Test 5 🤠 Flashcards
What are 2 major functions of the cardiovascular system?
-Transporting nutrients to tissues
-Transporting waste product away from tissue
How does the CV get messages to other parts of the body?
Transports hormones for signaling
Which system is responsible for putting hormones into the vascular system?
Endocrine System–CV system then delivers the hormones to where they needs to go
What is a typical measurement for volume?
L, mL, ,Gal
What is velocity measuring?
Units of distance/ Time
m/s or km/hr
What does pressure measure?
How much force do you need to drive a column of Hg up 1mm
How is pressure measured in CV system?
mmHg
How is pressure measured in the lungs?
cmH2O
What does cross-sectional area measure?
Area within the center of a tube
internal diameter of a cylinder
What is surface area?
Walls of a cylander
Would a large cylinder have a lot or a little surface area?
Large cylinder has lots of surface area
What are the units for blood flow?
Volume/ Time
-mL/min
-L/min
-mL/sec
What are 3 of the important determinants of blood flow discussed in class?
-Vascular resistance
-Vasular conductance
-Poiseulle’s Law
What happens to blood flow with increased vascular resistance at a tissue bed?
More difficult for blood to flow
Do we want high vascular resistance or low vascular resistance?
Lower vascular resistance to allow for greater blood flow
What does vascular resistance determine in the body?
Blood pressure–how much pressure we have
What would you expect the pressure to be between the heart and an area of high resistance distal?
High pressure–measuring upstream of constricted spot is higher pressure
What would the pressure be below a high pressure constricted spot in a vessel?
Lower pressure–downstream of constriction is lower pressure
What is pressure used for in the body?
Used to drive flow
What is an example of the body using pressure to drive flow?
Brain uses CPP to drive brain blood flow–changes based on vascular resistance in the body
What is vascular conductance?
How easy it is to drive some type of flow through a conduit
Inverse of vascular resistance
If a vessel is easy to drive blood flow through, what would the conductance be?
High vascular conductance
If a vessel is difficult to drive blood flow through, what is the conductance?
Low vascular conductance
What is Poiseulle’s Law?
Includes other variables to make sense of vascular resistance and pressures
Where is most of the blood in our body stored?
The veins
What is adequate cardiac output dependent on?
A system where blood in the veins can make it back to the heart
Which organ controls how much fluid is in our body?
The kidney
Why is fluid in the body important?
Fluid in the body is directly related to how much blood we have
What happens to blood volume if the kidney holds on to more fluid?
Blood volume increases
What are 2 important functions of the kidney?
-Important controller of overall volume in CV system
-Filter
What are 2 different ways the CV system blood vessels can be constructed?
-System in Series
-System in Parallel
How are system in series set up?
Connect vessels from end to end to make one long tube
What happens to resistance with system in series?
Resistance in the 2 individual tubes doubles when they are stacked together length wise
Why does resistance increase when vessels are stacked length wise?
Harder to pump blood through a longer tube
How are systems in parallel set up?
increased number tubes of the same size, length, and resistance
creates more pathways for blood to flow
What happens to resistance in systems in parallel?
Blood has options on where to flow–increased pathways lowers resistance
What type of system of blood vessels is in the kidney?
Has both system in series and system in parallel
What is the formula for series system?
Rtotal= R1 + R2 + R3
What is the formula for parallel system?
1/R total= (1/R1) + (1/R2) + (1/R3)
What is the internal diameter of the aorta?
2.5 cm
How does the cross sectional area of the aorta compare to small arteries in the body?
Other arteries have small internal diameter–but there are more of them in the body
total cross sectional diameter of all the arteries is larger than aorta because there are more
What is the cross sectional area of small arteries?
20cm^2
How does total cross sectional area of capillaries compare to arteries?
More capillaries than arteries, so cross sectional area of capillaries is bigger than arteries
What is the total cross sectional area of capillaries?
2500 cm^2
What is blood flow speed dependent on?
Cross sectional area of specific spot in the circulation
What is the velocity of blood flow in a small cross sectional area?
Decreased path for blood to flow through
Blood will flow quickly if only one small tube for the blood to move through
What happens to total cross sectional area as blood travels further from the heart?
cross sectional area increases
What happens to blood velocity in areas with increase cross sectional area?
Velocity is lower because there are so many options for where the blood can flow
Why is blood flow through the capillaries slow if the cross sectional area of a single capillary is small?
Blood flow is slower because there are so many capillaries the blood has many different routes to take
What is the pressure like in the left atrium?
Low pressure
What is the pressure in the left ventricle and aorta?
High pressure
What happens to pressure with increased distance from the heart?
Further from the heart pressure will decrease
At what part in the circulatory system do we see a decrease in pressure?
Large arteries pressure is the same as aorta
Small arteries–pressure starts to decrease a little
further decrease pressure in arterioles
Blood has ___________ pressure as it flows through a conduit that has _____________ resistance.
reduced , high
What are the high resistance blood vessels in systemic circulation?
Small arteries and arterioles
What part of the vasculature does phenylephrine work on?
squeezes small arteries and arterioles
What happens to pressure proximal to the high resistance vessel when phenylephrine is given?
Pressure increases
What happens to pressure distal to the high resistance vessel when phenylephrine is given?
pressure is lower
What vessels determine blood pressure?
Small arteries and arterioles–resistance vessels
What is resistance like in the veins?
Not very much resistance
Thin walled and compliant
What is the pressure gradient between the end of capillaries and the right atrium?
10mmHG (very small amount)
What is needed to control blood flow?
Pressure
How does the kidney manage blood/fluid flow?
The kidney adjusts vascular resistance
What dictates blood flow?
Metabolic rate of the tissue
What needs to happen in the body if a tissue has a high metabolic rate?
Increase blood flow/volume to the tissue
What is laminar flow?
blood in the middle of the vessel flows faster than blood closer to the walls
Is laminar flow a good thing?
Yes, it is orderly flow–efficient and doesnt cause problems
Why does blood flow slow down the closer it is to the walls in laminar flow?
The walls of the vessel are resistance to the flow
What is it called when blood flow is disorderly?
Turbulent flow
What is happening with turbulent flow?
-Not efficient blood flow
-Movement of blood in all different direction
-blood runs into the walls of the vessel and causes remodeling over time
Why is turbulent flow so bad?
Blood runs into the walls of the vessel and causes remodeling over time–things will get stuck in the wall (CHO, Ca2+)
What initially causes turbulent flow?
Clot or blockage in the vessel
-Narrow opening for blood to go through–blood will shoot through opening (high velocity) and spray the other side of the obstruction
What is the Reynolds equation used for?
Predicts the odds that turbulent flow is going to occur
What are the “2 parts” of the heart circulatory system?
Right heart and left heart
How is each part of the heart circulatory system set up?
In parallel–lots of choices where to go (brain, coronaries, GI, kidney)
How much cardiac output goes to the kidneys?
22% (1100mL/min)
Why does the kidney require so much perfusion?
Kidneys have much more perfusion than they actually need–use extra blood flow to work as efficient filter
Does kidney blood flow correlate with metabolism?
only partially, only place in the body where flow doesnt correspond to metabolism
What can ultrasound of an artery measure?
blood flow
What is the resistance portion of ohms law in regards to electrical stuff?
Cell wall
How is Ohms law used in the CV system?
Swap some of the variable
delta BP= blood flow x vascular resistance
What does Delta Pressure measure?
The distance between one side of the tube and the other
What is flow represented by small delta P?
Less flow
What is the flow represented by a large delta P?
more flow
What small change can result in a large change in blood flow?
Blood vessel diameter
What happens to blood flow when a vessel relaxes a little bit?
Can account for a big increase in blood flow through the vessel
What happens to blood flow when a vessel constricts a little bit?
Can reduce flow by a lot
What is the formula for vascular resistance?
R= Delta P / Force
What is vascular resistance dependent on?
Delta P and blood flow of the organ
What is the BP in the renal artery?
100mmHg at abdominal aorta
What is BP in the renal vein?
0 (probably more like 10mmHg)
How to calculate blood flow in the kidney:
20% cardiac output–1100mL/min
What are capillary Starling Forces used for?
4 forces that determine whether fluid will move out of the blood into the interstitial space OR into the blood
Why is blood pressure low in the veins?
Veins are on the other side of the high vascular resistance
What happens to blood pressure as it move through an area of high resistance?
Blood pressure is reduced as the blood flows further through the area of resistance
What is systemic blood pressure usually measuring?
Blood pressure in the large arteries proximal to resistance
What does CVP measure?
Distal pressure
Where do we measure pressure in the kidneys?
Proximal and distal pressures
What causes the drop in pressure from large arteries to capillaries?
High vascular resistance as we move away from the heart
Where does a pressor work in the vasculature?
Constricts arterioles and drives up blood pressure
Which arteries are able to contract and why?
Smaller arteries can contract and relax–large arteries usually dont contract
What is filtration?
Movement of fluid out of the capillary
What part of the capillary has forces that factor filtration?
Arteriole end
What is reabsorption?
Fluid absorbed by the capillary–fluid moved back into the capillary
Where are the forces that favor reabsorption in the capillary?
At the venous end
How many capillaries do we have in our body?
10+ billion capillaries
How much surface area is made up of capillaries within the body?
500-700 square meters of surface area
What is the primary function of capillaries in the periphery?
Primary place for nutrient exchange and waste product collection in the circulation
What controls the blood flow through the capillaries?
Controlled by the arterioles
What allows for arterioles to regulate blood flow?
Smooth muscle cells packed into arterioles allows regulation of blood flow to tissues downstream of arterioles
How many layers of smooth muscle is there is small arteries and arterioles?
4 layers of thick smooth muscle
How do the capillaries function in gas exchange?
Offload O2 and pick up CO2 to carry to the lungs for removal
What is the total cross sectional area of the aorta?
