Tubulointerstitial Diseases

Before we get to the actual Tubulointerstitial Diseases themselves, lets talk about what the Tubulointerstitium is and a bit about Acute Renal Failure which is what Tubulointerstitial Diseases can lead to. 

Tubulointerstitium

·         consists of:

o        compactly arranged tubules with acellular interstitium

o        efferent arteriole derived peritubular vascular network (in the cortex) and the vasa recta (see pic on right) which is also derived from the efferent arteriole and found in the medulla.

o        There is segmental variation in tubular epithelial cell structure – this is why toxins only affect certain parts of the tubules – more on this later.

·         Proximal tubules are more metabolically active and hence are more susceptible to injury

Acute Renal Failure

(ARF …not BARF which is what this lecture probably made everyone wanna do) 

• Acute renal failure is a clinical syndrome characterized by rapid deterioration of renal function over a relatively short period of time and is a result of a variety of pathologic entities.
• Some stats:
  • 1% of the admitted patients have Acute Renal Failure at admission
  • 2-5 % of Acute Renal Failure cases occur during hospitalization
  • 15% of patients undergoing cardiopulmonary bypass end up with Acute Renal Failure
     

• Types of Acute Renal Failure
• Pre-renal azotemia – There is nothing wrong with the kidneys in these situations, however, the state that the patient is in manifests itself as renal disorders.  It usually involves renal hypoperfusion from decreased cardiac output.  Therefore, there is decreased glomerular filtration and renal insufficiency.

• Examples of pre-renal Acute Renal Failure:
  • CHF and Shock
  • Hypovolemic states – for example, say you have a child that is vomiting and having severe diarrhea.  The child is losing a lot of water, therefore, the body is not producing any urine.  There is nothing wrong with the kidneys themselves – the cause of the renal insufficiency is that the child is dehydrated, there is volume depletion.

• Intra-renal Acute Renal Failure – These are the disorders we are going to be dealing with the most.  Intra-renal Acute Renal Failure is due to the pathology of the kidneys themselves.
  • Examples of intra-renal Acute Renal Failure:
    • Acute renal tubular necrosis
    • Severe acute proliferative glomerulonephritis, especially Crescentic glomerulonephritis (RPGN)
    • Severe tubulo-interstitial nephritis
    • Malignant hypertension, thrombotic microangiopathy, thromboembolism
    • Acute & chronic pyelonephritis
    • Acute papillary necrosis
    • Bilateral renal cortical necrosis
• Post-renal azotemia – These are characterized by an obstructive uropathy.  There is an obstruction to renal flow distal to the kidneys themselves.  Like the pre-renal Acute Renal Failure, there isn’t anything wrong with the actual kidneys.
  • Examples of post-renal Acute Renal Failure:
    • Prostatic hypertrophy – This can occur with elderly patients who cannot pass urine because their prostate is enlarged.
    • Lower urinary tract obstruction – like stones, strictures, and neoplasia

 
Tubular Structure and Function 

• The proximal tubules have a brush border and a lot of mitochondria, and therefore, produce a lot of enzymes.  Because of this, these cells are very sensitive to hypoxia, toxins, and injury.  Downstream areas of the nephron are progressively less sensitive.  Therefore, you see a varying distribution of acute tubular injury due to hypoxia or toxins in the tubules.
• When you look at the filtration in the proximal tubule – the cells reabsorb from the filtrate and secrete from the interstitial blood vessel into the lumen.  Therefore, there is a two way flow across the tubular epithelial cells.
  • So, if there is some toxin present, like carbon tetrachloride, it will be concentrated in the tubular epithelial cells because of this two way flow.
  • The result is that the concentration gradient of the toxin between the epithelial cells and filtrate is very wide.  The toxin is highly concentrated in the epithelial cells, which makes these cells very prone to injury.
• This is why the kidneys face the brunt of the damage due to toxin ingestion - because the kidneys concentrate the toxin within the tubular cells.
• In the distal tubule, there is more concentration of the toxin (in post-secretory reabsorption).

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