PSL 250: Topic 13 - Renal Physiology
glomerular Filtration Membrane
1) capillary endothelium 2) 2 fused basement membranes 3) pedicels of podocytes 4) filtration slit diaphragm
What is hemodialysis and which of these processes does this clinical treatment replicate?
Hemodialysis: artificial kidney to filter wastes out of the blood.
Where is it located? NKCC2
Located in the apical membrane of the epithelial cells (near the luman of tube) of the thick ascending limb of the loop of Henle.
antidiuresis
a condition resulting from excessive reabsorption of water in the kidneys Presence of ADH (small volume of concentrated urine)
Can you mechanistically describe the functions of ADH, aldosterone, PTH, calcitriol and thiazides on the DCT? aldosterone
aldosterone increases the number of sodium-potassium pumps. more sodium into blood, water follows. Increases water reabsorption into blood
How much water is reabsorbed by the DCT?
depends on ADH? 10-15 percent?
glomerular filtration
hydrostatic pressure drives water and solutes across the glomerular filtration membrane and into Bowman's space; glomerular filtrate
increase potassium in plasma
hyperkalemia
increase in Na+ in plasma
hypernatremia
decrease potassium in plasma
hypokalemia
decrease Na+ in plasma
hyponatremia
in the tubular fluid, the fluid gets more concentrated with solute as you move down the collecting duct because
if ADH is present, water is lost Gradient that is already present allows ADH to work
A ______consists of a Bowman's capsule and a glomerulus.
renal corpuscle
in the tubular fluid, the fluid gets less concentrated as you move up the ascending limb because
solute in moving into medullary tissue
secondary active transport
used to drag amino acids and Na+ back into PCT cell (by SGLT) so it can eventually get to blood. Low sodium and glucose concretion created by primary active transport. Amino acids have specific transporters as well. Caffine and theophylline cause dieresis at the PCT by enhancing Na+ and H2O excretion. Na+ stays in filtrate (in tubule of nephron) and it is excreted.
in the tubular fluid, the fluid gets more concentrated with solute as you move down descending limb because
water moves into medullary tissue
Loop of Henle - 3 regions: descending limb, Henle's loop, ascending limb - the loop of Henle and the vasa recta work together to concentrate the medullary tissue with solute (salt and urea); countercurrent multiplication
- 3 regions: descending limb, Henle's loop, ascending limb - the loop of Henle and the vasa recta work together to concentrate the medullary tissue with solute (salt and urea); countercurrent multiplication Water reabsorption occurs at the DL and salt reabsorption occurs at the AL
Loop of Henle:
- 3 regions: descending limb, Henle's loop, ascending limb. - The loop of Henle and the vasa recta work together to concentrate the medullary tissue with solute (salt and urea). Reabsorption (lumen to blood) is occuring in both the ascending and descending loops. Ascending is mostly solutes (salt or solute) and descending is usually water. only does reabsorption
Proximal Convoluted Tubule (PCT)
- 60-70% reabsorption of sodium and water - 100% reabsorption of glucose and amino acids - secretion of ions (e.g., ammonium, H+, HCO3-), drugs and toxins caffeine and theophylline cause diuresis by enhancing Na+ and H2O excretion
Proximal convoluted tubule (PCT):
- 60-70% reabsorption of sodium and water. - 100% reabsorption of glucose and amino acids. - Secretion of ions (e.g., ammonium, H+, HCO3-), drugs and toxins caffeine and theophylline cause diuresis by enhancing Na+ and H2O excretion mostly reabsorption, but does secretion and reabsorption
Distal Convoluted Tubule (DCT)
- Reabsorbs sodium ions (regulated by aldosterone). - Reabsorbs calcium ions (regulated by PTH and calcitriol). - Secretion of drugs and toxins. mostly secretion, but does secretion and reabsorption
Collecting Duct
- Reabsorbs sodium ions (regulated by aldosterone). - Reabsorbs water (regulated by ADH/AVP and aldosterone). - Reabsorbs urea and bicarbonate. - Secretes proton does reabsorption and secretion
Distal Convoluted Tubule (DCT)
- reabsorbs sodium ions (regulated by aldosterone) - reabsorbs calcium ions (regulated by PTH and calcitriol) - secretion of drugs and toxins
Collecting Duct
- reabsorbs sodium ions (regulated by aldosterone) - reabsorbs water (regulated by ADH/AVP and aldosterone*) - reabsorbs urea and bicarbonate - secretes proton
Can you use your knowledge of the anatomy of a nephron and the renal vasculature to describe where these renal processes occur?
