Lecture 14: glomerular filtration & renal clearance Flashcards
Describe the structure of the renal corpuscle
- 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
what is the filtrate that arrives in the bowmans space called?
ultra filtrate or glomerular filtrate
What determines the content of the ultrafiltrate?
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
what are** podocytes**?
- the cells that make up the visceral lining of the bowmans capsule
what are the podocytes** primary and secondary processes**?
- 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 **
what does the glomerular filtration barrier consist of?
- 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
what is the function of the** capillary endothelium **of the glomerular filtration barrier?
- 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
what is the function of the basement membrane in the glomerular filtration barrier?
- allows passage of molecules depending on their size, shape & charge
- major filtration barrier for proteins - as proteins tend to be large and negatibe
what is the function of the pedicels and podocytes of the visceral epithelium in the glomerular filtration barrier?
- 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
what is the composition of the ultra filtrate?
- 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
what kind of fluid is present in the bowmans space?
An almost protein free ultrafiltrate
* similar composition to plasma except for blood cells and plasma proteins
what is meant by the term filtration?
- the bulk flow of** solvent** through a filter, carrying with it those solutes which are small enough to pass through the filter
what MW value does the glomerular filtration barrier allow for molecules to be freely diffused?
give examples
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
What is the GFR?
- the glomerur filtration rate
- the total amount of filtrate formed by all the renal corpuscles in both kidneys per minute
what is the value of the GFR in a healthy individual?
- 125ml/min
- very high rate
- however, most of this gets reabsorbed back into the blood
what effect does the presence of a** second resistance vessel (efferent arteriole)** at the end of the glomerular capillary have?
- 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
what are the forces that govern glomerular filtration?
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)
what is Kf in the equation for GFR?
the filtration co - efficient
* it is the product of the glomerular capillary permeability & the area of capillary available for filtration
what is the filtered load?
also how is it calculated?
- 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
what does it mean if the quantity of the substance in urine is less than that of the filtered load?
- tubular reabsorption has occured
what does it mean if the quantity of a substance is greater than the filtered load?
- this indicates that tubular secretion must have occured
how might the GFR be altered?
- constriction or dilatation of the efferent and afferent arteriole
what influence does efferent arteriole constriction vs dilatation have on the GFR?
- efferent arteriole constriction causes the **hydrostatic pressure of the capillary to increase **which causes an increase in the GFR
- efferent arteriole dilatation causes the hydrostatic pressure of the capillary to decrease which decreases GFR
what influence does afferent arteriole constriction vs dilatation have on the GFR and RBF?
- 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
why is it important for the kidney to maintain GFR rate?
- 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
how do the kidneys regulate their blood flow rate ?
they kidney has control mechansims in place that keep RBF ( and therefore GFR) relatively constant as arterial blood pressure increases between 90-180mmhg
what are the 2 mechanisms that the kidney use to control GFR and RBF?
- the myogenic mechanism of the arterioles
- tubuloglomerular feedback
Describe the myogenic mechanism for renal arterioles
- 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
How does the tubuloglomerular feedback mechanism work for controlling GFR and RBF?
- 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**
what are examples of other factors that can effect GFR and RBF & what effects do they have?
- 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)
What is renal clearance?
- 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
what are the units of renal clearance?
ml/min
what is the formula for clearance?
- (urine conc of substance) x (urine volume per unit time)/ plamsa conc of the substance
what is the main function of the renal clearance formula?
- assessing** renal function in disease**
What is inulin used for ?
- 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
instead of inulin what other substance is used to measure GFR?
- 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
what renal processes of the nephron (ie filtration, reabsorption etc) affect creatinine?
- it is freely filtered
- not reabsorbed
- however a small amount of creatinine is secreted by the proximal tubules
how does the value of creatinine compare to the GFR value?
- because some creatinine is secreted in the PCT, the value of creatinine clearance is slightly higher than the GFR
what does an increasing plasma [creatinine] indicate ?
a strong indicator of renal disease
what is PAH?
- 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
What is the renal threshold of a substance?
- Renal threshold - max conc of substance** in blood **before it first begins to appear in the urine
