l27 - gastro

renal corpuscle?

The renal corpuscle is the part of the nephron where blood filtration first occurs

It consists of two main structures:

• Glomerulus: A bundle of tiny blood vessels (capillaries) where blood is filtered.

• Bowman's capsule: A cup-shaped structure surrounding the glomerulus that collects the filtered fluid.

how does the glomerulus work to filter blood?

• Blood enters the glomerulus through the afferent arteriole.

• Blood pressure pushes water and small dissolved substances out of the glomerular capillaries.

• These substances enter Bowman's capsule and become filtrate.

• Blood cells and most proteins remain in the blood, which leaves through the efferent arteriole.

how does the filtration barrier of the glomerulus and bowmans capsule work?

There are three layers that substances must pass through:

1. Fenestrated endothelium: Contains tiny openings that allow fluid and small substances through but prevent blood cells from passing.

2. Basement membrane: Acts as another filter, restricting larger molecules, particularly proteins.

3. Podocytes: Specialised cells with narrow filtration slits that provide a final filtration barrier

• this part is part of the bowmans capsule, not the glomerulus

what size solutes can be filtered through the renal corpuscle?

anything under 10,000 molecular weights - MW

what is the fenestrated capillary endothelium permeable to?

freely permeable to water, ions, small solutes - but NOT cells

how does the basement membrane of the renal corpuscle act as a filtration barrier?

the basement membrane is a matrix of negatively charged proteins

• so the basement membrane acts as a CHARGED based filtration barrier to proteins

• so the basement membrane REPELS proteins

how do podocytes of the renal corpuscle act as a filtration barrier?

podocytes are specialised epithelial cells

• the GAPS between the foot processes are what form the filtration barrier

• so podocytes prevent the filtration of PROTEINS and LARGE MACROMOLECULES

explain this photo

this is showing the flow of blood through the glomerular capillaries

• can see we have these forces that act on the capillaries once they reach the bowmans capsule

• these forces either drive filtration or absorption

• but pressure forces fluid into the bowmans space - and one in the bowmans space, we refer to it as FILTRATE

what pressures contribute to net glomerular filtration?

so how much filtration will happen in the glomerular is determined by THREE pressures

HYDROSTATIC PRESSURES

1. glomerular capillary pressure - Pgc

• this is the DOMINANT pressure

• this PROMOTES filtration

• blood enters the glomerulus under very high pressure - this very high pressure pushes filtrate OUT of the blood and INTO the bowmans space

2. Bowmans space pressure - Pbs

• this opposes filtration

• this is pressure in the bowmans space which pushes back against fluid trying to enter it

OSMOTIC PRESSURES

3. glomerular capillary protein plasma pressure - πgc

• opposes filtration

• the blood contains plasma proteins called ALBUMIN - and these are much too large to be filtered through the glomerulus

• SO, these remain in the capillaries, which creates an osmotic force, making water want to stay

how do we regulate glomerular capillary pressure?

glomerular capillary pressure is the dominant pressure which PROMOTES filtration

• it is regulated by altering RENAL BLOOD PRESSURE

How do we calculate net glomerular filtration pressure?

how do we regulate, bowmans space pressure, AND, glomerular capillary protein plasma pressure

we normally don’t as they should remain fairly constant in healthy people!

• so it is primarily only glomerular capillary hydrostatic pressure which is regulated and changes

so why would the kidneys WANT to regulate glomerular capillary hydrostatic pressure - Pgc?

because changing Pgc changes glomerular filtration rate

• so the kidneys can increase the amount of fluid being filtered from the blood

how do the kidneys change the Pgc?

by changing the diamter of the affarent and efferent arterioles

how does HIGHER Pgc affect GFR?

higher Pgc = more fluid pushed into the bowmans capsule = INCREASE GFR

so how do we get higher Pgc?

1. so they constrict the efferent arteriole to increase the resistance of the blood leaving

2. dilate the affarent arterioles to reduce the resistance of the blood coming in

this increases the pressure in the capillary bed > so increases Pgc > so therefore increases the rate of filtration

how does LOWER Pgc affect GFR?

lower Pgc = less fluid pushed into the bowmans capsule = DECREASED GFR

So how do we get lower GFR?

1. we constrict the affarent arterioles so that we restrict the amount of blood coming in, and therefore have less pressure

2. and also dilate the efferent arterioles to reduce the resistance of the blood leaving, and have more reduced pressure

this reduces the pressure in the capillary bed > so reduces Pgc > so therefore reduces the rate of filtration

so how do our kidneys know if they need to increase or decrease GFR?

the MACULA DENSA

what is the macula densa?

specialised cells within the juxtaglomerulas apparatus - JGA

• so found in the distal tubule

• the distal tubule loops back AROUND and THROUGH the glomerulus, allowing the macula densa to communicate with it

how does the macula densa work?

the macula densa works as a CHEMOSENSOR

• so it detects changes in the amount of sodium and chloride in the filtrate

• so if there is change in NaCl, the macula densa is going to sense it

explain what the macula densa does if it detects HIGH NaCl

if the macula densa is being delivered filtrate with HIGH concentration of NaCl, then this suggests filtration is TOO high - so that we need to reduce GFR

1. affarent arterioles will constrict

2. efferent arterioles will dilate

explain what the macula densa does if it detects LOW NaCl

if the macula densa is being delivered with LOW concentration of NaCl, then this suggests that filtration is TOO LOW - so that we need to increase GFR

1. affarent arterioles will dilate

2. efferent arterioles will constrict

and the macula densa can stimulate the release of renin to further help restore the GFR s

so name the 3 things that the macula densa actually regulates

so the macula densa initiates signaling pathways to regulate…

1. renal blood flow = how much blood is flowing through the kidneys

2. glomerular filtration rate = how much fluid actually gets filtered by the glomerulus

3. renin release = helps to activate RAAS in order to regulate pressure and volume

whats the actual definition for glomerular filtration rate - GFR?

it is the volume of plasma that is filtered per unit of time

• so aka the amount of filtrate produced per unit of time

whats the NORMAL glomerular filtration rate?

