The kidney is unique because it has TWO capillary beds. Name them AND....what are they seperated by?????
Glomerular
Peritubular
Seperated by the efferent arterioles
How do the kidney's control homeostasis (in terms of hydrostatic pressure)
Kidney can control hydrostatic pressure in both sets of capillaries by altering resistance that will change GFR and/or tubular absorption
How many nephrons are there ?
1million/kidney
What does the nephron itself contain?
Nephron itself consists of the Glomerulus (Bowman's capsule and capillary supply) and long tubule divided into parts (PCT, LoH, DCT, & collecting ducts)
What is the renal corpuscule??
Glomerulus + bowman’s capsule which is where the urine essentially gets filtered from the glomerular capillaries and goes into Bowman’s capsule and then goes into the tubules.
The glomerular capillaries have hydrostatic pressure of about _______ (fairly high)
60mmHg
Where is the proximal tubule in the kidney?
cortex of the kidney
Where is the loop of Henle located in the kidney?
In the medulla
Describe how the filtrate goes from one of the nephron to the other
What is the difference between the cortical and the juxtamedullary nephrons?
Same parts but difference in how deep the Loop of Henle goes into the medulla of the kidney
Where is the coritcal nephrons loop of Henle?
Short Loop of Henle so it only goes a little way into the medulla
__-__% of nephrons are the juxtamedullary nephrons
20-30%
Which have longer loops of Henle the cortical or the juxtamedullary nephrons?
Juxtamedullary nephrons have much longer loops of Henle compared to the cortical nephrons
Where do the juxtamedullary nephrons lie in the kidney?
The renal corpuscle (glomerulus and bowmans capsule) lies in the deepest part of the cortex and much further into the medulla.
Which nephrons are really important for generating an osmotic gradient in medulla and that becomes responsible for water reabsorption???
juxtamedullary nephrons-create dilute or concentration urine depending on our needs for homeostasis
What is different about the blood supply to the juxtamedullary nephrons?
They have long efferent arterioles.
These go down into the outer medulla and divide into special peritubular capillaries. Essentially wrap around the tubules (peritubules)
the ones
What is the vasa recta ?
With the juxtamedullary nephrons ---Specialized peritubular capillaries that lie SBS with the loop of Henle
**becomes important when we talk about producing a concentrated urine.
Most capillaries have two layers but the glomerular capillary has 3 layers. What are they??
endothelium, basement membrane and the EPITHELIUM
What is another name for the epithelium of the glomerular capillary?
podocytes
What is the puprose of having more layers in the glomerular capillary?
The purpose of the 3 layers is that it can filter more water and solutes than the usual 2 layer capillary membrane can
What is special about the Endothelium of the glomerular capillary? (two things!)
Endothelium itself is perforated by a lot of small holes (Fenestrae) looks like swiss cheese.
Freely permeable to everything the blood except cells and plasma proteins (WBC, RBC, plasma proteins, and plts).
Plasma proteins are large so don’t’ pass easily and they HAVE A NEGATIVE CHARGE and so does the endothelial cells.
So the charges repel so for that reason as well as the size, proteins won’t pass.
Describe the basement membrane of the glomerular capillary
Gel like mesh.
Large spaces so water and solutes can pass through the space (think kitchen sponge).
Also has a negative charge so the proteins don’t go through.
Epithelial layer of glomerular capillary rests on basement membrane and lines the outer surface of the glomerular capillary. Describe this layer
Cells aren’t really continuous, Slit pores, cells are separated so slit in between, which permits large volumes of fluid to go from the capillaries into bowman’s capsule.
Again proteins don’t go.
What are the Mesangial cells? What do they do???
They act as phagocytes (Take foreign trapped material from basement membrane and get rid of it)
They also have myofilaments, can contract and essentially change the surface area.
Are the Mesangial cells part of a layer in the glomerular capillary?
No, these are found between and within the loops of the glomerular capillaries.
They aren’t a layer.
Name the 8 functions of the kidney and their role in homeostasis
1. Excretion of metabolic waste products
2. Regulation of water & electrolytes
3. Regulation of osmolarity (loop of Henle and vasa recta)
4. Regulation of acid-base
5. Regulation of BP – renin (juxtamedullar apparatus involved)
6. Secretion, metabolism, & excretion of hormones erythropoietin to stimulate RBC production
7. Gluconeogenesis
8. Activation of vitamin D
Glomerular filtration means what???
means filtering of plasma like fluid through glomerular capillaries into renal tubular fluid via bowman's capsule.
