Let's use this visual to discuss some events in chronic renal disease
Yes, the "pitted" surface of the kidney is indicative of scarring. Since scars are composed of fibrous connective tissue, the lesion is CHRONIC! Is there another indication of chronicity in this visual?
Most animals with renal failure have hyperphosphatemia; because the GFR is decreased, phosphorus is no longer secreted adequately. The excess phosphorus binds up calcium in the serum, lowering ionized calcium. With reduced ionized calcium, parathyroid hormone (PTH; parathormone) secretion is stimulated, causing calcium to be released from readily mobilized stores in the bone (osteoclastic bone resorption). On the other hand, diseased kidneys have a reduced ability to synthesize calcitriol (the active form of Vitamin D). Decreased hydroxylation from 25-hydroxycholescalciferol to calcitriol leads to decreased intestinal absorption of calcium. In addition, calcitriol normally suppresses PTH secretion, such that reduced calcitriol levels further increases PTH secretion. With time, this results in parathyroid hyperplasia (renal secondary hyperparathyroidism). Other associated conditions include fibrous osteodystrophy (renal osteodystrophy) and soft tissue mineralization.
Most dogs in renal failure do not develop clinically evident fibrous osteodystrophy as depicted above. It does occur in some cases of chronic renal failure.
This is an example of mineralization secondary to renal failure and uremia. The left atrium (as seen here) is a common sight of soft tissue mineralization in renal disease.
Does mineralization occur elsewhere in chronic renal disease?
There are two possible mechanism to explain soft tissue mineralization associated with renal disease. One mechanism is METASTATIC MINERALIZATION - there is excess Ca and P in the blood - the two combine and form mineral deposits in tissues near the site where they first combine. In this pathogenesis, the mineral calcium phosphate forms due to excess levels of calcium and phosphorus in the blood.Most experts believe another mechanism is more likely.
It is more likely that cells or tissues are injured FIRST and then become mineralized SECONDARILY. This process is called DYSTROPHIC MINERALIZATION. For instance, the stomach mucosal cells may be injured by a "uremic toxin"- the toxin is not known (it might even be the excessive Ca or P levels or parathormone itself). Once the cells are injured, a cascade of events occurs which results in mineral deposition within the injured and dead cells or tissue.
Do you remember another serious problem that occurs in the stomach secondarily to renal failure?
This is an example of FIBRIN deposition in the wall of this gastric artery (so called FIBRINOID NECROSIS). In uremic animals, vasculopathy and coagulopathy are seen. A common sequela is thrombosis, vascular obstruction and ischemic necrosis of the mucosa supplied by the affected branch of the artery.
Another lesion commonly associated with renal failure is shown below.
Oral ulcers and ulcerative glossitis may result from acute or chronic renal failure.
Again looking at this kidney, let's discuss another consequence of renal failure. We have said the surface is pitted and scarred. What does this indicate is happening to nephrons?
Remember the cardinal principle though; A LOST NEPHRON IS NEVER REPLACED WITH A NEWLY REGENERATED NEPHRON - we have a finite number of nephrons (we never get new ones!). So compensation can occur within limits, but at a certain point the number of nephrons lost exceeds the ability of the remaining nephrons to compensate by hypertrophy. What happens at this point?
Answer - ENDSTAGE KIDNEY
The term ENDSTAGE KIDNEY is used to describe renal disease which is chronic, advanced, generalized, progressive and irreversible. The term was adopted because of the inability to differentiate antecedent causes of "end stage kidneys". See the example below:
In other words, the cause may have been glomerular, tubular, vascular, or interstitial - but the final gross appearance is the same because fibrosis results from all of these causes. Note these kidneys are scarred and fibrotic - the cortex is nearly absent in some areas.
In the example below, the end stage kidney was due to chronic glomerular disease. However, we cannot tell the cause was glomerular by examination of a kidney at this late stage of disease.
How about the NEPHROTIC SYNDROME. Proceed to the next section to learn about the nephrotic syndrome.
Q1: What are the three forms of azotemia?
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ANSWER: Pre-renal, renal, and post-renal.
Q2: List three reasons why the urine might be red. Click here for answer.
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ANSWER: Blood, hemoglobin and myoglobin.
Q3: Outline the pathogenesis of these photographs taken at necropsy of a 13-yr-old dog.
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ANSWER: Renal fibrosis (end stage kidney) -> chronic renal failure -> hyperphosphatemia and depressed serum CA -> hyperparathyroidism -> pleural mineralization (metastatic calcification)
Renal fibrosis (end stage kidney) -> chronic renal failure -> uremic tissue damage coupled with increased serum phosphorus and Ca levels -> pleural mineralization (dystrophic calcification)
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