-Proximal convoluted tubule (PCT): -Loop of Henle -Distal Convoluted Tubule (DCT) -Collecting Duct
The reabsorption of Na+ in the DCT is regulated by_______while the reabsorption of Ca++ is regulated by________
-aldosterone -PTH
ust like the adrenal glands and brain, the functional parts of the kidney have an outer portion called the_____and an inner portion called the________
-cortex -medulla
How does a glomerulus differ from a renal corpuscle?
Bowman's capsule + the glomerulus = renal corpuscle.
tubular Reabsorption and Secretion
-movement of water and solutes between tubular fluid and peritubular fluid (i.e., nephron ↔ ECF ↔ peritubular capillaries) - 125 ml/min filtered; 123-124 ml/min reabsorbed; 1-2 ml/min urine; 1.44-2.88 L/day; polyuria (e.g., diabetes) → ↓ BP → shock → death - water, ions (e.g., Na+) and organic nutrients (e.g., glucose) are tightly regulated and virtually 100% reabsorbed - wastes are incompletely reabsorbed; this is the whole point, right
_________are the cells that cover the capillaries of the glomerulus. They have many feet (called pedicels) that interdigitate with the pedicels of their neighbors. They compose the _______layer of Bowman's capsule.
-podocytes -visceral
Can you draw and label all of the segments of a nephron?
1. Beginning of nephron (Bowman's capsule with glomerulus which are capillaries responsible for filtration)- cortex 2. proximal convoluted tubule- cortex 3. descending loop of henley- medulla 4. ascending loop of henley (thick ascending limb at its highest point)- medulla 5. distal convoluted tubule- cortex 6. collecting ducts or connecting tubule goes into minor calyx from there
Place the following renal circulation in the correct order following the flow of blood.
1. interlobar artery 2. arcuate artery 3. interlobular artery 4. afferent arteriole 5. glomerulus 6. efferent arteriole 7. peritubular capillaries 8. interlobular vein 9. arcuate vein 10. interlobar vein
protein-free ultrafiltrate
1.5 L urine/day gets dumped into PCT
numbers associated with EFP equation
16 mmHg = (60 mmHg + 0 mmHg) - (29 mmHg = 25 mmHg)
How much water is reabsorbed by the PCT?
60-70% reabsorption of sodium and water.
How does secretion differ from excretion?
A secretion is a substance that is moved into a body space or onto the surface of the body (e.g., mucus in the lungs, fluid in the kidney and sweat). An excretion is a waste removed entirely from the body (e.g., urine and feces).
Can you mechanistically describe the functions of ADH, aldosterone, PTH, calcitriol and thiazides on the DCT? ADH
ADH increases permeability to water.
What vessel feeds the glomerulus?
Afferent arteriole.
How much water is reabsorbed by the ascending limb of the loop of Henle?
Ascending limb of the loop of Henle is impermeable to water. Permeable to salt (not water) it is important for the reabsorption of water because it creates the concretion gradient (higher Na+ and urea in medullary tissue) so water follows the solute
Why is glucose normally not detected in the urine? Under what circumstances would it be?
Because there is 100% reabsorption of glucose, along with amino acids. Diabetic or kidney failure.
How do caffeine and theophylline cause diuresis in the PCT?
Caffeine and theophylline stimulate the secretion of renin by inhibition of adenosine receptors and removal of the general inhibitory brake function of endogenous adenosine.
