Lecture 4 - Glomerular filtration Flashcards
What is filtered by the kidneys?
Plasma not blood
What is the filtration barrier formed by anatomically?
- ) fenestrated vascular endothelium
- ) basement membrane
- ) podocytes
What are the podocytes separated by?
By slits in which they are called filtration slits because plasma is filtered between these slits. The slits are 25-60 nm wide and covered by a diaphragm.
What is the filtration barrier formed by chemically?
Proteins like collagen, laminin and other extracellular matrix proteins such as the negatively charged heparin sulphate proteoglycans.
This provides a charge barrier and has a sieving function.
What is the renal blood flow?
20 % of total cardiac output so 0.8-1 L/min
What is the renal plasma flow rate ?
since RBC is 40 % of blood, it is about 0.5-0.6 L / min
What is the glomerular filtration rate?
125 - 150 ml/min
How much primary urine its produced in a normal adult per day?
140 L of primary urine (135-180 is normal).
What is primary urine also called ?
Ultrafiltrate
Maintenance of a…….. glomerular filtration rate (GFR) is one of the most important regulated parameters in the kidneys
constant
what does glomerular ultra filtrate consist of?
water, small solutes, and normally protein free
The regulated reabsorption of water and solutes allows for regulation of what?
- ECF volume
- osmolality
- acid-base balance
- homeostasis pf whole body phosphate, calcium, and potassium concentration
What solutes are not fully reabsorbed or not absorbed at all?
urea, creatinine - freely filtered but not reabsorbed
Why is more creatinine excreted than filtered ?
because of secretion. We secrete some so that makes the percentage that we excrete 130 %.
The glomerular filtration barrier (GFB) is the most …… barrier in the body?
complex
Why is the GFB the most complex barrier?
- high filtration rates of water
- nonrestricted passage of small and middle sized molecules
- almost total restriction of serum albumin and larger proteins
- despite all the workload it remains intact for 80 + years.
Why are glomerular capillaries unique?
- because they have fenestrated area constituting of 20-50 % of the entire endothelial surface.
- It also facilitates high permeability.
- it is 60 nm in diameter whereas albumin only 3.6 nm hence endothelial cells do not determine the perm selectivity of the glomerular barrier.
What is perm selectivity?
a measure of the ability of a membrane to discriminate between anions and cations.
endothelial cell coat has ……..
charge selective properties
What side of the blood vessels is covered by endothelial cell surface layer?
The luminal side of blood vessel walls
What is endothelial cell surface layer comprised of?
negatively charged, glycolic proteins, glycosaminoglycans and membrane associated and secreted proteoglycans.
What contributes to the perm selectivity of the glomerular wall?
the ESL most likely because init is rather thick and negatively charged.
So what matters for a molecule that wants to pass through the membrane?
Size and charge
What is the glomerular basement membrane comprised of?
- A fibrous network with a backbone of type IV collagen.
- mutations in the collagen chains has shown to give rise to severe pathological conditions (alports syndrome)
- proteoglycans such as agrin and perlecan
- glycoproteins which contribute to the selective properties of the barrier
- the charge density within the glomerular barrier is derived from a combination of the endothelial cell layer and GBM
What are podocytes?
They are highly differentiated cells which line the outside of the glomerular capillaries and face the bowman’s space and primary urine.
What is the diaphragm of the podocytes composed of?
nephrin - when mutated can cause massive leakage of protein and severe consequences for patients (congenital nephrotic syndrome)
What is sieving (caused by the chemistry component of the basement membrane)?
- the basement membrane allows free passage for neutral molecules unto 6Kd MW (18 A radius). The negatively charged pores progressively restrict the passage of large (over 18 A) and almost completely sieve out neutral molecules that are larger than 40 A or smaller if negative (albumin).
In diseases, proteinuria may be because of loss of the negative charge selectivity or because of an increase in the number of large size pores.
What is the filtrate composition?
- small MW neutral solutes (less than 6Kd) have concentrations equal to that in the plasma because they are freely filtered
- larger sized molecules especially negatively charged solutes are sieved partially or completely.
- Hb appears in urine with 68 Kd when there is intravascular hemolysis but albumin doesn’t also with 68 Kd. Because of charges
What are the determinants of filtration?
movement of any molecule across the filtration membrane is measured by its flux.
Jv = k X S(change in P - oncotic pressure gradient)
Jv = Flux
k = Hydraulic conductivity
S = Surface area
P = Hydrostatic pressure gradient (gradient acting between the inside and outside of the capillary and bowman’s space)
Oncotic pressure gradient - oncoming pressure between eh inside and outside of the capillary and bowman’s space
What are the factors that effect the glomerular filtration rate?
GFR - the amount of filtrate formed per unit time
Determinants:
- Kf (ultrafiltration coefficient) X Pu (net ultrafiltration pressure)
Look at notes too much shit