4.5cm^2
What is the velocity like through the aorta?
High velocity–especially during systole (ejection)
How many vena cava?
2–inferior and superior
How do the vena cava internal openings compare to the aorta?
Each vena cavae has a slightly larger opening than the aorta
What is the internal diameter for each vena cava?
3cm
What is the cross sectional area for the vena cava?
multiply x2 since there are 2 vena cava it increases total cross sectional area that blood moves through
18cm^2
What is the velocity in the vena cava compared to aorta?
Lower velocity in both vena cavae since there is more cross sectional area for the blood to move through when returning to right atrium
What is the internal diameter of arterioles?
30mcg–very small
What composes arteriole walls?
Thick walls from lot of smooth muscle
high wall thickness to internal diameter ratio
What are capillary walls composed of?
very thin–one cell layer thick of endothelial cells
Where in the body are endothelial cells?
Inner layer of all heart chambers
One layer of endothelial cells in veins and arteries
Why cant capillaries contract?
No smooth muscle
Why is lack of smooth muscle and thin walls good in the capillaries?
Less to get in the way for nutrient exchange (inward or outward)
What is the cross sectional area of the capillaries?
4500cm^2
Order these vessels from lowest velocity to highest velocity: veins, aorta, capillaries
Capillaries, veins, aorta
What does delta P measure?
Tendency of fluid to move through a capillary
What is normal BP at arteriole end of systemic capillary?
30mmHg
What is normal BP at the venous end of the systemic capillary?
10mmHg
What is average aortic BP?
100mmHg
Why is it important to have a balanced system of filtration and reabsorption?
Prevents too much or too little fluid in the tissue
What are the forces that determine whether fluid will move out of the blood into the interstitial space or into the blood?
Capillary Starling Forces
What does “P” stand for?
Pressure
What is Pcap?
blood pressure in the capillary
Physical fluid pressure (hydraulic pressure) that exists in the blood in the capillary
What is Pcap at arteriole and venous end?
Arteriole: 30mmHg
venous: 10mmHg
What does Pcap determine?
How much fluid is forced outward through the capillary membrane
What are capillaries fairly permeable to?
Only one cell layer thick, permeable to water and small ions
What happens to resistance is there are forces in the capillary that are pushing fluid out of the capillary?
There will not be much resistance in the capillary beds
What is P(isf)?
Pressure in the ISF–outside the capillary and outside the cells
What is a normal ISF pressure?
-3mmHg
What is ISF pressure negative?
lymphatics operate to pull excess fluid out of the interstitium like a vacuum which pulls fluid from the capillary
What happens to reabsorption when lymphatics are pulling excess fluid out of interstitium?
more fluid movement out of the capillaries–Reduces amount of reabsorption at the venular end of the capillary
What does it mean if P(isf) is a positive number?
force fluid inward through capillary membrane
impairs filtration filtration at the arteriole end and promotes reabsorption at the venous end
What happens with a high positive pressure in the ISF?
could either oppose filtration or promote reabsorption if high enough
What would happen with fluid movement if P(isf) is +10mmHg?
Oppose fluid going into the capillary–reduce filtration and promote more reabsorption
How does fluid move when P(isf) is negative?
Forces fluid outward
What does p(cap) stand for?
Plasma oncotic pressure or Capillary colloid plasma oncotic pressure
How does fluid move with a normal p(cap)?
Causes osmosis of fluid inward through capillary membrane
How does p(cap) keep fluid inside the capillary?
All colloids dissolved in blood will hold fluid inside the capillary
What is the ideal plasma oncotic pressure in peripheral capillary for a healthy person?
28mmHg
What are the 3 main plasma proteins that make up plasma oncotic pressure?
Albumin
Globulins
Fibrinogen
What are globulins?
Antibodies, things generated by the immune system
What is fibrinogen?
Coagulation factor
What could happen that would lower plasma oncotic pressure?
Hemorrhage
What happens when plasma oncotic pressure is low?
difficult to keep the fluid within the CV system
lacking the colloids needed to keep the fluid there
What are examples of conditions that would cause plasma oncotic pressure to be low?
Hemorrhage
Capillaries become porous
What happens if the walls of the capillaries become more porous than normal?
colloid proteins can escape through the openings
once wall is permeable to proteins, the proteins not longer have as much osmotic pressure associated with them
What is osmotic pressure dependent on?
Semipermeable membrane where fluid can move but some dissolved substances cant
Is osmotic pressure affected if the capillary is porous but the proteins are still inside the capillary?
Yes. it creates a problem even before the colloids start leaking out
Even if protein are still in there capillary, they do not have osmotic pressure when the walls of the capillary are porous
What condition would cause porous capillaries?
Sepsis
If a patient is septic, why doesnt albumin solve the problem by replacing plasma proteins that are leaking out?
Primary issue is that the protein doesnt matter if the cell wall is already permeable to the proteins
secondary issue is the proteins leaking out
What does p(isf) stand for?
Interstitial fluid colloid osmotic pressure
What is p(isf) measuring?
Amount of proteins in the ISF
where are most proteins in the ISF?
Proteins in ISF are usually a matrix protein between cells
What are 2 common protein found in the ISF?
Proteoglycan Filaments
Hyaluronic Acid
What are Proteoglycan filaments?
large string of proteins in interstitial space
Why does hyaluronic acid stay in the interstitial space?
Large protein that cant move into capillary easily
How does osmotic pressure in ISF compare to capillary plasma pressure?
not as many proteins in ISF as in the CV system
What is a normal ISF osmotic pressure?
8mmHg
How does fluid move in response to ISF osmotic pressure?
causes a little movement of fluid outward through capillary membrane to ISF–usually outweighed by plasma oncotic pressure
What could cause elevated ISF colloid pressure?
Could be due to damage causing cells to burst (crush injury, bacterial infections)
or increased permeability in the capillaries
What is happening at the tissue with elevated ISF colloid pressure?
Causes swelling from all the proteins that were in the cell that are now in the environment
proteins in environment pull more fluid out from the capillary into the tissues
If there was increased permeability to the capillaries and proteins leak into ISF, what happens once the issue is fixed and the capillaries are intact again?
Swelling in the tissue stays even after the capillary is fixed–proteins still sitting in ISF with no way back into CV system
How can proteins get back into the plasma?
Lymphatics can slowly pick up the proteins–not specialized to do this so it takes a long time
What are lymphatics dependent on to function normally?
Lymphatics increase rate of action when skeletal muscle is active
What is the normal function of the lymphatic system?
specialized to get rid of excess fluid in ISF
lymphatics can increase work they are doing 20-40X normal is the body is working properly
Where are lymphatic capillaries located?
Near all tissues and capillaries
lymphatic system is a big circulatory system in the body–important to know topography of lymphatic circulatory system before surgery
What is K(f)?
Capillary filtration coefficient
What does K(f) measure?
capacity of the capillary membrane to filter water
measurement of capillary permeability and takes into account surface area
How does movement within a capillary change if the capillary expands (increases surface area)?
More surface area for movement which increases movement
What is the rate of fluid filtration in a tissue determined by?
The number and size of pores in each capillary
the number of capillaries
What system is responsible for collecting excess filtration?
Lymphatic circulation system
What are the areas of collection in lymphatic system?
Lymph nodes
Why drives venous blood flow?
Skeletal muscle activation from moving around
What drives lymphatic circulation?
Skeletal muscle activation from moving around
Why are venous and lymphatic systems so reliant on skeletal muscle to function?
Venous and lymphatic system is a one way valve
need skeletal muscle compressing and relaxing against them to get fluid moving in one direction
Where does lymphatic system return fluid to?
Back to CV system at the top of the chest (lymphatic ducts)
Where are the lymphatic ducts located and what is their purpose?
Located at the top of the thorax connect with large veins
entry point for lymphatic fluid to be returned to CV system
What speed does lymphatic flow normally flow at?
Flow is normally low–with increased activity lymphatic flow can increase up to 20X if needed
What happens to lymphatic system if someone if bed bound?
Not using skeletal muscles that are required for lymphatic to work at optimum level
excess fluid isnt being recollected as quickly as it should be
What happens to someone in regards to lymphatic system if they are in a hospital bed not walking around?
Fluid gets stuck in lower extremities
What can be used to simulate movement in the legs when someone is in the hospital bed bound?
SCDs–help with venous return, prevent clots, and important for lymphatic movement
What is net filtration pressure (NFP)?
Sum of the Starling Forces
What does it mean if net filtration pressure is positive?
There will be a net fluid filtration across the capillary (favors movement out of the capillary)
How is NFP calculated?
Add up components that favor movement out of the capillary starting at either arteriole or venous
Minus forces that is opposing filtration
What would NFP be at the arteriolar end of the capillary?
(30+3+8)-(28)= +13mmHg
Favor filtration
What does it mean if net filtration pressure is negative?
Net fluid absorption from the interstitial space into the capillaries
What would NFP be at the venous end of the capillary?
(10+3+8)-(28)= -7mmHg
Favors reabsorption (fluid moving into the capillary)
Why are the number of filtration and reabsorption in a capillary not equal/opposite to balance out?
Ends up being excess filtration compared to reabsorption
What happens to the excess filtration?
Extra fluid is scavenged by the lymphatic system
What forces in the capillary favor filtration?
arteriole/venous BP
ISF hydrostatic pressure
ISF oncotic pressure
What forces in the capillary favor reabsorption?
Plasma oncotic pressure
What would happen to tissues if lymphatic system wasnt working?
Excess fluid build up in the tissues from the excess filtration happening
What is net capillary pressure definition and value?
Average Capillary blood pressure in systemic circulation
17.3mmHg
Why is net capillary pressure not 20mmHg (directly in between 10 and 30)?
A lot of capillaries get larger in width when moving from front to end of the capillary
What is the typical net filtration pressure in the individual capillary?