Can you mechanistically describe the functions of ADH, aldosterone, PTH, calcitriol and thiazides on the DCT? Calcitriol
Calcitriol inhibits PTH synthesis therefore inhibits calcium absorption.
Can you describe how the tubular concentrations of water, ions, nutrients and wastes are altered as they pass through the PCT?
Cells in the hypothalamus detect low water content in blood. ADH is released into blood by the hypothalamus, acting on the distal tubule and collecting duct. This causes more water to be reabsorbed into the peritubular capillary. Therefore, blood volume increases. As the blood becomes more dilute, this is detected by the hypothalamus, causing ADH secretion to stop. So, in other words, the concentration shift is what causes the filtering to happen with ADH helping. collection duct is usually impermeable to water unless ADH is present
The cross-sectional anatomy of a kidney?
Cortex: Bowman's capsule, PCTs (proximal convoluted tubule) and DCTs. Medulla: composed of 6-7 renal pyramids containing loops of Henle and collecting ducts. Collecting ducts open into minor calyces which open into major calyces which open into the renal pelvis.
What are the two different types of nephrons?
Cortical nephrons (80%)- filter blood and forming urine juxtamedullary nephrons (20%).- filter blood too but also create a solute gradiant in medullary tissue (makes medullary tissue highly concentrated in salt and urea). has vesa recta
Can you compare and contrast the structure and function of the two types of nephrons?
Cortical nephrons have their loops of Henle in the renal medulla near its junction with the renal cortex, while the loops of Henle of juxtamedullary nephrons are located deep in the renal medulla. Both are surrounded by peritubular capillaries and the juxtamedullary nephrons have special peritubular capillaries around their loops of Henle referred to as the vasa recta. Bowman's capsule, PCTs and DCTs are ways in the cortex no matter what. Collecting ducts and loops of henley are usually in medulla.
How much water is reabsorbed by the The descending limb?
Descending limb of the loop of Henle reabsorbs majority of water. Not permeable to solute (salt)
The goal of the nephron is to remove waste products from the blood, NOT water. But some water must be lost as a vector to transport these wastes. 99% of water is absorbed in a normal, healthy person. If a person is chronically not reabsorbing the appropriate amount of water, they may have a condition known as_______
Diabetes
Clinically, why would we want to inhibit the NKCC2? Physiologically, what happens when the NKCC2 is inhibited?
Dilute the urine more to reduce BV and thus reduce BP. Impairment of sodium reabsorption in the thick ascending limb of the loop of Henle.
What renal processes occur in the DCT?
Distal Convoluted Tubule (DCT) reabsorbs sodium ions (regulated by aldosterone), reabsorbs calcium ions, and secrets drugs and toxins.
What can conditions can cause this phenomenon? Polyuria
Drinking excessive amounts of fluids (polydipsia), particularly water and fluids that contain caffeine or alcohol. It is also one of the major signs of diabetes mellitus. When the kidneys filter blood to make urine, they reabsorb all of the sugar, returning it to the bloodstream.
What vessel drains the glomerulus?
Efferent arteriole.
Cortical nephrons have glomeruli in the cortex while juxtamedullary nephrons have glomeruli in the medulla. T/F
False
what type of capillaries make up the glomerulus?
Fenestrated capillaries.
What are the functions of peritubular capillaries?
First, these vessels deliver oxygen and nutrients to the epithelial cells. Second, they are responsible reabsorption of tubular fluid and secretion of solutes into the tubular fluid. Wrap around the nephron. In both cortical and juxtamendullary nephrons
What is glomerular filtration? What is its purpose?
