If we are talking basic mechanisms, also include the increased distal delivery and alkalosis-producing effects (like taking diuretic), and internal dissociation curve via Henderson-Hasselbach, which will increase available sources of bicarb.
These are not the basic mechanisms of renal physiology...we gotta get more basic:
Autoregulation (
AR) and Tubuloglomerular feedback (
TGF).
ESRD is overwhelmingly caused by diabetes, and less frequently HTN (although both are usually present together). With glycation, arteriosclerosis, and atherosclerosis of the renal arterioles, the ability of the afferent arteriole to regulate glomerular capillary pressure is lost. The mechanism is incompletely understood (how wonderfully and frighteningly we are created), however the pathology is better appreciated. With the loss of auto reguation, the kidney is unable to compensate for wide swings in pressure, resulting in hyperfiltration at high renal perfusion pressures (with damage to the glomerular capillaries and basement membrane) and Acute Kidney Injury (formerly ARF) at low pressures. The dings and insults add up over the years with a decremental decline in GFR and elevation of the Cr to the new/diseased "set point."
TGF is the change in GFR mediated by the macula densa in response to a decreased filtered load of Na/Cl. TGF and AR are intertwined; a decrease in GFR results in a decreased filtered load sensed by the macula densa initiating a response returning GFR (and the filtered load) to normal. Again the mechanism is incompletely understood, but the main players are thought to be Renin (via AngII), Adenosine, Thromboxane, and NO. The primacy of any one mediator is still debatable. Nevertheless, the effective circulating volume (and subsequent renal perfusion pressure) is maintained by decreasing sodium excretion.
Distal delivery is irrelevant in a nonfunctioning nephron. Histologic examination of the nephron in chronic kidney disease reveals celluar necrosis and apoptosis. As such, there is little to no active transport and the counter-current multiplier is compromised. The only functional part of the nephron would be the most proximal segments...simply by sheer volume of transport. 2/3 of the filtered load is handled in the proximal convoluted tubule.
Further, taking a diuretic (furosemide) results in impairment of autoregulation as renal perfusion is increased, returning us to our two most basic mechanisms, TGF and AR. Loop diuretics reduce autoregulation ( and increase renal perfusion) by blocking the Na/K/2Cl transporter in the loop of Henle. This transporter, in addition to generating free water, transports Na/Cl across the tubular cell to the macula densa. By blocking intracellular transport at this critical spot, there is reduced TGF (and AngII) reducing the effective circulating volume.
Point that has not been addressed, and the entire premise of the post is whether this can occur in a patient with known end stage renal disease.
Any takers on the latter (or initial) question?
Still going with redundancy and aforementioned mechanisms.
In ESRD, the tubular cells are dead or dying, active transport is compromised, and AR and TGF is disrupted. So, using barely understood physiologic concepts to describe a pathologic process seems silly.
I would surmise that the phenomenon of contraction alkalosis in these individuals is highly variable, depending mostly on the residual renal function of the individual patient. Many ESRD patients
do make urine (remember that anuria is not one of the absolute indications for dialysis...
AEIOU), as such, many of these individuals would be expected to have some residual functional HCO3/Cl transporters in the PCT.
Sorry this got choppy near the end, but I gotta meet some buddies for beers.