0.3-there are so many capillaries it is highly dependent on getting excess fluid scavenged from ISF
What are some things that capillaries are permeable to?
Water
Sodium Chloride
What is the permeability of NaCl?
0.96
What is the specialized capillary bed that doesnt allow NaCl through?
Blood brain barrier
What type of molecules have a difficult time getting through the capillary wall?
Larger molecules (albumin, glucose)
What is the capillary permeability of albumin?
albumin is very large so low permeability: 0.001
What is the molecular weight of albumin?
69,000 (very large)
What is the capillary permeability of glucose?
0.6
Lower permeability than NaCl since glucose is larger
How does glucose get into the brain?
GLUT transporters
What is the blood pressure in the renal artery?
100mmHg
What is the blood pressure when the blood is exiting the kidney?
Blood encounters resistance in all the blood vessels in the kidney so but the time its exiting BP is really low
What does BP reduction in the kidney depend on?
amount of vascular resistance encountered
Why does blood pressure decrease in areas of vascular resistance?
Requires energy to be removed from the blood to move through a high resistance vessel
What is delta P in the kidney?
around 100mmHg
What lies in front of the arteriole in the kidney?
Larger arteries that split a bunch of times before getting to arteriole
The name for the blood vessel sitting in front of glomerular capillaries in the kidney:
Afferent arteriole
Why is the afferent arteriole important?
Determines the pressure in the glomerular capillaries
How do we find the blood pressure in the glomerular capillaries?
Amount of resistance between renal artery and glomerular capillaries
What is the average BP in glomerular capillaries?
60mmHg
What causes the decrease from 100mmH in the renal artery to 60mmHg in the glomerular capillaries?
resistance in afferent arteriole getting from renal artery to glomerulus
What is the function of the glomerular capillaries?
Area for filtration
first capillary set in a series of 2 capillary beds in the kidney
How many capillary beds are there in the kidney?
2
What is the first capillary bed encountered in the kidney?
Glomerular capillaries
What defines how much filtration occurs in the glomerular capillaries?
Pressure in the glomerular capillaries
What is GFR?
Rate of fluid moving from glomerular filtration bed into a compartment for processing everything that has been filtered
What happens if glucose makes it into filtration?
Body doesnt want to lose glucose so if working normally it should reabsorb it
What is reabsorbed from the filtrate and what happens to the rest that is not reabsorbed?
Body reabsorbs things it needs to keep
other things can pass through and leave body in the urine
What does a high GFR mean?
The higher the processing the better the organ
What allows for alot of filtration at the glomerulus?
High pressure of 60mmHg (x2 the pressure in vascular capillary)
What is the total filtration rate of all glomerular capillaries in the body?
125mL/min
What are things that arent filtered by the kidney (unless something is wrong)?
RBCs
Large proteins
What could cause large compounds to be filtered by the kidneys?
If the glomerular capillaries are not intact d/t life time of poorly controlled diabetes or hypertension
What is manipulated in the kidney by the body to maintain normal levels of blood flow and filtration?
Afferent arteriole
How does the kidney respond if it senses blood flow is too low?
Afferent arteriole relaxes to increase perfusion
How does the kidney respond if renal blood flow is too high?
Afferent arteriole constricts to limit over perfusion
How is autoregulation in the kidney different different than other areas in the body?
The kidney does not have a flat line within the normal limits of autoregulation
slanted line
Why is the slanted line in kidney autoregulation significant?
Helps maintain long term blood pressure control–slant allows for kidney to get rid of fluid when BP is high and retain fluid when BP is low
What is plasma oncotic pressure in afferent arteriole?
28mmHg
What is plasma oncotic pressure trend in the glomerular capillaries?
30mmHg at arteriole end
32mmHg in the middle
36mmHg at the end
What does glomerular plasma oncotic pressure trend up the further along you go?
More fluid is being filtered so the proteins are becoming more concentrated
Where is fluid filtered into from the glomerulus?
Tubule (bowmans capsule)
What does P(tubule) stand for?
hydrostatic pressure in the tubule
What is the value of P(tubule)?
18mmHg
What is the plasma oncotic pressure in the tubule?
0mmHg
proteins should not be filtered if healthy
Where are the proteins that are necessary for the cells in the tubule located?
Tethered to the tubule–dont have any osmotic pressure associated with them
How is NFP calculated in the tubule?
-start with glomerular capillaries
-oncotic pressure in the capillaries
-presssure in the tubule
60-32-18= 10mmHg
What is the NFP in the tubule?
10mmHg
What is the NFP in the tubule so high?
It drives filtration at 125mL/hr
What is normal glomerular filtration rate?
125mL/hr
What is the purpose of the filtration coefficient? (Kf)
Helps to figure out what the filtration rate is
What is the equation for filtration rate?
Filtration rate= NFP x Kf
What is the second arteriole in the kidney behind glomerulus?
efferent arteriole
What does the kidney use efferent tone/regulation for?
Finetune GFR
What makes the efferent arteriole the highest vascular resistance vessel in the kidney?
Large decrease in BP from 60mmHg in the glomerulus to 18mmHg at the end of efferent arteriole
compared to afferent (40 point difference)
What happens as a result if the efferent arteriole is constricting?
upstream pressure is increased which means higher pressure in glomerulus and more filtration
What happens as a result if the efferent arteriole is dilating?
Easier for blood to flow downstream so glomerular capillary blood flow is reduced and filtration is reduced
What does the body do in response to low GFR?
constricts efferent arteriole to drive GFR up
What does the body do in response to high GFR?
Efferent arteriole relaxes to decrease GFR
What vessel has the greatest vascular resistance of any segement of blood vessel in the kidney?
efferent arteriole
Where does most of the blood that moves through the kidneys end up?
Stays in the Cv system and passes into efferent arteriole
What is the second set of capillaries in the kidney?
Peritubular Capillaries
What is the primary action happening at the peritubular capillaries?
Reabsorption
What processes are used for reabsorption from the tubule to the peritubular capillaries?
Pumping systems aor channels where fluid is sent in the tubule and then can be selectively decided what to reabsorb
What percent of filtrate is reabsorbed?
99%
What percent of filtrate is excreted in the urine?
1-2%
What is the route for absorption from the tubule to the peritubular capillaries?
Through or between the cells that line the walls of the tubule
What type of particles fir between the cells?
Wide gaps in the cells in the tubule
water and small things can take that route to be reabsorbed
What is the net filtration pressure in the peritubular capillaries compared to the glomerular capillaries?
NFP is lower in peritubular capillaries
net reabsorption pressure is high in the peritubular capillaries
What is the plasma oncotic pressure in the middle of the peritubular capillaries?
32mmHg (same as glomerular capillaries)
What is the trend for plasma oncotic pressure in the peritubular capillaries?
Reabsorbing more fluid so protein concentration is more dilute as you travel down the peritubular capillary
What is the BP in the peritubular capillaries?
13mmHg
What is BP at the beginning of the peritubular capillaries?
18mmHg (end of efferent arteriole)
How does the kidney use the 2 capillaries to manage equilibirum?
Equal forces of reabsorption in the peritubular capillaries as there are filtration forces in the glomerular capillaries
Where is the reabsorbed fluid emptied back into CV system?
reabsorption ends at the end of the peritubular capillary and empties content into renal vein
What goes through the renal vein?
The blood flowing through the kidney plus everything the kidney reabsorbed
Where is the renal interstitium located?
outside the tubule
What is the renal interstitium made of?
Protein matrix tha contains ions, electrolytes, and larger energy compounds
What does the renal interstitium separate?
Intermediate space between tubule and blood vessels
Everything reabsorbed must pass through the _________ at some point.
Renal interstitium
What is the ISF protein osmotic pressure in the kidney?
15mmHg
What is the pressure in the renal interstitium? (Pisf)
6mmHg
What is the role of pressure in the renal interstitum?
Plays a role in how much fluid is reabsorbed from the filtrate
What is the net filtration pressure in the renal interstitium?
-10mmHG
same as +10mmHg Net reabsorption pressure
What is the process of excretion?
removing waste products from the body via urine
How much is filtered in the kidney?
filtration rate: 125mL/min
RBF: 1100mL/min
a little over 10% of the blood that moves through the kidney is filtered
Are RBCs filtered through the kidney?
No
What portion of the plasma that moves through the kidney is filtered?
1/5
What happens to excretion with increased filtration?
Increases excretion
Where does the end of the tubule empty into?
Ureters then into bladder
What is the equation to calculate excretion?
filtration- reabsorption + secretion
How can excretion be represented and with what units?
Volume or quantities of specific substances being dissolved in the fluid that is being filtered
mL of fluid, mol or mg or a compound
What is secretion?
ability of the bodyd to pump things into the tubule
What is used to pump items back into the tubule?
special transporters
What is the path for items that are being secreted?
Movement from peritubular capillaries into renal interstitium and back into the tubule through the cells
Are special transporters for secretion only for large molecules?
No. Secretion can be used of large or small molecules
How does the kidney get rid of excess potassium?
physically pumps potassium from blood into the tubule to remove it from the body
What part of the kidney decides whether to secrete or excrete?
Processing is dependent on what the tubule cells want to do
What does secretion of specific items depend on?
Location of tubule, hormones in the body that influence the secretion
What usually causes the kidney to filter more fluid at the glomerular capillaries?
Constriction of the efferent arteriole
makes it harder for blood to flow from glomerulus to efferent arteriole and forces more blood to be filtered
What happens to glomerular colloid osmotic pressure when the kidney is filtering more fluid?
colloids would be more concentration when more fluid is filtered
What causes the kidney to filter less fluid?
relaxation of efferent arteriole
What happens to glomerular colloid osmotic pressure if the kidney is filtering less fluid?
proteins arent as concentrated as normal
What happens to filtration fraction with increased glomerular filtration?
increased filtration fraction
What happens to filtration fraction with decreased glomerular filtration?
decreased filtration fraction
What is filtration fraction?
how much fluid is filtered and how much plasma has made it through the kidney
What is a normal filtration fraction?