Glomerular filtration is the process by which the kidneys filter the blood, removing excess wastes and fluids from blood plasma. Its purpose is to filter the blood so that waste products (e.g., urea, uric acid and creatinine) are removed from the circulation. Plasma is what goes into glomerulus and it is pushed out through membrane (filtration)- selective based on size, big things left in blood and leaves via efferent arteriole. Small things go through sit in Bowmans space and eventually go to the renal tubule (for excretion)
How to calculate whether blood moves in/out
If you subtract the forces favoring reabsorption from the forces favoring filtration, you end up with the effective filtration pressure, 16 mmHg. EFP or effective filtration pressure= (glomerular hydrostatic pressure +capsular osmotic pressure) - (glomerular osmotic pressure + capsular hydrostatic pressure )
Can you mechanistically describe the functions of ADH, aldosterone, PTH, calcitriol and thiazides on the DCT? Thiazide
Na+/Cl- symporter inhibited, tubular fluid does not bring as much Na+/Cl- into the blood. If solute stays in the tubular fluid, water stays in the tubular fluid. More water stays in the collecting duct and more water is excreted from the body. Treats high BP
What is the smallest structural and functional unit of the kidney? How many are there per kidney?
Nephron (look like a tube) ~1 million.
The majority (60 - 70%) of water is reabsorbed from the filtrate in the________of the nephron.
PCT
Can you mechanistically describe the functions of ADH, aldosterone, PTH, calcitriol and thiazides on the DCT? PTH
PTH enhances the synthesis of all transporters within the distal convoluted tubule where it activates calcium absorption.
what are the functions of the vasa recta?
Peritubular capillaries are responsible reabsorption of tubular fluid and secretion of solutes into the tubular fluid. Vasa recta prevent the solute gradient created in the renal medulla from being washed out (i.e., diluted). surround loop of henle in juxtamedullary nephron
What is polyuria?
Production of abnormally large volumes of dilute urine.
What renal processes occur in the PCT?
Proximal Convoluted Tubule (PCT) - 60-70% reabsorption of sodium and water, 100% reabsorption of glucose and amino acids, and of ions (ammonium, H+, and HCO3) drugs and secretion of toxins caffeine and theophylline cause diuresis by enhancing Na+ and H2O excretion.
Can you diagrammatically describe the vasculature associated with a nephron?
Renal artery ---> segmental artery---> interlobar artery---> arcuate artery---> interlobar artery---> afferent arteriole ---->glomerulus---> efferent arteriole --->peritubular capillaries --->interlobar vein---> arcuate vein---> interlobar vein---> segmental vein --->renal vein.
Select both the transporter protein and the method of transport for reabsorption of glucose in the nephron.
SGLT
Sodium-potassium pumps vs Na+/Cl- symporter
Sodium-potassium pumps on side of epithelium closest to blood vessels (moving Na+ into blood) while Na+/Cl- symporter closer on the side of epithelium closest to tubular fluid.
Can you describe the structure and location of the juxtaglomerular (JG) apparatus?
The JG apparatus is a specialized structure formed by modified distal convoluted tubule cells and modified smooth muscle cells of the afferent arteriole. can sense low O2- trigger EPO production (chemoreceptor) can sense blood pressure- trigger renin production (mechanoreceptor)
What is the NKCC2?
The Na-K-Cl cotransporter (NKCC) is a protein that aids in the active transport of sodium, potassium, and chloride into and out of cells.
What is filtered by the glomerulus into Bowman's space?
The blood plasma is filtered through the capillaries of the glomerulus into the capsule. The Bowman's capsule empties the filtrate into the proximal tubule that is also part of the duct system of the nephron. A glomerulus receives its blood supply from an afferent arteriole of the renal circulation.
Can you explain, in detail, the determinant of glomerular filtration pressure (GFP) (i.e., explain the Starling forces of the glomerulus)?
The forces that favor filtration (movement out of the glomerulus and into Bowman's space) are glomerular hydrostatic pressure (which is essentially blood pressure in the glomerulus; 60 mmHg) and capsular osmotic pressure (which is negligible; 0 mmHg). The forces that favor reabsorption (movement out of the Bowman's space and back into the glomerulus) are glomerular osmotic pressure (which is primarily as the result of plasma albumin; 29 mmHg) and capsular hydrostatic pressure (15 mmHg). If you subtract the forces favoring reabsorption from the forces favoring filtration, you end up with the effective filtration pressure, 16 mmHg.