Blood-->urine
Why, in general, is the concentration of substance in the plasma is the same of the concentration of those substances in the glomerular filtrate?
Most substance in the plasma (except proteins and cells) go through glomerular filtration system into the Bowman's capsule.
Then what happens is as filtrate goes through the tubules both the volume of the fluid is reduced and the composition is altered by processes of tubular reabsorption
Substances go back into blood through the peritibular capillaries. Or it goes the other way, tubular secretion, meaning things that are usually actively secreted from the blood to the fluid for excretion.
Excretion =???? (equation)
Excretion = Filtration - reabsorption + secretion
Quantitatively, which is more important, reabsorption or secretion??
If we’re looking at quantitatively, reabsorption is more important than secretion
What substances is secretion important for??
Secretion is important for H+ and K+ secretion /excretion.
What is the real goal of glomerular filtration?
To eliminate the waste products we want to get rid of while at same time retaining water and important electrolytes.
How we have ideal composition of all ECF (is through these processes)
What is filtered in glomerular filtration?
Waste products of metabolism
Hormone metabolites
Electrolytes (mostly reabsorbed)
Amino acids (reabsorbed-mostly)
Glucose (reabsorbed-mostly)
What are the following waste products from?
Urea
Creatinine
Uric acid
Bilirubin
Urea – from amino acids
Creatinine – from muscle creatine
Uric acid – from nucleic acids
Bilirubin – from hemoglobin
When does glucose spill into the urine?
When it's above the threshold
Glucose level must be below the renal threshold (if blood glucose level is below a certain point it won’t spill in the urine)
TRUE or FALSE. Waste products are usually reabsorbed
FALSE
Waste products are generally poorly reabsorbed.
What is the composition of the glomerular filtrate??
Like plasma but without plasma proteins & cells.
Remember protein bound things (like Ca+) are not filtrated when bound!
GFR = ___L/day or ___ml/min
180L/day or 125ml/min
GFR generally correlates with what??? (hint: it's about 10% less in women)
generally correlating w/surface area for filtration (About 10% less in women)
What is renal artery pressure and renal vein pressure (usually)
Renal artery arterial pressure is essentially = Systemic arterial pressure.
Renal vein pressure is about 3-4mmHg.
Resistance is a big factor in renal blood flow. What controls resistance?
Resistance is controlled by sympathetic NS & hormones.
So an increase in resistance will reduce renal blood flow and vice versa as long as arterial and venous pressures are constant.
How is autoregulation important in regards to renal blood flow?
Autoregulation is impt here and over the range of arterial pressures (80-170mmHg) renal blood flow and GFR will remain constant (MAP)
Renal blood flow is about __% of CO even though kidneys are about less than __% of Body weight.
20%; 1%
Why is renal blood flow is 10x more than required?
reason is for kidneys to be able to eliminate waste products.
How does SNS cause an increase in GFR even though there is vasoconstriction of the afferent and efferent arterioles?
SNS activity will cause increased glomerular capillary hydrostatic pressure. We know that if SNS activity increases BP, it will also increase glomerular capillary hydrostatic pressure.So even though SNS stimulation will cause afferent and efferent vasoconstriction and therefore decrease glomerular filtration, that vasoconstriction will also increase glomerular capillary hydrostatic pressure (which favors filtration). The net result of these two things that are, in a sense, working in opposition is that GFR will decrease from SNS stimulation, but not as much as you would expect from the vasoconstriction alone
Mild to moderate SNS stimulation has little effect on GFR except when???
Translates to mild-mod SNS stimulation has little effect but more significant in setting of acute blood loss and SNS stimulation (would have more of an effect on GFR).
As long as renal blood flow doesn’t fall below ___% of normal, acute RF can be reversed as long as the cause of the ischemia is corrected before there is cellular damage
20
Describe the hormonal control of renal blood flow that cause Vasoconstriction
Epi and Norepi: cause vasoconstriction of afferent and efferent arterioles, decrease RBF and decreased GFR.
