonephritis?
Inflammation of the glomerulus; may lead to rupture of glomerular capillaries, reduced renal blood flow and filtration = renal insufficiency (very low filtration = renal failure); decreased urine formation (oliguria < 500 ml/day; anuria < 100 ml/day; or cessation of urine formation); often associated with hematuria and proteinuria.
What is nephritic syndrome?
Hematuria, oliguria, hypertension and low/moderate proteinuria.
What is nephrotic syndrome?
Permanent sclerotic damage or scarring, exception - curable minimal change disease; profound proteinuria, hypoalbuminemia, edema, hyperlipidemia.
What is the treatment for many glomerular diseases?
Describe minimal change disease.
Affects children and manifests as classical nephrotic syndrome, not detectable by light microscope.
Describe acute kidney injury?
Acute renal failure; rapid severe drop in the rate of filtration.
Describe chronic renal disease.
Discovered and diagnosed in primary care by GFR decrease measured by accumulation of creatinine.
Many glomerular capillary diseases reduce what?
The negative charge on the capillary wall which results in abnormally high passage of proteins through the filtration barrier - proteinuria.
What are factors that cause glomerular diseases?
Antigens may pass through endothelium enter the basement membrane and mesangial matrix, triggering inflammation; inflammation causes proteinuria and proliferation of mesangial cells.
What are mesangial cells involved in?
Regulation of blood flow and filtration (Kf) in the glomerulus (circulating vasoactive compounds may pass through endothelium and reach mesangial cells, causing their contraction/relaxation); immunological responses (macrophage-like function).
How often does chronic renal failure develop?
Within ten years in every third patient with diabetes mellitus.
Describe diabetic nephropathy.
Usually begins with an increase in glomerular filtration and proteinuria; with time, filtration declines as mesangial cells proliferate and compress the glomerular capillaries, impeding perfusion; filtration declines as the situation progresses to end-stage renal disease when the kidneys are no longer able to detoxify plasma and maintain its proper composition. Patients require dialysis or renal transplant.
What is the glomerular filtration rate (GFR)?
Volume of filtrate per unit time (ml/min); normal GFR in adults = 100 ml/min; GFR decreases, disease progresses; GFR increases, recovery of kidney funciton.
What force favors filtration?
Hydrostatic pressure in glomerular capillary, PH.
What are the opposing forces for filtration?
Hydrostatic pressure in Bowman's space (PBS), oncotic pressure in glomerular capillary (PO)
What is the net filtration pressure?
What is the equation for GFR?
GFR = Kf x NFP.
What happens to NFP as it goes along the length of the glomerular capillary?
It decreases.
What happens to plasma protein concentration and PO along the length of the capillaries?
They increase, causing NFP to decrease.
GFR and PH depend on what?
Diameter of afferent and efferent arterioles.
What happens when the afferent arteriole is constricted?
Increase in arteriolar resistance, decrease in renal blood flow, PH, and GFR.
Name some vasoconstrictors.
Sympathetic nerves (NE), angiotensin II, vasopressin, endothelin.
What happens when the efferent arteriole is constricted?
RBF decreases, GFR increases.
What are the clinical implications of increased GFR?
Glomerular hypertension in diabetic nephropathy, glomerular capillaries leak, increased PH.
What helps protect against glomerular hypertension in diabetic nephropathy?
Anti-angiotensin medications; dilation of the efferent arteriole reduces hypertension inside the glomerulus, GFR and loss of proteins.
What happens to RPF and GFR with decreased plasma protein concentration?
No change to RPF but an increased GFR.
What happens to RPF and GFR with increased plasma protein concentration?
No change to RPF but a decreased GFR.
What happens to RPF and GFR with constriction of ureter?
No change to RPF but a decreased GFR.
What impedes glomerular filtration?
A rise in PBS.