What is a nephron?
It is a basic structural and functional unit of the kidney.
Name the components of the nephron.
As per diagram:
1. Glomerulus, 2. Efferent arteriole, 3. Bowman's capsule, 4. Proximal convoluted tubule, 5. Cortical collecting duct, 6. Distal convoluted tubule, 7. Loop of Henle, 8. Papillary duct, 9. Peritubular capillaries, 10. Arcuate vein, 11. Arcuate artery, 12. Afferent arteriole, 13. Juxtaglomerular apparatus
What is the purpose of the nephrons?
To regulate the concentration of water and soluble substances by filtering the blood, reabsorbing what is needed and excreting the rest as urine. A nephron eliminates wastes from the body, regulates blood volume and blood pressure, controls levels of electrolytes and metabolites, and regulates blood pH.
What is glomerulus?
It is a dense network of capillaries within the Bowman's capsule where filtration occurs.
What is Bowman's capsule.
It houses the glomerulus and is a space where the filtered water and solutes from the glomerulus enter.
What are the 3 layers of the glomerular capillary membrane that make up the filtration barrier and their characteristic?
From inner to outer:
endothelium: have holes called fenestrae for filtration
basement membrane: meshwork of collagen and proteoglycan fibrillae
epithelium (podocytes): These cells are not continuous but have long footlike processes (podocytes) that encircle the outer surface of the capillaries. The foot processes are separated by gaps called slit pores through which the glomerular filtrate moves.
What substances are not filtrated by the glomerular capillaries and what allows the glomerulus to be selective in its filtration?
Macromolecules such as proteins and RBCs (>50-100 angstrom), microsolutes such as calcium that are bound to proteins, and negatively charged particles (both macro and micro solutes) are not easily filtered due to their large size and/or electrostatic repulsion created by the negatively charged characteristic of the basement membrane of the glomerulus.
(Size and electrical charge determine filterability)
How does the blood enter into and exit out of the glomerulus?
Enters into the afferent arteriole and exits through efferent arteriole.
(Both are arteries and not vein)
What is responsible for creating the negative charge in the basement membrane of the glomerulus capillary membrane?
What is GFR and its normal value?
It is the volume of plasma that is filtered from the glomerulus per minute.
What percentage of the CO is the renal blood flow and what is its volume?
20% of CO (1200mL/min)
The kidney receives the second highest percentage of CO, after the liver.
How much percentage of the glomerular filtration is converted to urine?
What four factors determine GFR?
1.The ultrafiltration coefficient
•This depends on capillary permeability and surface area available for filtration
•Since there should be no free protein in Bowman’s Space the net direction of this force should oppose filtration
3.Net hydraulic pressure
•Drives fluid from capillaries into Bowman’s Space
4.Capillary plasma flow rate
•Higher flow = greater filtration
What is the net filtration pressure in the glomerulus?
How does the factors below affect GFR?
glomerular capillary filtration coefficent
Bowman's capsule hydrostatic pressure
glomerular capillary colloiod osmotic pressure
glomerular capillary hydrostatic pressure
glomerular capillary filtration coefficent: increases filtration
Bowman's capsule hydrostatic pressure: decreases filtration
glomerular capillary colloid osmotic pressure: decreases filtration
glomerular capillary hydrostatic pressure: increases filtration
What three variables affect glomerular hydrostatic pressure?
(1) arterial pressure
(2) afferent arteriolar resistance
(3) efferent arteriolar resistance
How does constriction or dilation of afferent and efferent arterioles affect GFR?
afferent arteriole: decreases GFR
efferent arteriole: increases GFR (severe constriction will decrease GFR)
afferent arteriole: increases GFR
efferent arteriole: decreases GFR
What affects renal oxygen consumption?
sodium reabsorption (Na+/K+ ATP)
What capillary system is responsible for the reabsorption of fluid?
peritubular capillaries that surrounds the proximal and distal tubules
vasa recta that surrounds the loop of henle in the juxtamedullary nephrons
What is auto regulation?
The kidney's ability to maintain a relatively constant GFR and to allow precise control of renal excretion of water and
solutes over a range of MAP 80-200 mmHg
This is accomplished by the constriction or dilation of afferent and efferent arteriole and sodium sensitivity of the macula densa
Where is macula densa?
The macula densa is a specialized group of
epithelial cells in the distal tubule that comes in close
contact with the afferent and efferent arterioles.
It is sensitive to the level of the sodium excretion and modulates the constriction/dilation of the afferent/efferent arterioles and regualtes the release of renin.
What is juxtaglomerular complex consist of?
The juxtaglomerular complex consists of macula densa
cells in the initial portion of the distal tubule and juxtaglomerular
cells in the walls of the afferent and efferent arterioles.
