Lecture 14: glomerular filtration & renal clearance

Question 1

Describe the structure of the renal corpuscle

Answer 1

• the glomerular capillaries - called the glomerulus
• the glomerulus is the** site of filtration** (where the blood gets filtered)
• the glomerulus is** surrounded by 2 epithelial layers** of bowmans capsule - visceral (inner) & parietal (outer)
• bowmans space is between the visceral and parietal layer which receives the filtrate

Question 2

what is the filtrate that arrives in the bowmans space called?

Answer 2

ultra filtrate or glomerular filtrate

Question 3

What determines the content of the ultrafiltrate?

Answer 3

the glomerular filtration barrier
* it acts as a selective barrier - size of molecules (eg if too large they cant pass through ) and the charge of molecules - the filtration barrier carries a negative charge

Question 4

what are** podocytes**?

Answer 4

• the cells that make up the visceral lining of the bowmans capsule

Question 5

what are the podocytes** primary and secondary processes**?

Answer 5

• podocytes have primary processes which wrap around the glomerular capillaries. these trabeculae in turn have secondary processes called **pedicels **
• the pedicels make the thin gaps called **filtration slits **

Question 6

what does the glomerular filtration barrier consist of?

Answer 6

• the** endothelium of the capillar**y which contain fenestrations that are filled with negatively charged glycoproteins
• the** basement membrane** that the endothelial cells lie on - consists of negatiive glycoproteins & proteoglycans which consist of a negative charge - therefore there is electrostatic repulsion
• **the podocytes and pedicels **(filtration slits) of the visceral epithelium of the glomerulus

Question 7

what is the function of the** capillary endothelium **of the glomerular filtration barrier?

Answer 7

• the capillary endothelium is a barrier to blood cells and platelets, but the glycocalyx within the endothelium has a role in reducing penetration of plasma proteins into the filtrate
• remember the glycoclayx forms charged negative meshwork

Question 8

what is the function of the basement membrane in the glomerular filtration barrier?

Answer 8

• allows passage of molecules depending on their size, shape & charge
• major filtration barrier for proteins - as proteins tend to be large and negatibe

Question 9

what is the function of the pedicels and podocytes of the visceral epithelium in the glomerular filtration barrier?

Answer 9

• the podocytes maintain the basement membrane and can phagocytose macromolecules
• they prevent large blood proteins and blood cells from being filtered moving into the bowmans capsule

Question 10

what is the composition of the ultra filtrate?

Answer 10

• most ions and low MW components that are freely filtered (not hindered/stopped by cell membrane)
• almost total exclusion of plasma proteins eg albumin (due to size and charge)
• exclusion of substances bound to plasma proteins eg Ca2+
• negatively charged macromolecules filtered to a lesser extent and positively charged macromolecules are filtered more

Question 11

what kind of fluid is present in the bowmans space?

Answer 11

An almost protein free ultrafiltrate
* similar composition to plasma except for blood cells and plasma proteins

Question 12

what is meant by the term filtration?

Answer 12

• the bulk flow of** solvent** through a filter, carrying with it those solutes which are small enough to pass through the filter

Question 13

what MW value does the glomerular filtration barrier allow for molecules to be freely diffused?

give examples

Answer 13

it permits free passage molecules with a molecular weight of less than 7000
* eg glucose, amino acids, Na+, K+
* note these molecules are at almost the exact same conc as the conc of them in the afferent arteriole

Question 14

What is the GFR?

Answer 14

• the glomerur filtration rate
• the total amount of filtrate formed by all the renal corpuscles in both kidneys per minute

Question 15

what is the value of the GFR in a healthy individual?

Answer 15

• 125ml/min
• very high rate
• however, most of this gets reabsorbed back into the blood

Question 16

what effect does the presence of a** second resistance vessel (efferent arteriole)** at the end of the glomerular capillary have?

Answer 16

• the presence of a second efferent arteriole indicates that the hydrostatic pressure along the capillary decreases very little
• however, it dosent mean that filtration occurs along the entire length of the capillary
• as filtration occurs, the concentration of non filtered substances eg plasma proteins increases and therefore oncotic pressure increases at the venous end of the capillary

Question 17

what are the forces that govern glomerular filtration?

Answer 17

the starling forces
* hydrostatic pressure of the capillary (pushes fluid out into IF)
* hydrostatic pressure of the IF - pulls fluid in
* oncotic pressure of the capillary (pulls fluid in due to plasma proteins)
* oncotic pressure of IF (pushes fluid out due to IF plasma protein conc)

Question 18

what is Kf in the equation for GFR?

Answer 18

the filtration co - efficient
* it is the product of the glomerular capillary permeability & the area of capillary available for filtration

Question 19

what is the filtered load?

also how is it calculated?

Answer 19

• the total amount of any substance that is freely filtered from the renal glomerular capillaries into bowmans space
• it is calculated by GFR x [X] in plasma

Question 20

what does it mean if the quantity of the substance in urine is less than that of the filtered load?

Answer 20

• tubular reabsorption has occured

Question 21

what does it mean if the quantity of a substance is greater than the filtered load?

