Intrarenal acute kidney injury (acute renal failure) - causes, symptoms & pathology

00:09:33
https://www.youtube.com/watch?v=ISFEgK8sfb8

Resumo

TLDRThe video provides an overview of acute kidney injury (AKI), focusing specifically on intrarenal AKI, which occurs due to direct damage within the kidneys. AKI is characterized by a rapid decline in kidney function and can be categorized into prerenal, postrenal, and intrarenal types. Intrarenal AKI includes conditions such as acute tubular necrosis, often caused by ischemia or nephrotoxins; glomerulonephritis, which involves inflammation of the glomerulus due to immune complex deposition; and acute interstitial nephritis, typically triggered by hypersensitivity reactions to various medications. Each condition affects the kidney's ability to filter blood and maintain electrolyte balance, leading to symptoms such as oliguria, azotemia, potassium build-up, metabolic acidosis, and sometimes the excretion of blood and proteins in urine. Treatments focus on addressing the underlying cause and allowing kidney cells to regenerate when possible.

Conclusões

  • 🩺 AKI affects the kidney's ability to function properly.
  • 🔍 AKI is categorized into prerenal, postrenal, and intrarenal types.
  • 💀 Intrarenal AKI can be caused by tubular damage, glomerular inflammation, or interstitial problems.
  • 🧪 Acute tubular necrosis often results from ischemia or exposure to nephrotoxins.
  • 🛡️ Glomerulonephritis involves immune-related damage to the glomerulus.
  • 💊 Acute interstitial nephritis can be a hypersensitivity reaction to drugs.
  • 🔬 Chemical imbalances in the blood indicate kidney function issues.
  • 🚱 Oliguria is a common symptom due to reduced urine production.
  • ⚗️ Azotemia occurs when nitrogen waste accumulates in the blood.
  • ⚖️ Treatments focus on resolving the underlying cause and supporting recovery.

Linha do tempo

  • 00:00:00 - 00:09:33

    Acute kidney injury (AKI) refers to a rapid decline in kidney function, characterized by a reduction in the ability of the kidneys to regulate blood content. AKI is classified into prerenal, postrenal, and intrarenal types. Intrarenal AKI often results from acute tubular necrosis, glomerulonephritis, or acute interstitial nephritis and impairs the kidney's filtration capacity. Acute tubular necrosis, the most common cause of intrarenal AKI, involves ischemia-induced or nephrotoxin-induced death of tubular epithelial cells. Glomerulonephritis involves immune-mediated damage to the glomeruli, resulting in proteinuria and hematuria, while acute interstitial nephritis results from immune cell infiltration due to drug hypersensitivity. Consequently, the kidney’s capacities for reabsorption and secretion are diminished, affecting key metabolic processes and potentially causing elevated blood nitrogen levels and imbalances in electrolyte and fluid homeostasis. Recovery from some intrarenal AKI causes is possible if underlying issues are addressed.

Mapa mental

Vídeo de perguntas e respostas

  • What is acute kidney injury (AKI)?

    AKI is a condition where the kidney's function decreases rapidly, usually over a few days.

  • What are the types of AKI?

    AKI can be classified into prerenal, postrenal, and intrarenal types.

  • What causes intrarenal AKI?

    Intrarenal AKI can be caused by damage to the tubules, the glomerulus, or the interstitium.

  • What is acute tubular necrosis?

    It is a common cause of intrarenal AKI where epithelial cells in the tubules die due to ischemia or nephrotoxins.

  • What is glomerulonephritis?

    Glomerulonephritis is inflammation of the glomerulus often caused by antigen-antibody complexes.

  • What causes acute interstitial nephritis?

    It is caused by inflammation in the interstitium often due to hypersensitivity reactions to medications.

  • What are nephrotoxins?

    Nephrotoxins are substances that damage tubular epithelial cells, such as certain antibiotics, heavy metals, and contrast dyes.

  • How does ischemia cause acute tubular necrosis?

    Ischemia restricts blood flow, depriving cells of oxygen necessary for energy-intensive functions.

  • What are the symptoms of acute interstitial nephritis?

