Renal: Renal Filtration 2 Flashcards
what are the steps for tubuloglomerular feedback
1- GFR increases
2- flow through tubules increases
3- flow past macula densa increases: inc NaCl = inc flow
4- paracrine diffusion from macula densa to afferent arteriole (adenosine)
5-afferent arteriole constricts
6-resistance in afferent arteriole increases
7- hydrostatic pressure in glomerulus decreases
8- GFR decreases
what is tubuloglomerular feedback
TGF: The adaptation of the GFR to changes in the characteristics of early distal tubule fluid through the modulation of local responses at the level of the individual nephron
what are the steps in osmotic sensing of filtrate for local control of blood flow in TGF
1: Uptake of Na+, K+, and Cl- by Na+-K+-2Cl- cotransporter in macula densa cells;
2: Generation of adenosine (ADO) involving 5’-nucleotidase;
3: ADO activates adenosine A1 receptors, triggering an increase in cytosolic Ca2+ in extraglomerular mesangial cells (MC);
4: Propagation of the increased Ca2+ signal, resulting in afferent arteriolar vasoconstriction and inhibition of renin secretion. Local angiotensin II (ANG II) and neuronal nitric oxide synthase (NOS I) activity modulate this response.
(afferent arteriolar vasoconstriction has a local effect; inhibition of renin secretion is a systemic effect bc its not part of TGF)
what does stable hydrostatic pressure in glomerular capillaries allow
Stable hydrostatic pressure in glomerular capillary allows maintenance of driving force for
filtration to occur under a wide range of systemic pressures. GFR is maintained at a relatively constant level as a result
order of vessels in renal
aorta/renal artery
interlobular artery
afferent arteriole
glomerular capillary
efferent arteriole
peritubular capillary
small renal veins
main renal vein
steps in renal response to changes in blood pressure/perfusion
1)
-reduced renal perfusion pressure
-myogenic reflex and TGF
-decreased resistance of afferent arteriole
-maintenance of GPF (glomerular perfusion)
2)
-reduced renal perfusion pressure
-angiotensin II released
-increased resistance of efferent arteriole
-maintanence of glomerular capillary pressure (from both 1) and 2) contribution)
BOTH = leads to the maintenance of GFR
how do you determine how well a filter like the glomerulus is working
- Find a substance that is filtered out and not reabsorbed (or secreted).
- Examine how much is present in the urine relative to how much is in the plasma over a period of time.
- This could be something we inject, or something the body makes at a relatively constant rate.
how can we determine GFR
by measuring concentration of a substance in the blood and in the urine that is filtered by the glomerulus and not reabsorbed and the volume of urine that is produced in that time
what is the concept of renal clearance and what substances do we use to measure filtration
For clearance to reflect filtration (eg. ONLY the function of the glomerulus), then the substance will have to be freely filtered and not re-absorbed or secreted into the tubule
Two “classic” substances to measure filtration are Inulin (a non-toxic injectable dye) and Creatinine (a metabolite). A recent, (POSSIBLY) more sensitive and accurate marker is Symmetric Dimethyl Arginine (SDMA).
what is creatinine level used in general practice
We don’t actually need to do an entire creatinine clearance (SDMA or inulin clearance) study for every case in regular practice because we know that, if the glomerulus isn’t working, the level of creatinine should rise. So instead, we roughly “estimate” GFR by simply determining whether creatinine falls in the normal range. If it is high, we typically conclude that glomerular filtration rate is decreased.
what is azotemia
An increase in creatinine, urea, SDMA and other nitrogenous waste products is called azotemia
pre renal vs renal azotemia
- Prerenal – Blood flow to glomerulus is decreased
- Renal (Intrinsic) – Fundamental problem with glomerulus (eg. decreased number of functioning glomeruli or decreased function of each glomerulus)
what is uremia
Uremia refers to the Clinical Signs observed with renal failure and increased BUN/Creatinine Azotemia
how to evaluate if the glomerulus is leaky vs if its filtering enough blood
- To evaluate whether the glomerulus is “leaky” – look for protein in the URINE (Note that this is not the ONLY cause of proteinuria, but it should be on the list of potential causes).
- To evaluate whether the patient’s glomeruli are collectively filtering enough blood (eg. GFR) – examine the BLOOD for BUN, Creatinine, SDMA (these are things that should be filtered out).