Endothelin: (from damaged endothelial cells is potent vasoconstrictor)
Angiotensin II: works preferentially on the efferent arteriole and contributes to autoregulation
Renin: Secretion stimulated by SNS activity=Vasoconstriction
Describe the hormonal control of renal blood flow that cause Vasodilation
Atrial Natriuretic Peptide : vasodilator. Produced in atrial cells of the heart. ↑ glomerular hydrostatic pressure → ↑ GFR
Prostaglandins & bradykinin : vasodilators→ ↑ GFR
Nitric oxide : vasodilator →↑ GFR
Describe what stimulates Renin secretion
Juxtaglomerular apparatus is the site of secretion of renin.
If there is a decrease in RBF caused by SNS activity, that will also decreased flow of Na and Cl to macula densa which stimulate renin release and get RAAS and vasoconstriction from AII.
What is the definition of Renal Autoregulation?
Renal blood flow & GFR relatively constant despite changes in BP
What is the purpose of Renal Autoregulation?
Maintain oxygen & nutrient delivery
Removal of waste products
--Maintain constant GFR & control of water & solute excretion
What is the mechanism of autoregulation?
Feedback linking changes in [NaCl] at macula densa with control of arteriolar resistance
What does the macula densa do?
These cells will sense the changes in volume that get delivered from the thick ascending limb to the distal tubule.
The signal from the macula dense has 2 effects:
It will decrease the resistance in the afferent arterioles which will increase glomerular hydrostatic pressure, helping returning GFR back to normal.
An increase in renin that is released in the RAAS (renin angiotensin aldosterone system).
What stimulates the tubuloglomerular feedback mechanism?
↓ GFR → ↓ flow via L of H → ↓ NaCl concentration at macular densa (↑ reabsorption)
What effects does the tubuloglomerular have when stimulated?
↓ resistance of afferent arterioles→ ↑ glomerular hydrostatic pressure ↑ GFR to normal
↑ renin →↑ angiotensin I → ↑ angiotensin II → vasoconstriction of efferent arterioles →↑ glomerular hydrostatic pressure returning GFR to normal
What is the point of the tubuloglomerular feedback mechanism?
It provides feedback to both the afferent & efferent arterioles for autoregulation of GFR.
As long as the MAP is 75 or 80 – 160 or 170 [then GFR will change minimally.
What is the myogenic mechanism?
Another piece of autoregulation (besides tubuloglomerular feedback)
Smooth muscle of afferent arterioles contracts in response to stretching produced by an ↑ transmural pressure
↑ Perfusion pressure → ↑ contraction & ↑ resistance, results in decreased flow and GFR returns to normal
Outside of autoregulation, renal blood flow is .....
pressure-dependent
Glomerular filtration generally stops when the MAP is <__-___mmHg (according to Morgan).
40-50
Glomerular Capillary Hydrostatic Pressure (GCHP) is a factor effecting GFR. What are the three variables that determine the GCHP?
Systemic BP
Afferent arteriolar tone (Vasoconstriction& Vasodilation)
Efferent arteriolar tone (Vasoconstriction & Vasodilation)
What is the main means of physiologic regulation of GFR??
Glomerular Capillary Hydrostatic Pressure
If we increase resistance in afferent arterioles (constrict) will it increase or decrease glomerular capillary hydrostatic pressure?
DECREASE it, so decrease GFR
Dilation of afferent arterioles will do the opposite, increase GCHP and increase GFR
What happens to the glomerular capillary hydrostatic pressure if we constrict the efferent arterioles?
Increase GCHP and increase GFR
Vasodilation will do the opposite (Decrease GCHP and decrease GFR)
***But only to a point....
If we constrict the efferent arteriole, that will increase resistance to outflow. That also increases GCHP and will increase GFR to a point, the point being as long as that constriction of efferent arteriole doesn’t back up and decrease Renal blood flow too much. What happens then?
Severe efferent constriction causes a decrease in renal blood flow in that way, causes increase in the filtration fraction because of the decreased denominator of that filtration fraction.
So w/severe constriction of efferent arteriole there is a decrease in GFR. (but up until severe there would be an increase in GFR)
Bowman’s Capsule Hydrostatic Pressure is another factor affecting GFR. What happens if this pressure increases? (what scenario may this happen??)