20%
How is filtration fraction calculated?
FF= GFR/ Renal plasma flow
What is renal plasma flow?
660 mL/min
What is normal renal blood flow?
110mL/min
If hct is .4 what portion of the blood is plasma vs RBC?
40% of 1100 = RBC volume
60% of 1100= plasma volume
How is renal plasma flow calculated?
0.6 x 1100= 660mL/min
What is a normal filtration fraction?
0.19
Where do changes in renal vascular resistance occur?
Either occur at afferent arteriole or efferent arteriole or both
What is the site for renal autoregulation?
Afferent arteriole
(by default also autoregulates GFR)
Where is the site for GFR fine tuning?
Efferent arteriole
What is expected if resistance is increased at afferent arteriole (constriction)?
downstream of high resistance, pressure will be lower
glomerular capillary BP in lower
decreased GFR and decreased renal blood flow
What happens if efferent arteriole is constricted?
occluding outflow from glomerular capillaries
pressure upstream increases
increased pressure in glomerular capillaries–increases GFR but reduces renal blood flow
What happens to renal blood flow with constriction of efferent or afferent arteriole?
Decreased renal blood flow
What happens when afferent arteriole relaxes?
increases glomerular capillary pressure
increases GFR
increases renal blood flow
What happens when efferent arteriole is relaxed?
decreased glomerular capillary pressure
decreased GFR
increase renal blood flow
What happens to renal blood flow when either the afferent or efferent arterioles are dilated?
Renal blood flow increases
What pressure does the kidney autoregulation function at?
50-150mmHg
GFR starts to drop off at pressure above 50mmHg
Why is autoregulation in the kidney compromised with a sick/unhealthy person?
when sick, blood vessels have a hard time dilating
What is renal autoregulation dependent on?
Ability of afferent arteriole to dilate
Why does someone with chronic HTN or uncontrolled DM likely have poor renal autoregulation?
Blood vessels (including afferent arteriole) do not relax normally
What is the lower limit for renal autoregulation in a sick person?
50mmHg is ok for healthy person but a sick person probably needs a higher BP for kidneys to be happy
Is renal blood flow is autoregulated, what is also regulated by default?
GFR: constant amount of blood going through the kidneys should provide relatively constant GFR
What does it mean that autoregulation on a graph remains pretty flat even at pressures higher than 150mmHg?
The kidney is good at autoregulating GFR at high pressures
Why is it important to have good GFR autoregulation at high pressures?
Prevents massive amounts of fluid output via urine
How would it be problematic if GFR wasnt well regulated at high pressures?
If someone had area of ischemia the body is trying to perfuse by increasing BP–the kidney wouldnt allow it because it would just dump that extra fluid out into the urine
What happens to GFR autoregulation at low pressures?
GFR is not as well autregulated compared to renal blood flow at low pressures
GFR starts to drop off well above 50mmHg
What is urine output correlated with?
renal blood flow and GFR autoregulation
What is normal urine output for healthy person?
1mL/min
What happens to UOP with increased BP?
increased UOP
What happens to UOP with decreased BP?
decreased UOP
Why does GFR drop with low BP (ex: 60mmHg)?
reducing GFR reduces urine output to conserve volume and increase BP
renal blood flow is still regulated
Does renal autoregulation rely on RAAS?
no, it is independent
What can the tubule do to help if renal filtration isnt doing enough?
tubular secretion can help–cells in tubule grab things to pump into tubule
What type of filtration patter does sodium follow?
Filtration and partial reabsorption
What filtration pattern does glucose follow?
Filtration and complete reabsorption
Where is filtered glucose reabsorbed?
proximal tubule
What is indicated if there is glucose in the urine?
There should not be glucose in the urine
Pt either has high blood sugar where its not getting reabsorbed or there is something wrong with transport system used to reabsorb
How does filtration with heavy secretion work?
only a small amount was filtered, the rest travels past efferent arteriole then is actively secreted via a transport system that moves all of the compound into the renal tubule for excretion
What is an example of a compound that goes through filtration with heavy secretion?
Para amino kippuric acid (PAH)
What is Para amino kippuric acid?
Diagnostic compound used to estimate renal blood flow
removal is dependent on blood moving through the kidney
How can you tell renal blood flow from PAH levels removed from circulation?
Lower amounts of PAH being removed from circulation = lower renal blood flow
higher amounts being removed from circulation= higher renal blood flow
How much filtrate is reabsorbed based on GFR?
124mL/min
Why is there no protein osmotic pressure in the tubule?
There should not be any proteins in the tubule
What is the inner layer of the glomerular capillaries composed of?
inner layer made of endothelial cells
What makes the glomerular capillaries more permeable that systemic capillaries?
Fenestrations
What are fenestrations in the glomerular capillaries?
specialized opening in renal glomerular endothelium
What are the 3 layers of glomerular capillaries?
Inner layer: endothelial cells
Basement membrane (middle): big piece of connective tissue
Outer layer: Epithelium
What is the epithelial layer of glomerular capillaries designed for?
back end of the capillary–a layer of epithelial cells specialized to provide support and structure to capillary bed
Why is support needed by the epithelial layer for the glomerular capillaries?
Support is needed because pressure is really high in these capillary beds
What makes up the epithelial layer?
Podocytes
What are podocytes?
similar function as astrocytes in the brain
they help support glomerular capillaries in the kidney
How does fluid still get through podocytes?
Podocytes have foot processes and slit pores–allows fluid to still pass through
What is found in the area around the epithelium and basement membrane to control what gets into the glomerulus?
A bunch of different negative charges–used to help repel things also have a negative charge from getting into fenestrations
What type of molecules are repelled by the negative charge of epithelium and basement membrane?
anything with a negative charge
proteins in the blood are negatively charged so they are repelled and prevented from being filtered
What do podocytes help with when glomerular pressure is really high?
Help with swelling in glomerular capillaries
help to keep surface area of glomerular capillaries in check
What happens to glomerular capillaries if BP is high for a REALLY long time?
Eventually podocytes cant protect them and the capillaries are blown out and swollen by the high BP and eventually fall apart
What is Dextran?
Big synthetic sugar compound that chemists can modify to make larger or smaller
How does a neutral particle compare to a positively charged particle when looking at filterability?
positively charged will be more filterable because it doesnt have negative charge to repel it from getting through fenestrations
What does polyanionic mean?
Multiple negative charges on it
How does neutral dextran filterability compared to polyanionic dextran?
Polyanionic has much lower filterability–its repelled from getting through fenestrations
What happens to filterability as the size of a compound increases?
filterability is reduced
larger compounds arent as likely to sneak through fenestrations
What is inulin used for?
synthetic compound injected into patient out clearnace of inulin
more accurate number for GFR
Why is inulin better predictor of GFR than creatinine?
Creatinine has variability from person to person–doesnt follow same kinetics through kidney as inulin
What are some things discussed in class than can be easily filtered?
-small things (water, sodium)
-glucose
-inulin
Can myoglobin be filtered through the glomerulus?
MW is 17,000
its filterable but less than water and Na (0.75)
we shouldnt have myoglobin floating int he blood so not an issue
What is the filterability of albumin?
Low (0.005)
big molecular weight
What things is the kidney a longer term manager of?
BP
Acid/base balance
Hematocrit
Electrolyte balance
Calcium levels
Long term blood glucose
Drug clearance
Metabolic waste products
Water reabsorption
What is the primary issue if someone has high blood pressure?
Something messed up with the kidneys
How does the kidney function to for longer term acid/base balance?
The kidney manages bicarb levels and can get rid of excess protons
What system decides how much bicarb to reabsorb?
The kidney
How is bicarb filtered?
Small, easily filtered
What happens if we need more bicarb than the kidney is filtering?
The kidney can make its own bicarb
Besides bicarb filtration, how else can the kidney manage pH?
Kidney gets rid of excess protons
What is the short term pH regulator in the body?
Respiratory system
How does the respiratory system manage pH?
Blows off CO2 to reduce proton in the blood temporarily
only short term because lungs expire CO2 but they cant directly expire protons
How does the kidney manage hematocrit?
O2 sensors deep in the kidney–look at O2 levels in the deep medullary portions of the kidney
What happens if the deep medullary portions of the kidney sense a low O2?
The kidney releases erythropoietin
What is the function of erythropoietin?
Increases RBC in circulation by stimulating bone marrow to produce more RBCs–increases ability to transport O2 around and increases oxygenation levels
How does the kidney maintain electrolyte balances?
Everything we eat get absorbed into blood stream–kidney gets rid of excess electrolytes that come in from our food (EX: Na+)
How does the kidney manage calcium levels?
Kidney can pick and choose how much Ca2+ to reabsorb from food
Where is vitamin D activated?
By the kidney
What is one vitamin that would need to be supplemented if they kidneys arent working?
Vitamin D
How does the kidney function to maintain long term glucose levels?
Kidney figures out how much glucose to reabsorb
What happens to glucose absorption if more glucose is being filtered?
The more glucose filtered, the more glucose reabsorbed (up to a point)
What happens to glucose reabsorption if blood sugar is slightly elevated?
They kidney will still reabsorb if there is a slight excess
What happens to glucose reabsorption if blood sugar is 900?
way more glucose than the kidney can reabsorb from filtered fluid–the glucose is lost in the urine
How are the kidneys a safety valve for extremely elevated glucose?
Kidney can reabsorb some of it but then excretes extra glucose in the urine
How does the kidney help with drug clearance?
Gets rid of fewer drugs than the liver–but some drugs are transported out of the blood and into the urine
What process is used by the kidney to get rid of drugs?
