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Acute kidney injury, or AKI, is when the kidney
isn’t functioning at 100% and that decrease
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in function develops relatively quickly, typically
over a few days.
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Actually, AKI used to be known as acute renal
failure, or ARF, but AKI is a broader term
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that also includes subtle decreases in kidney
function.
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AKI can essentially be split into three types,
prerenal AKI meaning the cause of kidney injury’s
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coming before the kidneys, postrenal AKI—meaning
after the kidneys, or intrarenal AKI—meaning
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within the kidneys.
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Now the kidney’s job is to regulate what’s
in the blood, so they might remove waste,
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or make sure electrolyte levels are steady,
or regulate the overall amount of water, and
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even make hormones - the kidneys do a lot
of stuff!
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Blood gets into the kidney through the renal
artery, into tiny clumps of arterioles called
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glomeruli where it’s initially filtered,
with the filtrate, the stuff filtered out,
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moving into the renal tubule.
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Sometimes fluid or electrolytes can move back
from the filtrate into the blood - called
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reabsorption, and sometimes more fluid or
electrolytes can move from the blood to the
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fitrate - called secretion.
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Along with fluid and electrolytes, though,
waste-containing compounds are also filtered,
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like urea and creatinine, although some urea
is actually reabsorbed back into the blood,
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whereas only a little bit of creatinine is
reabsorbed.
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In fact, in the blood, the normal ratio of
blood urea nitrogen, or BUN, to creatinine
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is between 5 and 20 to 1—meaning the blood
carries 5 to 20 molecules of urea for every
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one molecule of creatinine, and this is a
pretty good diagnostic for looking at kidney
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function!
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Ultimately the filtrate is turned into urine
and is excreted from the kidney through the
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ureter, into the bladder, and peed away.
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Meanwhile, the filtered blood drains into
the renal vein.
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Typically intrarenal AKI’s due to damage
to the tubules, the glomerulus, or the interstitium—the
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space between tubules.
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Starting with the tubules and the most common
cause of intrarenal AKI, which is acute tubular
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necrosis.
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Which is where the epithelial cells that line
the tubules necrose, or die.
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One way this can happen is via ischemia, or
a lack of blood supply to the cells.
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A lot of times acute tubular necrosis due
to ischemia is caused by some prerenal acute
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kidney injury, since prerenal AKI results
in less blood sent to the kidneys, and those
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epithelial cells need oxygen from the blood
just like any other cells.
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In fact, all that secretion and reabsorption
in the tubules takes a lot of energy, and
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so these cells are particularly sensitive
to a loss of blood supply, especially the
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cells in the proximal tubule and medullary
segment of the thick ascending limb.
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The other way epithelial cells can necrose
is via nephrotoxins, which are substances
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that tend to damage the epithelial tubular
cells.
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A few of the common ones being aminoglycosides—a
group of antibiotics, heavy metals like lead,
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myoglobin released from damaged muscles, ethylene
glycol—essentially anti-freeze which is
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naturally sweet tasting and therefore a risk
for poisoning children, radiocontrast dye,
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and uric acid.
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That last one, uric acid, is a waste product
that can build up when cells die during cancer
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treatment, called tumor lysis syndrome, and
is the reason why staying well hydrated to
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improve flow through the tubules as well as
using medications like allopurinol and urate
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oxidase to lower uric acid levels can be so
important while on certain chemotherapy.
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Whatever the cause of cell death is, when
those cells die, they slough off into the
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tubule, and basically build up and plug the
tubule, which, just like in postrenal AKI,
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generates higher pressures in the tubules,
which means fluid’s essentially trying to
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flow from high pressure arterioles to high
pressure tubules...which doesn’t really
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work very well and the fluid filtered across
is lowered, which lowers the glomerular filtration
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rate or GFR, which is how much blood the kidneys
filter in mL through their glomeruli per minute.
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With less blood being filtered, less urine
is produced, called oliguria, abnormally low
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urine production, and less urea and creatinine
get filtered out, so more stays in the blood,
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called azotemia, high levels of nitrogen-containing
compounds in the blood.