It provides feedback control of GFR and blood flow in the same nephron
What is the function of macula densa?
If it senses a low volume of Na+ in the distal tubule (decreased GFR), it sends a feedback to decrease afferent arteriolar resistance (dilate) and causes the release of renin.
If it senses a high volume of Na+ in the distal tubule, it sends a feedback to increase afferent arteriolar resistance.
What do principal cells do?
Reabsorb sodium and water from the lumen and secrete potassium into the lumen
Tubular reabsorption is nonselective.
It is highly selective.
What are the passive and active mechanisms of tubular reabsorption and secretion?
Simple diffusion of lipid soluble agents or gasses (or osmosis of liquid)
Facilitated- uses a protein channel or carrier (passive)
Active transport : uses energy
secondary active transport : moves solute against a concentration gradient coupled to the movement of another solute
What is transport maximum?
For most substances that are actively reabsorbed or secreted, there is a limit to the rate at which the solute can be transported due to saturation of the specific transport systems involved when the amount of solute delivered to the tubule (referred to as tubular load) exceeds the capacity of the carrier proteins and enzymes involved in the transport process.
Ex: in DKA the filtered glucose load exceeds the capability of the tubules to reabsorb glucose, urinary excretion of glucose occurs
Where does the primary reabsorption occur?
All absorption is iso-osmotic
What is unique about the proximal tubule?
•Has extensive microvilli
•All reabsorption is iso-osmotic
•Only region of the nephron where carbonic anhydrase is present on the luminal membrane
•All filtered amino acids and glucose are reabsorbed here via co-transport with Na
•Organic acids and bases are secreted (such as creatinine, ATB, toxins, etc.)
•Site of ammonia secretion
•65% of filtered water and solutes are reabsorbed
•Use Na+/K+ ATPase primarily
What is the best approach to measuring creatinine clearance?
24 hour urine collection
What takes place in the descending tubule?
•Highly permeable to water (20%) and moderately permeable to solutes
•The function of this segment is to allow simple diffusion of substances through its walls
What takes place in the ascending thin segment?
•Virtually impermeable to diffusion of water
•Some reabsorptive capacity for ions such as calcium, bicarbonate, and magnesium
What takes place in the ascending thick segment?
•The most important segment of the loop of Henle is the thick ascending limb (TAL)- this is the “diluting segment of the nephron”and important in cocentrating urine.
•The key feature of the TAL is that it is impermeable to water while solute is pumped out of the tubular fluid.
•The luminal membrane has a 1Na 1K 2Cl transporter pump. (this is the target site of lasix and the only nephron segment where Cl is actively transported)
•Metabolically active (uses Na+/K+ ATPase channels)
Describe the early distal tubule.
•The first portion of the distal tubules forms part of the juxtaglomerular complex (macula densa) to provide feedback control of GFR and blood flow in the same nephron
•Similar reabsorptive characteristics as the thick segment of the ascending limb of the loop of Henle
•Virtually impermeable to water
•Tubular fluid becomes more dilute as solutes are reabsorbed
•Thiazide works on this segment
What takes place in the late distal tubule?
•Control the degree of dilution or concentration of urine
•Water permeability is controlled by the presence or absence of ADH (vasopressin)
•High levels of ADH make the tubular segment permeable to water and absence of ADH makes tubular cells virtually impermeable to water (alcohol)
•Reabsorption of sodium and secretion of potassium -- the rate which is controlled by aldosterone
•Secretion of hydrogen by hydrogen-ATPase against a large concentration gradient (1000 to 1)
•Principal cells and intercalated cells are located here
Where are the principal cells and intercalated cells located?
late distal and cortical collecting tubules.
What is the function of the intercalated cells?
Reabsorb bicarbonate and potassium ions and secrete hydrogen into the lumen (important for acid-base regulation by the kidneys)
What is medullary collecting duct?
–Final site for processing the urine
–Reabsorbs less than 10 percent of the filtered water and sodium
–Permeability to water is controlled by the level of ADH
–Urea -- collecting duct is permeable to urea and reabsorption of urea into the interstitial around the collecting duct contributes to the ability to form concentrated urine.
–Collecting duct is capable of secreting hydrogen ions against a large concentration gradient which is important for regulating acid -- base balance
What are the four actions of the nephron?
At what site of the nephron does the loop duretics work?
Thick ascending lumen (TAL) in the loop of henle
Where in the nephron is creatinine secreted?
Proximal convolute tubule
What is the function of carbonic anhydrase?
It is an enzyme that facilitates the reaction of CO2 and H2O to produce H+ and HCO3- and vice versa. In the renal system, it helps to regulate acid-base balance by producing HCO3-