Secretion of the drug from the blood stream to the urine
What is the main metabolic waste product the kidney gets rid of?
Nitrogenous compounds
What metabolic waste product is created with severe diabetes?
Causes messed up nitrogen compounds in the blood
What is an example of a nitrogen waste product excreted by the kidneys?
Urea
How does the kidney function as an osmolarity regulator?
Kidney can differentiate salt from water reabsorption–helps to manage blood osmolarity
How does the kidney balance hypernatremia?
Kidney can get rid of salt and still hang on to water–further dilute salt in the blood
What manages the kidneys ability to regulate osmolarity?
Managed by ADH and osmoreceptors in the brain
What is the order of the renal blood vessels starting at renal artery to the afferent arteriole?
Renal artery
Segmental arteries
Interlobar arteries
Arcuate arteries
Interlobular arteries
(Then at afferent arteriole)
What is the order of the renal blood vessels in the nephron?
Afferent arteriole
Glomerular capillaries
Efferent arteriole
Peritubular capillaries
What capillart bed gives rise to the venous system of the kidney?
Peritubular capillaries–converge to giver larger and larger veins
What is the order of the veins in the kidney starting from the peritubular capillary?
Interlobular vein
arcurate veins
interlobar veins
segmental veins
renal vein
How many nephrons do we have at birth?
2 million (1million in each kidney)
What part of the kidney is in charge of reabsorption/secretion into urine to get rid of waste?
Tubular system
At what age do we start losing nephrons?
start to lose a few over the years by age 40
What is the functional unit of the kidney?
the nephron
What components make up the nephron?
Afferent arteriole
Glomerular capillaries
Efferent arteriole
Peritubular capillaries
Tubule system
What are the 2 type of nephrons?
Superficial nephrons
Deep nephrons (inner)
What do the inner nephrons have that the superficial nephrons done?
Vasa recta
What type of nephrons are most of the nephrons in the kidney?
Superficial nephrons (cortical nephrons)
90-95%
Where are the glomerular capillaries located in the superficial nephrons?
in the cortex
Where are the peritubular capillaries and tubule in superficial nephrons?
Dip into the outer medulla
Why is it not an issue delivering O2 and nutrients to cortical nephrons?
They are more superficial so it is easier
What percent of nephrons are deep inner medullary nephrons?
5-10%
Which part of the kidney is the most sensitive to low BP?
inside the deep parts of the kidney
Why are the deep parts of the kidney sensitive to low bp?
They have a limited supply of peritubular capillaries–less reabsorption and less O2 and nutrient delivery
Which part of the kidney is the most sensitive to hypoperfusion?
The deep medullary part of the kidney
Why are the peritubular capillaries limited in the inner medullary nephrons?
fewer peritubular capillaries
peritubular capillaries here have an unequal number of ascending and descending capillaries
What are the peritubular capillaries ascending and descending portions called in the inner nephron?
Vasa recta capillaries
What is the ratio of ascending to descending vasa recta capillaries in the kidney?
One descending blood vessel gives rise to 2 ascending vessels
Why is there a split in the ascending vasa recta vessels?
important to have a split to decreases flow and not wash out the renal interstitium
slows down blood velocity in ascending blood vessel since there are 2 pathways
What happens if ascending vasa recta velocity is too high and why would this be a bad thing?
Increased fluid would wash everything out of the renal interstitium–reabsorption process will be affected
proteins and solutes are all going to be washed out of interstitium and increases urine volume
What does flow in the ascending vasa recta influence?
influences renal interstitum and can affect reabsorption if not a normal fluid flow rate
What happens if ascending vasa recta blood flow velocity is decreased?
This is what we want**
blood moving from medulla to cortex–its encountering less concentrated environment in the renal interstitium where is absorbed a bunch of stuff in the deep renal interstitium
this allows for opportunity for proteins to move back into the renal interstitium with their concentration gradient
Where are the kidney located in the body?
Tucked below the diaphragm
Where are the renal artery and vein located?
Underneath mesenteric artery
What does the mesenteric artery supply?
supplies blood to GI/intestines
What is located on top of each kidney?
Adrenal glands (suprarenal glands)
Where do the ureters empty their waste?
Bladder
What organ contacts the top lateral portion of the right kidney?
Liver (hepatic surface)
an some contact with the colon
What organ comes into contact with the top left kidney?
Stomach (gastric surface)
What contacts the middle part of the left kidney in the body?
Pancreas
What comes into contact with the lower part of the left kidney?
colon
Why is it important to know which organs touch the kidneys?
Important when looking at cancer to see what areas could spread to the kidney (ex: pancreatic cancer)
Why is renal cancer rare?
Kidney do not generate new nephrons very often
If someone does have renal cancer what is usually the cause?
Usually metastatic from other areas near the kidney
What quadrant are the right and left kidney in the abdomen?
right kidney: RUQ
left kidney: LUQ
What structures come together to form the ureter that then empties into the bladder?
Minor and major calyxs
How does the bladder empty?
Through urethra
What happens with kidney stones?
impaired urine flow–blockage in ureter will increase upstream pressure in the kidney causing pain
Where is pain usually when someone has a kidney stone?
Pain is referred to lower back
Where is the prostate gland located in men?
Prostate gland wraps itself around early parts of the urethra
Why is BPH an issue for men as they age?
prostate enlarges and squishes the urethra making it difficult to empty bladder
What is the reason why older people go to the bathroom frequently?
bladder is not completely emptying
Which nervous system influences bladder emptying?
Both sympathetic and parasympathetic influence bladder emptying
What nerve controls bladder/stool emptying?
Pudendal nerve
Where does the pudendal nerve arise from?
Spinal nerve S2, S3, S4
Why is it uncommon to surgically remove the prostate if someone has prostate cancer?
Pudendal nerve runs close to the prostate gland–prostate gland easy to remove but high risk of cutting pudendal nerve
What happens if the pudendal nerve is cut/damanged?
fecal and bladder incontinence
Who is the guy who had prostate cancer for 25 years and what did he take the slow the cancer progression?
Linus Pauling
took vitamin C to slow down cancer
How does vitamin C help with cancer prevention?
No clear study results but antioxidant compounds can play a role in cancer prevention from free radical oxidative stress
Where is the initial place where fluid is filtered from the glomerular capillaries into the proximal tubule?
Renal Corpuscle (bowmans capsule)
What is the first part of the tubule?
Proximal convoluted tubule
What comes after PCT?
proximal Straight tubule
What are the parts of the loop of henle?
Small thin descending structure then hairpin turn then heads up via thin ascending limb that widens to thick ascending limb
Where are the macula densa located?
Thick ascending limb of the loop of henle
What is the function of the macula densa?
place where kidney monitor filtration rate–tells the kidney now much fluid is being filtered by counting Na+ and Cl-
How do the macula densa control efferent and afferent arteriole?
Macula densa come directly into contact with the efferent and afferent arterioles
How do the macula densa function in renal autoregulation?
Count Na+ and Cl- to increase or decrease GFR based on increased or decreases filtration sensed
What are the 2 parts of the collecting duct?
Cortical collecting duct
Medullary collecting duct
Where does the medullary collecting duct empty?
Into papillary duct and eventually empties into ureters and into the urine
What are the 2 sections of the medullary collecting duct?
Outer medullary collecting duct: more superficial
Inner medullary collecting duct: deep in the structure
What is the structure called where the macula densa come into contact the afferent and efferent arteriole?
Juxtaglomerular apparatus
What are the cells called in afferent and efferent arterioles that measure flow?
Juxtaglomerular cells
What happens if the juxtaglomerular cells sense low blood flow?
juxtaglomerular cells release renin at afferent and efferent arterioles
What does the release of renin by juxtaglomerular cells do?
Renin causes increase in angiotensin II levels and constricts efferent arteriole
What happens when the efferent arteriole is constricted?
increases pressure in glomerular capillaries and increases GFR–restored flow to normal in the kidney
What chemical controls juxtaglomerular apparatus?
Angiotensin II
What is renal clearance measuring?
Describes a quantity of plasma that is cleared of a substance per time
What is the normal unit for renal clearance?
mL of fluid/ minute
What happens to renal clearance if the kidney filters a lot but doesnt reabsorb very much?
High renal clearance
What is the renal clearance if the kidney reabsorbs all of the compound and the fluid?
Renal clearance for that compound is low
What is the filtration rate that all 2million nephrons contribute to get to?
125mL/min
How much filtered fluid is typically reabsorbed?
98-99%
reabsorb 124mL/min
What happens to the remaining 1mL/min of fluid that the kidney does not reabsorb?
1mL/min is normal urine output
what does a variable with a dot on top of it indicate?
Dot means per unit time
in the kidney the time is minutes
What does V with a dot over it indicate?
urine volume per minute
What would the filterability be of a compound that is smaller than a protein and positively charged?
Easily filtered
What would be expected of the concentration of the fluid filtered at the beginning of the PCT from a compound that is easily filtered?
Expect fluid should have the same composition as the plasma prior to being filtered
On average, how much of the fluid that is filtered gets reabsorbed at the proximal tubule?
2/3
How much glucose does the proximal tubule reabsorb?
Proximal tubule should reabsorb all of the glucose is normal levels
under normal conditions no glucose should be left at the end of the proximal tubule
what is the renal clearance for glucose under normal conditions?
Renal clearance is 0–all glucose is reabsorbed so no plasma is cleared of glucose
What is a sign that no glucose has been cleared from the plasma?
No glucose in the urine
What is an example of a compound that goes through filtration without reabsorption?
Inulin
What happens to inulin as it moves through the tubule?
124mL of fluid is reabsorbed but no inulin is reabsorbed
all of the compound would go out in the urine
What happens to concentration of inulin at the bowmans capsule and as it travels through the nephron?