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Along with that, dead cells aren’t very
good at reabsorbing or secreting molecules
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anymore, right?
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So other things start to build up in the blood
as well, like potassium, called hyperkalemia,
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as well as acids, called metabolic acidosis.
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Also, these dead clumped up cells in the tubule
form a brown granular cast which will eventually
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get excreted in the urine.
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It’s called a cast because it stays in essentially
the same cylindrical shape as the tubule.
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If the underlying cause of the acute tubular
necrosis is addressed, people can recover,
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because tubular cells can typically regenerate
over the course of a few weeks.
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Alright another type of intrarenal AKI is
glomerulonephritis, or GN, which means inflammation
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of the glomerulus.
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GN is often caused by antigen-antibody complexes
depositing in the glomerular tissue.
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This deposition activates the complement system,
which is a cascade of enzymes that attracts
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other immune cells like macrophages and neutrophils
to the site, which release lysosomal enzymes,
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causing inflammation and damaging the podocytes,
which are the cells that line the glomerulus.
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These normally have small gaps between them
and have a negative electrical charge, both
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of which prevents large molecules from filtering
through.
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When damaged, therefore, membrane permeability
increases and large molecules are allowed
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to be filtered into the urine proteins, called
proteinuria, and even red blood cells, called
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hematuria.
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Also this fluid leakage reduces the pressure
difference that drives filtration of small
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molecules and electrolytes like sodium, and
so the GFR actually goes down because of the
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leakage.
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Lower GFR means less blood gets filtered and
so less urine’s produced, causing oliguria,
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and that also means more fluid circulating
in the blood, which leads to edema or fluid
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buildup in the tissues, as well as hypertension
from excess fluid volume.
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Finally, if those nitrogen-containing compounds
aren’t being filtered out, more stays in
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the blood, which causes azotemia.
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Alright, finally we have damage to the kidney
interstitium as a cause of intrarenal AKI,
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one key example being acute interstitial nephritis,
which is inflammation of the interstitium
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over the course of days to weeks.
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This inflammation is caused by infiltration
of immune cells, like neutrophils and eosinophils,
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which then cause inflammation.
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This is thought to be a type I or type IV
hypersensitivity reaction, and is typically
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a response to a medication like NSAIDs, penicillin,
and diuretics.
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Early symptoms include oliguria and eosinophiluria,
which is eosinophils in the urine, but also
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general symptoms like a fever and a rash.
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These symptoms usually subside if the medication
is stopped.
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But if the medication isn’t removed, and
the immune cells continue to damage the connective
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tissue in the interstitium, and those kidney
cells can start to die off, called renal papillary
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necrosis, where the renal papillae are destroyed.
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This can again cause hematuria, blood in the
urine, as well as flank pain.
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Other potential causes of renal papillary
necrosis are chronic use of analgesics, like
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aspirin, as well as diabetes mellitus, sickle
cell disease, and pyelonephritis.
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In general, with intrarenal AKI, the kidneys
lose the ability to filter the blood properly,
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and the cells are often damaged such that
reabsorption and secretion are impaired.
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If the urea isn’t reabsorbed, less urea
stays in the blood relative to creatinine,
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and the BUN:Cr ratio falls to less than 15
to 1.
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Also, those cells can’t reabsorb sodium,
meaning the urine Na+ goes above 40 mEq/L,
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and the FENa, which is the fraction of sodium
excreted in the urine, of total sodium filtered,
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expressed as a percentage, goes above 2%,
and finally since water’s not being reabsorbed
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as much, urine osmolality falls below 350
mOsm/kg.
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So as a quick recap, intrarenal AKI is kidney
injury caused by something within the kidneys
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themselves, which could be the tubules as
in acute tubular necrosis, the glomerulus
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as in glomerulonephritis, or the interstitium
as in acute interstitial nephritis.
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Now that you know all about intrarenal AKI,
check out these other two videos on prerenal
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AKI and postrenal AKI!
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