    Early symptoms include oliguria, eosinophiluria, fever, and rash.

  • What happens during glomerulonephritis?

    The inflammation causes damage to podocytes, resulting in proteinuria, hematuria, and decreased GFR.

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  • 00:00:04
    Acute kidney injury, or AKI, is when the kidney isn’t functioning at 100% and that decrease
  • 00:00:09
    in function develops relatively quickly, typically over a few days.
  • 00:00:14
    Actually, AKI used to be known as acute renal failure, or ARF, but AKI is a broader term
  • 00:00:21
    that also includes subtle decreases in kidney function.
  • 00:00:24
    AKI can essentially be split into three types, prerenal AKI meaning the cause of kidney injury’s
  • 00:00:30
    coming before the kidneys, postrenal AKI—meaning after the kidneys, or intrarenal AKI—meaning
  • 00:00:38
    within the kidneys.
  • 00:00:40
    Now the kidney’s job is to regulate what’s in the blood, so they might remove waste,
  • 00:00:45
    or make sure electrolyte levels are steady, or regulate the overall amount of water, and
  • 00:00:49
    even make hormones - the kidneys do a lot of stuff!
  • 00:00:53
    Blood gets into the kidney through the renal artery, into tiny clumps of arterioles called
  • 00:00:58
    glomeruli where it’s initially filtered, with the filtrate, the stuff filtered out,
  • 00:01:03
    moving into the renal tubule.
  • 00:01:06
    Sometimes fluid or electrolytes can move back from the filtrate into the blood - called
  • 00:01:10
    reabsorption, and sometimes more fluid or electrolytes can move from the blood to the
  • 00:01:15
    fitrate - called secretion.
  • 00:01:18
    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,
  • 00:01:29
    whereas only a little bit of creatinine is reabsorbed.
  • 00:01:31
    In fact, in the blood, the normal ratio of blood urea nitrogen, or BUN, to creatinine
  • 00:01:37
    is between 5 and 20 to 1—meaning the blood carries 5 to 20 molecules of urea for every
  • 00:01:43
    one molecule of creatinine, and this is a pretty good diagnostic for looking at kidney
  • 00:01:48
    function!
  • 00:01:50
    Ultimately the filtrate is turned into urine and is excreted from the kidney through the
  • 00:01:54
    ureter, into the bladder, and peed away.
  • 00:01:57
    Meanwhile, the filtered blood drains into the renal vein.
  • 00:02:02
    Typically intrarenal AKI’s due to damage to the tubules, the glomerulus, or the interstitium—the
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    space between tubules.
  • 00:02:09
    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.
  • 00:02:21
    One way this can happen is via ischemia, or a lack of blood supply to the cells.
  • 00:02:26
    A lot of times acute tubular necrosis due to ischemia is caused by some prerenal acute
  • 00:02:31
    kidney injury, since prerenal AKI results in less blood sent to the kidneys, and those
  • 00:02:36
    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
  • 00:02:50
    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
  • 00:03:00
    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
  • 00:03:16
    naturally sweet tasting and therefore a risk for poisoning children, radiocontrast dye,
  • 00:03:22
    and uric acid.
  • 00:03:23
    That last one, uric acid, is a waste product that can build up when cells die during cancer
  • 00:03:28
    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
  • 00:03:37
    oxidase to lower uric acid levels can be so important while on certain chemotherapy.
  • 00:03:44
    Whatever the cause of cell death is, when those cells die, they slough off into the
  • 00:03:48
    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
  • 00:03:58
    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.
  • 00:04:32
    Along with that, dead cells aren’t very good at reabsorbing or secreting molecules
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    anymore, right?
  • 00:04:37
    So other things start to build up in the blood as well, like potassium, called hyperkalemia,
  • 00:04:42
    as well as acids, called metabolic acidosis.
  • 00:04:45
    Also, these dead clumped up cells in the tubule form a brown granular cast which will eventually
  • 00:04:51
    get excreted in the urine.
  • 00:04:53