Inulin concentration in the bowmans capsule is the same as the pre-filtered plasma concentration
Later parts of the nephron, inulin gets more concentrated bc fluid is being reabsorbed and the compound is not
What does the concentration of Inulin look like at the collecting duct?
Very high–all of compound with only 1mL of fluid to dilute it
What would be the renal clearance of inulin?
124mL/min
What would the concentration of inulin be like at the efferent arteriole?
No change in concentration
What would the concentration be of Inulin at the peritubular capillaries?
Lower concentration because reabsorbing fluid without reabsorbing inulin
How does inulin concentration compare at the renal artery vs the renal vein?
Inulin concentration is lower at the renal vein than the renal artery
How to figure out concentration of a compound that is freely filterable and not reabsorbed at all:
The amount filtered would be equal to however much was in the plasma that was originally filtered
EX: 125mL filtered= 1.25dL of fluid
What does excretion rate measure?
Quantity of stuff in the urine over one minute
What is the formula for renal clearance?
(Urinary flow x Urinary concentration of compound) / plasma concentration
How is excretion rate calculated?
Urinary flow x Urinary concentration of compound
How many mL in 1dL?
100mL/ 100cc
What is renal clearance used for?
Used to estimate GFR
What is the gold standard compound to figure out GFR?
inulin
Why is creatinine not as reliable as inulin?
variables with creatinine because kidneys secrete small amounts of creatinine
usually when using creatinine it is an over estimate of GFR
What is creatinine a byproduct of?
Skeletal muscle metabolism
Why is creatinine variable?
Is a pt is bed-bound skeletal muscle mass will be low and creatinine will be low so it will interfere with GFR estimate
What does it mean if Inulin clearance is reduced?
Kidney function is reduced
What compound is highly secreted by the kidneys?
Para amino kippuric acid (PAH)
What does the kidney do with Para amino kippuric acid?
secretion–pump to put all of the compound from the peritibular capillaries into the tubule lumen
What happens to the plasma concentration of PAH after excretion?
No PAH in the plasma
clear all of plasma of PAH before it gets to the renal vein
What is the clearance rate for PAH?
Really high and equivalents to renal plasma flow
How do we figure out renal blood flow from renal plasma flow and hct?
(renal plasma flow)/ 1-hematocrit
What percent of PAH can the kidneys remove?
90%
How does the kidney autoregulate blood flow if BP is 200mmHg?
constrict afferent arteriole–some of the pressure will still affect glomerular capillaries
How does net filtration pressure change is glomerular capillary pressure increases?
if glomerular capillary pressure goes up by 30mmHg–net filtration pressure will also go up by 30mmHg
go from normal of 10mmHg NFP to 40mmHg NFP
How can GFR be estimated if the glomerular capillary pressure is increased?
New net filtration pressure times the filtration coefficient
40 x 12.5= much higher GFR
What happens to urine volume if glomerular filtration is increased?
can still only reabsorb 124mL/min–greater volume being filtered would mean greater volume in the urine
Why is it important that the kidney has multiple ways to check and regulate GFR?
If unchecked we would dump tons of urine if GFR was increased
What usually prevents drastic increases in GFR?
Afferent arteriole constriction
What happens to filtration if BP drops to 50mmHg?
Lower pressure in glomerular capillaries causing lower GFR and reduced UOP
What does reabsorption depend on?
reabsorption depends on time–the more time in the tubule the more time for things to be reabsorbed
What happens to the kidney is GFR is low?
Kidneys do not function as a good filter
Not enough being filtered = kidney cant selectively choose what to reabsorb
How does the kidney autoregulate with low blood pressure?
Dilates afferent arteriole
When would renal blood vessels have a hard time dilating?
Uncontrolled diabetes or hypertension can lead to blood vessels that are still and calcified that cant relax properly
How does chronic hypertension cause dysfunction of the afferent arteriole?
Afferent arteriole would be constantly constricting with HTN to prevent over perfusion–causes it to stiffen up over time
What would happen if someone with chronic HTN has a drop in BP?
the afferent arteriole wont be able to dilate because they are use to constricting
What happens at the glomerular capillaries with chronic HTN?
-capillary bed gets beat up
-podocytes cant hold the structure
-capillaries are bulging and spread out
-could cause scarring of cap bed
What cells are responsible for monitoring the flow throughout the kidney?
Macula Densa cells
Where does most reasborption occur?
At the proximal tubule
2/3 of water filtered is reabsorption here
Is there reabsorption happening other places in the kidney besides proximal tubule?
Yes, some reabsorption happening all along the tubule at every segment
What happens to creatinine concentration along the tubule?
creatinine is freely filtered nut not reabsorbed
water is still being reabsorbed so the concentration of creatinine is increasing the further along the tubule we go
What do the macula densa look for to adjust filtration rate?
Look at numbers of primarily sodium also chloride
counts how many sodiums go past the sensor per unit time
What happens if the macula densa cells sense more Na+ than normal making its way to distal tubule?
Kidney interprets the increase in NaCl as high GFR
What happens if the macula densa sense reduced amount of NaCl making it to the sensor?
interpreted as a reduction in GFR
juxtaglomerular cells secrete renin–leading to formation of angiotensin 2
increased angiotensin 2 constricts efferent arteriole and increases GFR
What is the rate limiting step in formation of angiotensin II?
Juxtaglomerular cells secrete renin
How does angiotensin II help increase water rentention?
angiotensin II increases the amount of salt absorbed by the proximal tubule
What fraction of Na/Cl is reabsorbed by the PCT?
2/3
What happens at the macula dense if something causes increased sodium absorption at the PCT?
create NaCl deficit at the macula densa
kidney thinks GFR is low and increase angiotensin II when its not needed
increases GFR higher than normal
What is the time frame for increase glomerular capillary pressure before destruction starts to happen?
increased in glomerular capillary pressure for a day or 2 is ok–years is bad because increases wear on these capillaries in the nephron
What drug can be given to help avoid glomerular capillary damage if angiotensin II is being released when its not needed?
ACE inhibitor or ARB (angiotensin II blocking)
What can cause increased sodium reabsorption in proximal tubule?
High blood glucose
Where is the primary place for glucose and amino acid reabsorption?
Proximal tubule
What other ion is involved in glucose reabsorption?
Sodium
How many sodium per glucose are moved?
1 Na+ drags 1 glucose with it in early parts of PCT
What happens with glucose reabsorption in the kidney if glucose is 500?
Kidneys can reabsorb a little more than normal up to a certain point
If there is more glucose in the tubule what is happening with the transporter?
transporter is working faster than normal and reabsorbing sodium at the same fast rate as glucose–increases sodium reabsorption in the proximal tubule
What is the primary MOA in diabetic nephropathy?
-BG is high
-increase in sodium reabsorption in PCT
-less Na+ making it to macula densa
-Think GFR is low so tries to increase GFR cause damage over time to the glomerular capillary beds because GFR isnt low
Besides the increase sodium intake with high blood glucose, how else does uncontrolled diabetes cause issues?
Glucose is sticky and triggers immune system involvement causing destruction of capillary beds
What is the main issue in the kidney when blood sugar is elevated?
Hyperfiltration–if BG is always high kidney is always trying to increase GFR which over time causes destruction of nephrons
remaining nephrons have to pick up the slack–makes them die off sooner
Are amino acids filtered?
Amino acids are small and get filtered easily
What percentage of amino acids are reabsorbed?
Kidney usually reabsorbs all amino acids that are filtered
How does the body reabsorb amino acids
sodium amino acids co transport–1 Na+ with 1 amino acid
Where do amino acids get absorbed?
Proximal tubule
What happens with a high amount of amino acids in the blood?
More amino acids are filtered and more amino acids absorbed which means more sodium absorbed and less sodium making it to macula densa–increase GFR when not needed
hyperfiltration causing damage to glomerular capillaries
What can cause increased amounts on amino acids in the blood?
Excess pre-workout, high amino acids diets (carnivore diet)
Which is more severe disease process that induces hyperfiltration: hyperglycemia or high amino acids?
Diabetic hyperglycemia is worse becayse the hyperfiltration is all the time when you BG is high even at night.
increased amino acids have to come from your diet so they can at least have a break when you are sleeping
What happens if glucose gets through the PCT without being reabsorbed?
It will not be reabsorbed anywhere else in the tubule
Where is the apical side of the tubule cell?
The side of the cell that makes up the tubule lumen
Where is the basolateral side of the tubule cell?
Cells that make up the walls of the tubule on the side of the interstitium
What are the glucose transporters on the apical side of the cell?
SGLT: sodium glucose transporters
What happens to the SGLT transporters as fluid travels further down the proximal tubule?
Less amounts of glucose–more SGLT 1 transporters later in PCT that have higher affinity for glucose since glucose concentration is reduced
What glucose transporters are on the basolateral side of the tubule?
GLUT transporters
What type of transport happens with the GLUT transporters?
Facilitated diffusion–apical side of the cell is packing glucose into the tubular cell which creates gradient for the GLUT transporter to move glucose to the interstitium for reabsorption
What is SGLT inhibitor used for?
weight loss
How does SGLT inhibition aid in weight loss?
Not reabsorbing as much glucose from the tubule lumen and excreting more in the urine
What is a side effect of SGLT inhibitors?
Increased glucose in the urine creates breading ground for bacteria and the rest of the tubule will have increased sticky glucose stuck to it and could trigger and immune response
What is a potential issue from GLP agonists?
Weight loss from glucagon could be from muscle loss
What are the 3 segments of the proximal tubule?
S1 (early part)
S2 and S3 (later parts)
What segment is the majority of glucose reabsorbed and by what transporter?
S1 segment is where 90% of glucose is reabsorbed
SGLT 2 transporters
What are the charateristics of SGLT 2 transporters?
In S1 segment,
Heavy lifting of glucose reabsorption
1 Na+ for 1 glucose
Low affinity for glucose
High efficiency
What transporters are found in the in the basolateral side of the cell wall?