125 mL per minute

AKA 180L per day!!!

what is glomerular filtration rate a good indicator of?

renal function!

what is renal clearance?

the volume of plasma that is cleared OF A SUBSTANCE by the kidneys per unit of time

• so renal clearance is effectively the volume of plasma that the kidneys effectively completely clear of a particular substance per minute.

what is renal clearance good for?

asessing and monitoring kidney function, understanding the excretion of drugs and toxins, AND studying renal blood flow and glomerular filtration rate

so what does GFR vs renal clearance measure?

GFR measures filtration > should be 125ml/min in a healthy adult

and renal clearance measures removal of a substance > depends on the drug you are measuring

what can we use renal clearance to do?

estimate GFR!

How can renal clearance be used to estimate GFR?

If a substance is filtered by the kidneys but NOT reabsorbed or secreted, then everything that gets filtered ends up in the urine.

This means its renal clearance = GFR, because the amount removed from the blood is exactly the amount filtered.

What three things do we need to know to calculate renal clearance?

We need to know:

1. Urine concentration: How much of the substance is in the urine.

2. Plasma concentration: How much of the substance is in the blood plasma.

3. Urine flow rate: How much urine the kidneys produce per minute.

so how do we calculate renal clearance?

so renal clearance describes the rate at whic substance C is cleared from our plasma by our kidneys per unit of time

SO - if we want to use a substance to measure GFR/renal clearnace, what criteria must this substance mean?

1. it must NOT be reabsorbed from the tubule

2. it must NOT be secreted into the tubule

3. it must NOT be metabolised by the body

so it has to just be FILTRATED into the glomerulus, and then move straight out and be excreted

name 2 substances which meet the criteria required to use them to measure GFR/renal clearance

1. creatinine

• this is a waste product produced normally by the muscls > so the body does NOT metabolise it

• so we commonly use this as a measure

2. inulin

• this is a polysaccharide that is NOT metabolisd by the body

• this is NOT found in the body, like creatinine, it MUST be injected

so what is creatinine useful for

measuring the daily clearance of creatinine is useful for estimating someones glomerular filtration rate

how would we calculate daily clearance rate/glomerular filtration rate

clearance of drug = [concentration of drug urine] x volume of urine excreted per unit of time/[drug in plasma]

= e.g. if you worked out your equation in hours, then e.g. 12.5 liters per hour > but then we need to work it out FOR THE WHOLE DAY

• so need to multiply that by 24!

• 12.5×24 =300

• so read the question carefully so you KNOW exactly what it is asking for!

also remember that a normal GFR is 180L a day - because its 125mls per minute

so if we are trying to assess kidney function - what does it mean if plasma creatinine is low?

this means the kidneys are functioning WELL - clearing about 125mls per minute

• GFR = 125 mls per minute

what happens to our kidney function and plasma creatinine if we lose one kidney?

our kidneys have a LOT of redundancy

• so even though if we lose a kidney, our creatinine/renal clearance drops down to 60mls per minute, our plasma creatinine is still FAIRLY normal, because 60mls per minute is still enough to clear this creatinine

• because again, kidneys have LOTS of redundancy

• GFR = 60mls per minute

when does kidney function become impaired

when GFR drops down to about 25mls per minute

• so VERY LOW

• this means plasma creatinine concentration will increase a LOT as now we cannot succesfully clear it from the body

what is filtered load?

this is the amount of a PARTICULAR substance which moves from the blood, into the bowmans space every minute

how is filtered load different from renal clearance? and give example

• Filtered load = how much of a substance ENTERS the nephron from the blood through filtration.

• Renal clearance = how much plasma is effectively CLEARED of that substance by the kidneys each minute.

1. Filtered load

Imagine your kidneys filter 180 g of glucose per day from your blood into Bowman's space.

That means the filtered load of glucose is 180 g/day.

But that doesn't mean you're peeing out 180 g of glucose!

Normally, almost all of that glucose is reabsorbed back into your blood.

2. Renal clearance

Renal clearance looks at how much of a substance your kidneys actually eliminate in urine, relative to its concentration in the blood.

Because almost all filtered glucose is reabsorbed, virtually none is excreted.

Therefore, under normal conditions, glucose has a renal clearance of approximately 0 mL/min.

so what do we need to calculate the filtered load?

glomerular filtration rate AND the plasma concentration rate of a particular substance

filtered load = GFR x [substance in plasma]

what do we need to make sure we do when calculating things?

make sure we are doing the calculations in ONE unit and one unit only

• so either only mls or only L’s for example

• or only minutes or only hours