Can you list the components of the glomerular filtration membrane and describe its anatomical organization?
The glomerular capillary endothelial cells, the glomerular filtration membrane and the filtration slits (podocyte pedicels) between the podocytes perform the filtration function of the glomerulus, separating the blood in the capillaries from the filtrate that forms in Bowman's capsule. The glomerular filtration membrane is a fusion of the endothelial cell and podocyte basal laminas.
What remains behind in the blood after glomerulus filters it?
The glomerulus filters proteins and cells (i.e., does not let them pass), which are too large to pass through the membrane channels of this specialized component, from the blood. These large particles remain in the blood vessels of the glomerulus, which join with other blood vessels so that the proteins remain circulating in the blood throughout the body. The small particles like ions, nutrients and nitrogenous wastes pass through the membranes of the glomerulus into Bowman's capsule. These smaller components then enter the membrane-enclosed tubule in essentially the same concentrations as they have in the blood. Hence, the fluid entering the tubule is identical to the blood, except that it contains no proteins or cells.
How much plasma is filtered per day? How much plasma is reabsorbed per day? How much urine is formed per day?
The heart pumps about 5 L blood per min under resting conditions. Approximately 20 percent or one liter enters the kidneys to be filtered. On average, this liter results in the production of about 125 mL/min filtrate produced in men (range of 90 to 140 mL/min) and 105 mL/min filtrate produced in women (range of 80 to 125 mL/min). This amount equates to a volume of about 180 L/day in men and 150 L/day in women. Ninety-nine percent of this filtrate is returned to the circulation by reabsorption so that only about 1-2 liters of urine are produced per day.
Can you draw and identify the different regions of the loop of Henle?
The loop of Henle forms a hair-pin structure that dips down into the medulla. It contains four segments: the pars recta (the straight descending limb of proximal tubule), the thin descending limb, the thin ascending limb, and the thick ascending limb. The turn of the loop of Henle usually occurs in the thin segment within the medulla, and the tubule then ascends toward the cortex parallel to the descending limb. The end of the loop of Henle becomes the distal convoluted tubule near its original glomerulus. The loops of Henle run in parallel to capillary loops known as the vasa recta. Recall that the loop of Henle serves to create high osmotic pressure in the renal medulla via the counter-current multiplier system. Such high osmotic pressure is important for the reabsorption of water in the later segments of the renal tubule.
Can you explain, in detail, how the loop of Henle and the vasa recta work in concert to generate solute in the medulla of the kidney (i.e., countercurrent multiplication)?
The movement of fluid through the tubules causes the hyperosmotic fluid to move further down the loop. Repeating many cycles causes fluid to be near isosmolar at the top of Henle's loop and very concentrated at the bottom of the loop. Interestingly, animals with a need for very concentrated urine (such as desert animals) have very long loops of Henle to create a very large osmotic gradient. Animals that have abundant water on the other hand (such as beavers) have very short loops. The vasa recta have a similar loop shape so that the gradient does not dissipate into the plasma. The mechanism of counter current multiplication works together with the vasa recta's counter current exchange to prevent the wash out of salts and maintain a high osmolarity at the inner medulla.
Can you describe the organization of a renal corpuscle?
The renal corpuscle consists a fenestrated capillary bed (glomerulus) surrounded by a double-walled capsule (Bowman's capsule). Visceral lining of Bowmans: Podocytes have finger like projections that wrap around capillaries and interdigitate, forming slits between pedestals (filtration slit diaphragm)- makes it more selective
Loop diuretics carry out their pharmaceutical action at which portion of the nephron?
Thick ascending limb of the loop of Henle (furosemide that inhibits NKCC2)
What is its function? NKCC2
Transport sodium, potassium, and chloride into and out of cells through the loop of Henle. 2 Cl-, 1 K+, 1 Na+ into the epithelial cells in order for them to be to transported later via primary transported to peritubular fluid (medullary tissue) It is not a pump, it is a symporter that uses secondary transport
What is tubular absorption? What is its purpose?