GLUT 2 transporters: to move glucose from the tubule cell into the interstitium
What glucose transporters are present in S2 and S3?
SGLT 1
What side are SGLT 1 transporters on?
Apical side
How many ions are pumped with SGLT1 transporters?
2 Na+ and 1 glucose
What percent of glucose reabsorption happens at S2 and S3 by SGLT 1 transporters?
10%
How are SGLT 1 transporters able to catch glucose in a low concentration environment?
High affinity pump for glucose, lower capacity
Where are the majority of SGLT 1 transporters located?
S2
Very few SGLT 1 transporters in S3
What determines the amount of glucose being filtered in the kidney?
The plasma concentration of glucose
What is glucose filtered load?
How much stuff (glucose) that is dissolved in the plasma that is being filtered
How do we determine filtered load?
Concentration x flow
If blood sugar is normal (100mg/dL) what would be the normal filtered load of glucose?
100mg/dL x 125mL/min (flow)= 125mg/min
125mL/min = 1.25dL/min
What does the glucose threshold indicate?
The point when glucose starts to show up in the urine (small amount)
What number/range was given in lecture for the glucose threshold?
well above 100 but lower than 200 glucose will probably start showing up in the urine
What happens initially when the urine starts to spill glucose from a graphing perspective?
Small increase in glucose excretion followed by a linear 1:1 relationship where all the excess glucose is showing up in the urine
Why does it take a minute to get to transport threshold?
SGLT 1 transporters start to miss some of the glucose, doesnt mean that all the transporters are maxed out at that point
What is transport maximum?
At some point there is so much glucose in the tubular fluid that the SGLT transporters are maxed out and cant change conformation quick enough
What blood glucose level would be close to transport maximum?
300mg/dL when the ratio becomes 1:1
further glucose filtered at this level will show up in the urine
What cells secrete renin?
Juxtaglomerular cells
What is the rate limiting step in the formation of angiotensin II?
release of renin
What are the juxtaglomerular cells in contact with?
macula densa and the afferent and efferent arterioles
When do the juxtaglomerular release renin?
when the macula densa think GFR is low
what is the process of converting renin to angiotensin II?
renin–> angiotensinogen (produced in the liver) –> angiotensin I –> angiotensin II by ACE
Where is angiotensin converting enzyme found?
in the lungs
What is the primary effect of angiotensin II?
Constriction of the efferent arteriole
What is the primary effect of CCB, beta blockers, and NO donors?
Dilation of afferent arteriole
Which arteriole in the kidney do most drugs effect?
Most drugs effect the afferent arteriole over the efferent arteriole
What do NO donors do to the efferent arteriole?
relax–they relax the afferent arteriole more
What could possibly happen if the afferent and efferent relax equally?
there may not be any effect on GFR because they are counteracting eachother
Where do pressors work?
technically they constrict both the afferent and efferent arterioles–but constrict the afferent more
What is the secondary effect of angiotensin II on the arterioles?
Dilate the afferent arteriole via nitric oxide release–increase pressure in the glomerulus and increase GFR
prevents further reduction in renal blood flow
How does angiotensin II help with water conservation?
increases NaCl and water reabsorption at the PCT–reabsorb more fluid being filtered so we lose less and can expand blood volume and increase BP
What are the receptors for Angiotensin II called and where are they located?
AT1 receptors–all throughout the body
What is the main effect of angiotensin II binding to AT1 receptors in the kidney?
Increases Na/K ATPase pumps in the proximal tubule
Speeds up transporters that are dependent on that pump for their sodium gradient (secondary active transporters)
What happens to ion concentrations when the Na/K ATPase pump is increased?
Drops Na+ concentration inside the cell increase likelihood of Na+ coming across the cell through one of the exchangers
Which secondary transporter is primarily effected by angiotensin II?
NHE in the proximal tubule
How is NHE effected by angiotensin II in the kidney?
speeds up the reabsorption process of bicarb
How does bicarb get into the renal interstitium?
through Na/HCO3 transporter
What type of transporter is the Na/HCO3- transporter?
symporter/ secondary active transport
How does the Na/HCO3- transporter pump ions?
pulls sodium and bicarb out of the cell
What drives the Na/HCO3- pump?
Intracellular bicarb drives this pump
What are the 2 pathways for tubular reabsorption?
Paracellular pathways
Transcellular processes
What type of transport happens through the paracellular pathway?
Passive diffusion
What are the junctions between the tubule cells of the kidney like?
They are called tight junction, but some parts of the kidney have tighter spaces than others
What are the junctions at the PCT like?
Spaces are wide and a lot of things get reabsorbed between the spaces here (paracellular)
What is a common ion that gets dragged between the cells during reabsorption?
Chloride; reabsorption of sodium through transport processes makes the places where its being reabsorbed more positive
What draws chloride into the cell through the paracellular pathway?
It follows the positive charge of sodium–sodium reabsorption pulls chloride along with it
How do ions move when using transcellular processes?
Move through a transporter or channel in the cell wall for reabsorption
What drives trancellular processes?
Active transport driven
Does chloride get reabsorbed through the cells?
No, it typically takes the paracellular route between the cells
What route do aquaporins in the cell wall take for reabsorption?
Transcellular route for water reabsorption in the PCT
What has to happen in order to have movement of water/reabsorption of water?
Have to reabsorb other things to create a gradient for water to move
How does a concentrated renal insterstitium affect water reabsorption
Makes it easier to reabsorb water via osmosis
What items are in the renal interstitium that can make it more concentrated?
Proteins, filaments, urea
What is the benefit of keeping urea in the renal interstitium?
Helps retain water during periods of dehydration
Which parts of the kidney have tight junctions between the cells?
Areas that are impermeable to water–usually lack aquaporins
Where does everything reabsorbed in the PCT end up?
In the renal interstitium then goes to the peritubular capillaries
What is the normal reabsorption pressure in the peritubular capillaries?
10mmHg
What is bulk flow?
Process of reabsorbing lots of stuff d/t capillary forces
Where is the brush border located?
Brush border is on the apical (lumen) side of the proximal tubular cells
What is the function of the brush boarder?
increases surface area of the cells that make up the lining of the tubule x20
Why it is a good thing to have increased surface area on the apical side of the PCT?
allows for lots of space for transporters to be planted (ex: GLUT)
What is the tubular epithelial cells membrane potential throughout the kidney?
-70mV
Why is it helpful to have -70mv membrane potential in the tubule cells of the kidney?
gives a platform the help draw in sodium
electrical and chemical gradient–driving secondary active transport
What is the tubular lumen charge in the PCT?
-3mV
Why is the PCT lumen a negative charge?
Product of ions left over in the tubule
Lots of chloride in the PCT lumen
How does chloride follow sodium?
There is a lag
not very much chloride reabsorbed in the 1st half of PCT
More chloride reabsorbed in the second half of the PCT
Does sodium concentration build up in the PCT?
No because as sodium is being reabsorbed, water is also reabsorbed at the same rate
What type of proteins occasionally get filtered into the PCT?
smaller compounds used for signaling (growth hormones)
peptides
can happen with albumin but not oftem
What are peptides?
Smaller string of amino acids (10-20 amino acids stuck together)
How much protein gets filtered into the PCT each day in a health person?
1.8 grams
How much of the protein that is filtered gets reabsorbed by the proximal tubule?
1.7g
How much protein is in the urine of a healthy person?
100mg–not enough to make the urine cloudy—very low concentration
What process do the PCT endothelial cells use to get rid of the protein fitered?
Endocytosis (pinocytosis)
What is the process of endocytosis at the PCT with proteins?
Proximal tubule cells grab the proteins–pulls them inside the cell to pull apart into amino acids that it can easily reabsorb
Where does pinocytosis occur along the kidney?
Only happens at the PCT–if the proteins make it past PCT there isnt a pathway for the proteins to be reabsorbed
What happens if the proteins make it past the proximal tubule?
They will either get stuck in the brush border or get flushed out
What is the absolute max amount of protein the proximal tubule can reabsorb?
1.7g
What is an example of an issue that causes increased levels of proteins to be filtered
Diabetes and sepsis
What happens when excess proteins get stuck in the renal tubule?
Cause issues in the tubule–potential for the proteins to be washed out with time but very difficult to get them out
What is the kidney dependent on to regulate acid base regulation?
Enzymatic activity of carbonic anhydrase
Which pump is linked to carbonic anhydrase function?
NHE
What is the primary reabsorption process for sodium at the PCT?
NHE: 1 Na+ reabsorbed for every H+ booted out
What increases the chances that bicarb filtered into the tubule lumen will be reabsorbed?
Extra protons in the tubule lumen
How does the proximal tubule regulate bicarb levels in the body?
Through the function of NHE
What does bicarb combine with to from in the proximal tubule?
HCO3- combines with a proton to form carbonic acid
What speeds up carbonic acid to disassociate into CO2 and water?
Carbonic anhydrase
What does anhydrase mean?
To take out water from the acid
How do water and CO2 reabsorb into PCT cell?
Passive diffusion
Where is carbonic anhydrase located?
Wedged in cell wall of PCT tubule and in the lumen side of PCT tethered to the cell wall ALSO in the proximal tubule cell
What happens to CO2 and water after it enters the cell?
Carbonic anhydrase can put them back together into carbonic acid
What does carbonic acid disassociate into in the cell?
Protons and Bicarb
What happens to the protons and bicarb once they are in the cell?
proton used again by the NHE pump to reabsorb more bicarb
Bicarb reabsorbed into interstitium through unknown path (unclear)
What happens if there is no more bicarb in the lumen and H+ is pumped out by the NHE?
H+ usually binds to something else to be secreted–usually ammonia and excreted as ammonium
Why is is good for excess H+ in the lumen to bind to ammonia?