Answer 21

• this indicates that tubular secretion must have occured

Question 22

how might the GFR be altered?

Answer 22

• constriction or dilatation of the efferent and afferent arteriole

Question 23

what influence does efferent arteriole constriction vs dilatation have on the GFR?

Answer 23

1. efferent arteriole constriction causes the **hydrostatic pressure of the capillary to increase **which causes an increase in the GFR
2. efferent arteriole dilatation causes the hydrostatic pressure of the capillary to decrease which decreases GFR

Question 24

what influence does afferent arteriole constriction vs dilatation have on the GFR and RBF?

Answer 24

• AA constriction reduces the renal blood flow and also decreases the hydrostatic pressure in the capillary and therefore reduces GFR
• AA dilatation increases renal blood flow as more blood can flow in & therefore increases hydrostatic pressure & GFR

Question 25

why is it important for the kidney to **maintain GFR rate**?

Answer 25

* it is important for the kidneys to maintain a GFR level that is appropiate for the body as the **excretion of H20 and salt is strongly influenced by GFR** * note GFR is also strongly influenced by arterial BP * therefore a rise in BP can cause an increased excretion of H20 and salt - a process called natriuresis * a fall in BP can diminish excretion

Question 26

how do the kidneys regulate their blood flow rate ?

Answer 26

they kidney has **control mechansims** in place that keep RBF ( and therefore GFR) relatively constant as arterial blood pressure increases between 90-180mmhg

Question 27

what are the **2 mechanisms** that the kidney use to control GFR and RBF?

Answer 27

* the myogenic mechanism of the arterioles * tubuloglomerular feedback

Question 28

Describe the myogenic mechanism for renal arterioles

Answer 28

* ie autoregulation * **increased blood pressure** causes the **afferent arteriole to stretch inward ** (this is sensed by the smooth muscle cells in the AA) * the inward stretch **opens stretch activated Na+ and Ca2+ ion channels ** * Ca2+ and Na+ enter the smooth muscle cell which **depolarise **it which causes the **opening of voltage gated Ca2+ channels ** on the SR * this releases intraceullar stored Ca2+ which eventually causes cross bridge formation - ie contraction occurs * when contraction occurs - it creates an **opposing force **to the stretch caused by high BP and therefore it brings membrane back to normal shape

Question 29

How does the **tubuloglomerular feedback** mechanism work for controlling GFR and RBF?

Answer 29

* triggered by an increase in the GFR * an** increase in the GFR** causes **more Na+ to be near the macula densa cells** * there is then **enhanced uptake of NaCl** across the MD cells through the NKCC2 channels which causes an increase in ATP and adenosine * **ATP binds to P2X receptors** & **adenosine binds to adenosine 1 receptors** on the smooth muscle cells of the afferent arteriole * receptor binding results in an** increase of [Ca2+] in the smooth muscle cells ** * increase in [Ca2+] in the smc causes contraction and therefore **constriction of the afferent arteriole** * remember constriction of the AA** causes a reduced GFR**

Question 30

what are examples of **other factors** that can effect GFR and RBF & what effects do they have?

Answer 30

* **sympathetic nerves** - AA and EA are innervated by sympathetic neurons - noradrenaline & adrenaline cause vasoconstriction * **vasoactive factors** - eg angiotensin II (constriction) , endothelin (constriction), NO (dilatation), prostaglandins (dilatation)

Question 31

What is renal clearance?

Answer 31

* the renal clearance of any substance is the** volume of plasma **from which that substance is completely removed ('cleared') by the kidneys per unit time

Question 32

what are the **units** of renal clearance?

Answer 32

**ml/min**

Question 33

what is the **formula** for clearance?

Answer 33

* (urine conc of substance) x (urine volume per unit time)/ plamsa conc of the substance

Question 34

what is the **main function** of the renal clearance formula?

Answer 34

* assessing** renal function in disease**

Question 35

What is inulin used for ?

Answer 35

* it is used to get a very accurate measure of GFR * it is freely filtered, not reabsorbed or secreted and therefore the filtered load equals the mass that is excreted

Question 36

instead of inulin what other substance is used to measure GFR?

Answer 36

* as inulin is not a normal constituent of the body and has to be infused (injected) into the body ... creatinine is used instead * creatinine is a waste product released by muscle and its production is relatively constant

Question 37

what renal processes of the nephron (ie filtration, reabsorption etc) affect creatinine?

Answer 37

* it is freely filtered * not reabsorbed * however a small amount of creatinine is secreted by the proximal tubules

Question 38

how does the value of creatinine compare to the GFR value?

Answer 38

* because some creatinine is secreted in the PCT, the value of creatinine clearance is slightly higher than the GFR

Question 39

what does an increasing plasma [creatinine] indicate ?

Answer 39

a strong indicator of **renal disease**

Question 40

what is PAH?

Answer 40

* one of the organic acids that is secreted by the proximal tubule * freely filtered, not reabsorbed and fully secreted * therefore the excreted amount of PAH equals the amount that entered the kidney via the renal artery

Question 41

What is the **renal threshold** of a substance?

Answer 41

* Renal threshold - **max conc** of substance** in blood **before it first begins to appear in the urine