Tubular reabsorption is the process by which water and solutes (e.g., glucose, amino acids, fatty acids) are moved from the tubular fluid back into the circulating blood. Since filtration is only a selective process based on size, the purpose of reabsorption is to reabsorb all of the water, ions and nutrients lost during filtration.
What is tubular secretion? What is its purpose?
Tubular secretion is the transfer of materials from peritubular capillaries to the renal tubular lumen and occurs by active transport and passive diffusion. Its purpose is the opposite process of reabsorption. This secretion is thought of as a "back-up" to filtration, and typically involves the removal of waste products and toxins not removed via the filtration process. movement from peritubular capillary (blood) to peritubular fluid to renal tubule (with wastes).
Can you describe the anatomical organization of the urinary system?
Two kidneys, two ureters, urinary bladder and urethra. Hilus area on kidney- have renal veins and arteries
ADH
binds to collecting duct cells and makes it permeable (aquaporins open) to water in order to reabsorb the water into the medullary tissue
Which of the following best explains how loop diuretics (like furosemide) work?
blocks NKCC2 symporters resulting in decreased solute reabsorption (and thus water reabsorption) leading to increased urine volume
the release of wastes from the body
excretion
Which type of capillaries make up the glomerulus?
fenestrated
What is the term given to the fluid that has entered Bowman's capsule and will run through the length of the nephron?
glomerular filtrate
the movement of plasma and dissolved solutes from the blood into Bowman's capsule
glomerular filtration
The forces that favor filtration (movement out of the glomerulus and into Bowman's space) are
glomerular hydrostatic pressure (which is essentially blood pressure in the glomerulus; 60 mmHg) and capsular osmotic pressure (which is negligible; 0 mmHg). capsular osmotic pressure: no solute in tube of nephron
The forces that favor reabsorption (movement out of the Bowman's space and back into the glomerulus) are
glomerular osmotic pressure (which is primarily as the result of plasma albumin; 29 mmHg) and capsular hydrostatic pressure (15 mmHg). glomerular osmotic pressure: solute in the glomerulus that are drawing water into blood (huge draw)
daibetes and polyuria
glucose dumped in urine and travels through nephron and does not reabsorb, high concretions of glucose bring water with it so the urine is diluted. Causes low BP which can cause death eventually (drop in blood volume)
concretion gradient of solute (urea and salt) is______as you move deeper into the medulla
higher This why is it called countercurrent multiplication
vasa recta
it is a blood vessel around the loop of henle helps keep salt pumped out from the ascending limb to remain in the interstitial fluid and the water pumped out from the descending limb to be removed do not want it to keep going down because it would wash out the concentration, but because it is in a "hair pin" structure it retains that concentration in the medullary tissue between the ascending and descending limbs. Therefore, with the two "hair pin" structures (versa recta and loop of henle), it is easier to maintain a high concretion of solutes (salt and urea) in the medullar tissue. The hairpin turns slow the rate of blood flow, which helps maintain the osmotic gradient required for water reabsorption
What drugs are designed to inhibit it? NKCC2
loop diuretics (e.g., furosemide) inhibit the NKCC2 at the TAL causes loss of water if they have high BP
during tubular absorption
movement of fluid goes from tubular fluid (actual nephron) to peritubular fluid (space surrounding it). Peritubular fluid will eventually flow into peritublar capillary (and into the blood stream)
K+ sparing diuretics
must be careful to not lose too much K+ ions in the urine due to typical diuretics antagonize aldosterone (e.g. spironolactone) or ENaCs (e.g., amiloride), saves K+ from being lost, and is still an effective diuretic
Which of the following is the principal functional unit of the kidney?
nephron
the movement of important filtered solutes (like nutrients) back into the capillaries
tubular reabsorption
the active movement of solutes from the capillaries into the nephron
tubular secretion
The kidneys are connected to the bladder via two ___________, down which, urine travels.
ureters