Helps to buffer the urine so there arent just free protons going out in the urine
What is the MOA of carbonic anhydrase inhibitors?
NHE not cycling as fast and bicarb will not be absorbed
What is the net result on pH with carbonic anhydrase inhibitors?
Lose a lot of bicarb–causing acidosis
How do carbonic anhydrase inhibitors work as a weak diruetic?
Less sodium reabsorption since NHE isnt working–more sodium in the urine drawing more water in the urine
How do the cells in the proximal tubule produce their own bicarb?
Glutamine (produced in the liver) is converted by the proximal tubule cell into bicarb and ammonium
What is the chemical formula for ammonium?
NH4+
How much bicarb is made from 1 glutamine?
1 glutamine is turned into 2 molecules of bicarb and 2 molecules of ammonium
What happens with the kidneys ability to make its own bicarb in someone with liver failure?
Liver failure= not producing enough glutamine
People in liver failure have a hard time balancing acid base status
What parts of the kidney form its own bicarb?
Proximal tubule is not the only place that can form new bicarb, but most of it happens at the PCT
What is the function of ammonia?
Urinary buffer to bind to free H+ in the tubule
What is the function of phosphate outside the cell in the tubule?
urinary buffer
sodium phosphate is a good buffer for protons to get them out of the body
How is calcium reabsorbed at the PCT?
Through the paracellular route and transcellular route in the PCT
What transporter allows for transcellular passage of Ca2+?
Calcium selective pump
What motivated calcium to come into the cell through the paracellular route?
Cell is negatively charged and calcium concentration gradient is high in ECF
If something in the kidneys increases reabsorption rate, it typically increases _________ reabsorption rate because it is dragged with everything else.
Calcium
How is the calcium dealt with on the basolateral side of the cell?
Calcium removal system: Calcium ATPase, Na/Ca exchanger both share the workload of getting ride of calcium through transcellular route
Why is calcium filterability at the glomerular capillaries variable?
Can be based on acid/base
Not all the calcium in the plasma is subject to filtration especially if it is handing around something that wont be filtered (albumin)
Where is the parathyroid gland located?
On either side of the thyroid
What is the function of the para thyroid gland?
Monitors level of calcium in the blood (ECF)
What does the parathyroid gland do when calcium levels are too low in the blood?
Released parathyroid hormone (PTH)
What functions does parathyroid hormone have?
1) Encourages vitamin D3 activation for calcium reabsorption from dietary intake
2) influences calcium reabsorption system in the kidney by increasing calcium channels
3) stimulates bone breakdown by osteoclasts (decrease osteoblast activity)
What are the cells that break down bone?
Osteoclasts
What makes up bone?
Calcium and phosphate fused together
What is the function of osteoclasts?
Tear down bone and liberate calcium and phosphate
What is responsible for long term calcium storage in the body?
Bones
What are osteroblasts?
Bone building cells–increase bone density by sticking calcium and phosphate together
What does the root word blast mean vs osteo?
Osteo= bone
Blast= build
What is happening to someones bones if they are chronically hypocalcemic?
Porous bones more likely to fracture
How does the Parathryoid gland respond to high calcium levels?
PTH levels are low–decrease osteoclast and increase osteoblast
How much calcium is reabsorbed at the proximal tubule?
2/3
Safe bet than any compound gets reabsorbed 2/3 at proximal tubule
Where are organic compounds secreted?
Proximal tubule
How do organic cations and anions make it into the tubular cell?
They leak out of the porous peritubular capillaries into the renal interstitium
transporters move compound from renal interstitium into cell
How are organic compounds removed from the cell once they are there?
Organic cations: proton cation antiporter
organic anions: Alpha keto gluterate
How does the proton cation antiporter move the organic cation out of the tubule and into the lumen for excretion?
Moves one proton into the cell from the lumen and moves the cation out to the lumen
Examples of endogenous organic cations:
Ach
choline
creatinine
dopamine
epinephrine
norepi
histamine
serotonin
Examples of exogenous organic cations (drugs):
Isoproterenol
Atropine
Morphine
Procaine
Quinine
Tetraethylammonium
How are organic anions removed from the body?
removed via sodium dependent process with alpha keto gluterate
Where is alpha keto gluterate found?
Compound floating in the cell
What is the process of moving alpha keto gluterate into the cell?
3 sodiums in for each AKG in
How is the organic anion moved from the renal interstitium into the cell?
antiporter with aKG moves the anion into the cell
What allows organic anion to be moved into the tubule lumen once in the cell?
Facilitated transporter
What are examples of endogenous organic anions?
Bile salts
Fatty acids
Hippurates
Prostaglandins
Uric acid
Oxalic acid
What are examples of exogenous organic anions (drugs)?
Furosemide
PCN
Salicylates (ASA)
Sulfonamides
Acetazolamide
Chlorothiazide
What does the kidney do with PCN?
Organic anion–kidney completely removes it from the blood with aKG
When were the systems for organic compound removal discovered?
During WWII
Blood levels of PCN were dropping faster than they wanted–found that is they added synthetic hippurate in patient the same time they took PCN, the abx would stay in the body alot longer
When did the first person take PCN?
1942
Where did PCN initially come from?
Mold–it was difficult to produce at the time so wanted to find a way to prevent PCN levels in the blood from dropping so fast
Why was it discovered beneficial to give patient synthetic hippurates when taking PCN during WWII?
PCN and hippurates use the same transporters for secretion
giving higher concentrations of hippurates competitively inhibits the secretion of PCN
Where does the proximal tubule end?
Straight proximal tubule–then narrows into the loop of henle
Part of the nephron that narrows and dips into the medulla:
Thin descending loop of henle
What happens to renal interstitium the deeper you travel in the nephron?
Deeper in the nephron= more concentrated renal interstitium
What happens to tubular fluid as it moves through descending loop of henle?
As long as this part of the tubule is permeable to water–should have water being reabsorbed as tubular fluid is moving into more concentrated environment
Where does most filtered water reabsorption occur?
Thin descending loop of henle and proximal tubule
Is there ion transport happening at thin descending loop?
No, Not a lot of ion transporters here
Is the thin ascending limb permeable to water?
Relatively impermeable to water
What is the environment like as the fluid travels up the thin ascending loop?
More dilute environment as the fluid moves up
What is the transport system at the thin ascending loop?
Na/Cl ATP transporter
Reabsorbs sodium and chloride in small amounts in the thin ascending limb
What part of the nephron is after the thin ascending limb?
Thin ascending limb widens out to thick ascending limb
Is there water movement at the thick ascending limb?
No relatively impermeable to water
What is the thick ascending limb important for?
Reabsorption of cationic electrolytes from tubular fluid
How is ion transport accomplished in the thick ascending limb of loop of henle?
Lots of space between the cells for ions to be reabsorbed
What percent of ions get reabsorbed at the thick ascending loop?
25% of ion reabsorption occurs here
What are common cationic electrolytes absorbed at the thick ascending limb through the paracellular route?
Mg2+ and Ca2+
What drives Mg2+ and Ca2+ to be reabsorbed via paracellular route?
System that allows K+ to leak into tubular fluid (lumen)
K+ channels on tubule side of the cell–increases K+ in the lumen
K+ leaves into the lumen based off its concentration gradient (high K+ in the tubule)
How does potassium going into the lumen in the thick ascending limb of the loop allow for Mg2+ and Ca2+ reabsorption?
Makes the charge in the inside of the tubule lumen +8mV
+8mV is the force that pushes divalent cations (Mg and Ca) to be reabsorbed via paracellular route
Is there acid base balance in the thick ascending loop?
a little acid base balance happening here–NHE located here
Where is the big pump that moves 4 ions located in the kidney?
Thick ascending limb of the loop of henle
What ions does the big pump at the thick ascending limb move?
1Na+, 1K+, 2Cl- at the same time from the tubule fluid (lumen) into the thick ascending limb of the tubules cells
What happens to some of the K+ that gets pumped into the tubule cell from the transporter?
Some of the K+ pumped in leaks back out into tubule fluid
Why is the reabsorption of ions at the think ascending limb important?
plays an important role of generating concentrated renal interstitium
What happens to renal interstitium as more stuff is reabsorbed into tubular cells?
More stuff in renal interstitium= more concentrated
What is the mechanism of action of loop diurectics?
Shut down NKCC transporter and renal interstitium becomes less concentrated–lose the ability to reabsorb water via osmosis
What is the most powerful diuretic class?
Loop diuretics
What happens with water reabsorption if renal interstitium isnt concentrated?
makes it difficult to reabsorb water into the cell from the tubule lumen
More water end up in the urine increasing UOP
What is the osmolarity of the deepest part in the renal medulla when the kidney is trying to conserve water?
1200
What is the most concentrated a renal insterstitium can be?
1200mOsm
What dictates water permeability at the collecting duct?
ADH
What is urine concentration dependent on?
How concentrated the renal interstitium is
Why can lizards live so long in the desert?
they can make their renal interstitium VERY concentrated 3000mOsm–retain alot of water
What does urine osmolarity correspond with?
Urine osmolarity equal to renal interstitium
What happens to renal interstitium throughout the tubule when a loop diuretic is given?
Less concentrated renal interstitium
all interstitial numbers get really low (250-300 in the medulla)
How does the distal tubule regulate calcium uptake?
Distal tubule is sensitive to parathyroid hormone
What does PTH do to the distal tubule?
increases number of calcium channels at the lumen side of the cell (Na/Ca exchanger and Ca ATPase)
What transporters are at the basolateral side of the distal tubule to get calcium back into the interstitium?
Primary transporter is Na/Ca2+ exchanger (3 sodium in for 1 calcium out)
What happens if juxtaglomerular cells sense an increase in flow?
Reduce renin–reduces angiotensin II–dilates efferent arteriole to decrease GFR
