Kidney and GFR Flashcards
Glomerular Filtrate and Urine
Glomerular filtrate and urine have different composition–> get this through tubular reabsorption and tubular secretion
- filtrate formed in the nephron: glomerular filtrate
Glomerulus
- Glomerular capillaries have an endothelium that is fenestrated
- Podocytes are epithelial cells covering the glomerular capillaries
- Filtration membrane (basement membrane) lies in between the podocytes and the capillary endothelium
- Mesangium is a supporting tissue consisting of mesangial cells and matrix
The Filter Components of Glomerular Filtration
- Three layers that act as a filter
1. Single layer of endothelial cells lining the glomerular capillaries (containing fenestrations): this restricts the passage of blood cells
2. Glomerular basement membrane: lies between the endothelium and the visceral layer of the capsule (NEGATIVELY CHARGED) - main filtration barrier
- negatively charged, repels - charged things (such as proteins!)
3. single layer of the epithelial cells (called podocytes) lining Bowman’s capsule: phagocytose macromolecules and resitricts passage of medium sized proteins
FILTRATE WITHIN THE BOWMANS CAPSULE IS ESSENTIALLY PROTEIN FREE
-contains all the substances present in plasma in approximately the same concentration (freely filtering ions, etc.)
exceptions: some low molecular weight substances that are bound to proteins (e.g. plasma fatty acids, plasma calcium)
Molecular Weight cut off for glomerular capillaries
- Molecular size is the main determinant of whether a substance will be filtered or retained within capillaries
- MW cut-off: 70,000 Da
- freely permeable to molecules: <7000 Da
Charge and Filtration
- cations are more readily filtered than anions for the same molecular radius
- Serum albumin has a radius of about 3.5 nm (69000Da) but its negative charge prevents filtration
- Albumin has a slightly larger shape and is negatively charged, VERY little gets through (as it is a main plasma protein)
- DON’T WANT TO SEE PROTEIN IN URINE
- In many disease processes, the negative charge on the filtration barrier is lost so that proteins are more readily filtered –> Proteinuria
Forces behind Glomerular filtration
- Capillary filtration is determined by opposing forces
- Hydrostatic Pressure difference across the capillary wall favours filtration
- protein concentration across the capillary wall which determines oncotic pressure opposes filtration
- mostly have hydrostatic pressure, but sometimes a bit of pressure going back into blood due to charge of water
GFR
Glomerular Filtration Rate
volume of fluid filtered from glomeruli into Bowman’s space per unit time (oftern per minute)
-SO important to have the kidneys in homeostasis, needs to be tightly controlled
Affected by:
- Hydrostatic BP within glomerular capillaries is the main determinant of GFR
- Actions of mesangial cells (irregular shaped stellate cells lying between the glomerular capillaries: equivalent to vascular smooth muscle)
- Control of renal blood flow
Mesangial Cells
- capable of contraction in response to:
- angiotensin II (ang II): increases mesangial cell contraction
- anitdiuretic hormone (ADH)
- noradrenaline (NA) -sympathetic innervation
- mesangial cell contraction will reduce flow to glomerular capillaries and in turn reduce GFR
- intraglomerular mesangial cells- have some phagocytotic activity
- extraglomerular mesangial cells (Lacis cells): found at vascular pole and are part of the JGA
Renal Blood Flow
- pressure in the renal artery is approximately equal to systemic BP
- most vascular resistance in the kidneys derives from changing the diameter of the arterioles and small arteries (Control flow into the tubules and glomerulus)
- interlobular arteries (smallest)
- afferent arterioles
- efferent arterioles
-
resistance controlled by
i) sympathetic nervous system
ii) hormones
iii) local mechanisms (e.g. autoregulation)
Renal Blood Flow (Q) = Afferent- Efferent arteriolar pressure (delta P)/Resistance (R)
Controlling resistance is really key to how much blood flow you are getting
Hormones causing vasocontriction and changes in GFR
- angiotensin II
- noradrenaline
- adrenaline
- Depends on how you want to affect GFR
- Large amount of vasoconstricters and constrict efferent and afferent, send BP back to central system
Renin angiotensin system (RAS)
- Ang II preferentially constricts efferent arterioles
- Really on efferent in terms of GFR
- low concentrations of Ang II cause constriction of the efferent arteriole maintaining glomerular hydrostatic pressure and GFR when renal perfusion pressure falls below normal
- High concentrations of ang II cause constriction of both efferent and afferent arterioles
Vasodilators of Efferent and Afferent arterioles
- hormones that cause vasodilation (thus increase renal blood flow and GFR)
1. Prostaglandins (PG’s):
2. PGE2
3. prostacyclin (PGI2) - work on the afferent in particular
- Ang II stimulates the synthesis of renal PG’s, PGE2 and PGI2
- This local production of PG’s counteracts the vasoconstrictive effect of ang II
- Example of negative feedback to fine tune the response
Autoregulatory Hormones of the Kidney
- Prostaglandins
- Resin
- Regulation is completely intrinsic
- -different to others as it is INTRINSIC to the kidneys, doesn’t rely on other regulation from NS
- Autoregulation is virtually absent below 70mmHg (normally operates between 80-180 mmHg) - ** IMPORTANT TO KNOW- if you drop below this, autoregulation will not occur properly
Myogenic Hypothesis
(autoregulation theory)
- When arterial pressure increases the renal afferent arteriole is stretched
- Pressure stretches it, and causes response from stretch sensors and causes constriction to return flow to normal
- Vascular smooth muscle responds by contracting and thus increasing resistance (increase of vascular tone)
Tubuloglomerular feedback
(autoregulation theory)
- Alteration of tubular flow (or a factor in the filtrate) is sensed by the macula densa of JGA and produces a local signal that alters GFR
- Increase GFR, increase filtration coming through –> sensed by macula densa in vascular pole (prostaglandins are then produced locally)
Clearance
- volume of plasma from which a substance is completely removed by the kidney in a given amount of time (usually a minute)
- clearnace for urea in humans is 65ml/min
- that means that the kidney removes all of the urea from 65ml of plasma in one minute