Increasing BCHP = decreased GFR (Pushing back into the glomerulus)
Glomerular capillary osmotic pressure is another factor effecting GFR. How does it do this?
Increased Glomerular capillary osmotic pressure (meaning an increase in plasma protein concentration) that will pull back more into the glomerular capillaries and will oppose filtration and because the glomerular capillary osmotic pressure follows plasma colloid osmotic pressure if there's a decrease in plasma colloid (or plasma protein concentration) that will increase filtration because there will be less opposition to filtration
Ex: ↑Albumin =↓filtration
Changes in filtration coefficient is another factor that will effect GFR. How?
↑ filtration coefficient → ↑ GFR \GFR is directly proportional to membrane permeability & surface area
Contraction of mesengial cells (from angiotensin 2, vasopressin, norepi, & histamine but NOT dopamine) ↓’s surface area → ↓ GFR
HTN, DM, etc. also ↓ effective surface area from thickening of glomerular capillary membrane so ↓ GFR
List some conditions that may alter GFR
Chronic, uncontrolled HTN
IDDM
Kidney stones
Hypotension
Renal artery stenosis
ACE inhibitors
Sympathetic stimulation
How does long term uncontrolled HTN alter GFR?
Kf permeability coefficient will decrease because of thickness of glomerular capillary membrane, damaged capillary, loss of functioning, loss of surface area for filtration, decreased GFR
How do kidney stones effect GFR?
cause increase in hydrostatic pressure in Bowman’s capsule obstructing outflow. So for that reason decreased GFR.
How does renal artery stenosis alter GFR?
afferent arteriole constriction, so decreased glomerular capillary hydrostatic pressure and decreased GFR
How doe ACE-I alter GFR?
they’ll be a decrease in efferent arteriolar resistance (Angiontensin II preferentially causes vasoconstriction of efferent arteriole) so if we’re inhibiting that effect with an ACE-I or ARB we get less efferent arteriolar resistance, decreased glomerular capillary hydrostatic pressure and decreased GFR. So patients on ACE-I need renal function (GFR) followed.
How does sympathetic stimulation alter GFR?
similar to renal artery stenosis, increased in afferent arteriolar resistance, decreased glomerular capillary hydrostatic pressure and decreased GFR.
TRUE or FALSE. Tubular reabsorption isn't selective & quantitatively small
FALSE. Tubular reabsorption is selective & quantitatively large
How does reabsorption occur?
Active transport
Co-transport with sodium (Glucose, Amino acids, &Organic acids)
Osmosis (water)
Tubular secretion important for which two things?
H+ and K+
Where does reabsorption and secretion occur?
In the tubules
What two things are completely reabsorbed (unless over threshold) so they are not excreted (essentially excretion is zero)
Glucose and AA
What is poorly reabsorbed and are mainly excreted ?? (Which is a good thing)
Certain waste products (urea, creatinine)
What is highly reabsorbed but the rates of reabsorption and secretions of some ions can be variable and can be controlled
many ions (esp. Na+)
Describe the active transport in reabsorption
Na is actively transported by the Na/K ATPase pump.
This pump keeps a low intracellular gradient so the Na+ will go passively from the tubular lumen into the epithelial cells.
So the active transport sets up the intracellular gradient for passive transport of Na from the tubular lumen
Describe co-transport in reabsorption
Na+ gets coupled w/other solutes.
Also coupled w/secretion of H+ ions.
If Na and other substances (like glucose, AA, etc.) going from tubular fluid back into circulation (reabsorbed) but for something like H+ going in opposite direction.
Co transport(going in same direction-reabsorption) vs. counter transport (going in opposite direction- H+ secreted while Na is reabsorbed)
What is a major function of the proximal convoluted tubule?
Na+ reabsorption (2/3 of it happens here)
What two things will enhance Na reabsorption in the PCT?
Angiotensin II and norepi will enhance NA reabsorption in early PCT
Only about __-__% of glomerular filtrate actually gets to the Loop of Henle because so much gets reabsorbed in the PCT
25-35%
Describe the pathway of Na through primary active transport
Na – K – ATPase system moves Na from tubular epithelial cell → across basement membrane to interstitial fluid to the peritubular capillary
Negative potential inside the epithelial cell & concentration gradient cause diffusion of Na from tubular fluid into tubular epithelial cells (where it gets actively transported again)
Describe facilitated diffusion of Na+ reabsorption
Carrier proteins on luminal surface of epithelial cell membrane
↑ surface area in proximal tubule
Describe the glucose secondary active transport
Na+ diffuses down concentration gradient created by Na-K-ATPase pump
Energy is released which then drives the transport of substance glucose against concentration gradient
So essentially all glucose and all AA are reabsorbed in this way.
How is water reabsorbed? Does it require energy?
Passive by osmosis, no ATP required
Describe the "solvent" drag associated with water reabsorption
Water often moves w/Na.
As water moves across those junctions by osmosis it can carry solutes with it.
So changes in sodium reabsorption significantly influences reabsorption of sodium and other solutes.
TRUE or FALSE. Water can only move if the membrane is permeable to it, regardless of concentration gradient
TRUE
Water moves through “tight junctions” but the permeability of these varies according to section of tubule. Describe each section and the permeability
PCT: highly permeable to water and ions.
Ascending loop of henle: in particular almost no water is reabsorbed, essentially impermeable to water despite a concentration gradient.
DCT and collecting ducts: permeability of water is dependent of ADH and insertion of aquaporins so water can get reabsorbed
What receives filtrate from Bowman’s capsule?
Proximal Convoluted Tubule
The proximal convoluted tubule reabsorbs ___% of Na+ and water (most of it)
65%
Why does the proximal convoluted tubule have a high capacity for active and passive reabsorption?
because of the quality of tubular epithelial cells. Will also secrete organic acids, H+ and bases as well as bile salts, catecholamines as well.
-Many mitochondria (suited to active transport)
-Large surface area
-Multiple carrier proteins
Describe the thin descending portion of the loop of Henle
Very permeable to water
Mod permeable to solutes
Simple diffusion
What are the three sections of the Loop of Henle?
Thin descending
Think ascending
Thick ascending
Which part of the loop of Henle is Impermeable to water -** key to concentration of urine
The ascending portion (both thin and thick)
Why is there not much active reabsorption in the descending limb of the loop of henle
few mitochondria
What is different about the thick ascending loop of henle?
Highly metabolic (Na-K-ATPase pump)
Solute reabsorption (will reabsorb about 25% of filtered Na, Cl, K as well as large amount of Ca bicarb and Mg.)
In the thick ascending limb of the loop of Henle, reabsorption of about __% of filtered Na, Cl, K as well as large amount of Ca bicarb and Mg happens.
25%
Where is the Loop diuretic site of action??
in the THICK ASCENDING loop of Henle
Where is the Juxtaglomerular complex?
In the distal tubule
Why is the distal tubule called the diluting segment? (hint for studying: Distal = Diluting)
Reabsorbs most ions!
5% of filtered sodium
Na-Cl co-transporter
Impermeable to water
Where is the Thiazide diuretic site of action?
The distal tubule
What do the principal cells in the late distal and cortical collecting duct do?
Reabsorb Na+ & water and secrete K+
Aldosterone mediated
Where is the K+ sparing diuretic site of action?
Late distal and cortical collecting ducts (the principal cells)
What do the Intercalated cells of the late distal tubule and cortical collecting duct do?
reabsorb K+ and bicarbonate & secrete H+
Permeability to water in the late distal tubule and cortical collecting duct is controlled by....
by ADH
Where is the final site for processing urine?
Medullary Collecting Duct
How is the permeability to water controlled in the medullary collecting duct?
by ADH
What is a "bit unusual" about the medullary collecting duct?
Permeable to urea
unique because urea can get reabsorbed which increases the osmolarity of the interstitial fluid in the medulla which becomes important in making a concentrated urine
How is the medullary collecting duct important in acid/base balance?
Secretes H+ against a concentration gradient
Regulation of Tubular Reabsorption is done by Peritubular capillary vs interstitial forces. Describe this
Hydrostatic – related to arterial BP
↑ BP → ↓ reabsorption
Colloid osmotic – related to plasma colloid osmotic pressure
↑ plasma proteins → ↑ COP → ↑ reabsorption
↑ filtration fraction → ↑ plasma filtered → ↑ protein in remaining plasma → ↑ COP → ↑ reabsorption