    It’s called a cast because it stays in essentially the same cylindrical shape as the tubule.
  • 00:04:59
    If the underlying cause of the acute tubular necrosis is addressed, people can recover,
  • 00:05:04
    because tubular cells can typically regenerate over the course of a few weeks.
  • 00:05:09
    Alright another type of intrarenal AKI is glomerulonephritis, or GN, which means inflammation
  • 00:05:14
    of the glomerulus.
  • 00:05:15
    GN is often caused by antigen-antibody complexes depositing in the glomerular tissue.
  • 00:05:21
    This deposition activates the complement system, which is a cascade of enzymes that attracts
  • 00:05:26
    other immune cells like macrophages and neutrophils to the site, which release lysosomal enzymes,
  • 00:05:32
    causing inflammation and damaging the podocytes, which are the cells that line the glomerulus.
  • 00:05:38
    These normally have small gaps between them and have a negative electrical charge, both
  • 00:05:42
    of which prevents large molecules from filtering through.
  • 00:05:46
    When damaged, therefore, membrane permeability increases and large molecules are allowed
  • 00:05:50
    to be filtered into the urine proteins, called proteinuria, and even red blood cells, called
  • 00:05:56
    hematuria.
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    Also this fluid leakage reduces the pressure difference that drives filtration of small
  • 00:06:02
    molecules and electrolytes like sodium, and so the GFR actually goes down because of the
  • 00:06:09
    leakage.
  • 00:06:10
    Lower GFR means less blood gets filtered and so less urine’s produced, causing oliguria,
  • 00:06:14
    and that also means more fluid circulating in the blood, which leads to edema or fluid
  • 00:06:19
    buildup in the tissues, as well as hypertension from excess fluid volume.
  • 00:06:24
    Finally, if those nitrogen-containing compounds aren’t being filtered out, more stays in
  • 00:06:29
    the blood, which causes azotemia.
  • 00:06:32
    Alright, finally we have damage to the kidney interstitium as a cause of intrarenal AKI,
  • 00:06:38
    one key example being acute interstitial nephritis, which is inflammation of the interstitium
  • 00:06:43
    over the course of days to weeks.
  • 00:06:46
    This inflammation is caused by infiltration of immune cells, like neutrophils and eosinophils,
  • 00:06:51
    which then cause inflammation.
  • 00:06:52
    This is thought to be a type I or type IV hypersensitivity reaction, and is typically
  • 00:06:57
    a response to a medication like NSAIDs, penicillin, and diuretics.
  • 00:07:03
    Early symptoms include oliguria and eosinophiluria, which is eosinophils in the urine, but also
  • 00:07:10
    general symptoms like a fever and a rash.
  • 00:07:13
    These symptoms usually subside if the medication is stopped.
  • 00:07:15
    But if the medication isn’t removed, and the immune cells continue to damage the connective
  • 00:07:20
    tissue in the interstitium, and those kidney cells can start to die off, called renal papillary
  • 00:07:25
    necrosis, where the renal papillae are destroyed.
  • 00:07:27
    This can again cause hematuria, blood in the urine, as well as flank pain.
  • 00:07:34
    Other potential causes of renal papillary necrosis are chronic use of analgesics, like
  • 00:07:38
    aspirin, as well as diabetes mellitus, sickle cell disease, and pyelonephritis.
  • 00:07:44
    In general, with intrarenal AKI, the kidneys lose the ability to filter the blood properly,
  • 00:07:51
    and the cells are often damaged such that reabsorption and secretion are impaired.
  • 00:07:56
    If the urea isn’t reabsorbed, less urea stays in the blood relative to creatinine,
  • 00:08:02
    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,
  • 00:08:13
    and the FENa, which is the fraction of sodium excreted in the urine, of total sodium filtered,
  • 00:08:19
    expressed as a percentage, goes above 2%, and finally since water’s not being reabsorbed
  • 00:08:24
    as much, urine osmolality falls below 350 mOsm/kg.
  • 00:08:30
    So as a quick recap, intrarenal AKI is kidney injury caused by something within the kidneys
  • 00:08:36
    themselves, which could be the tubules as in acute tubular necrosis, the glomerulus
  • 00:08:40
    as in glomerulonephritis, or the interstitium as in acute interstitial nephritis.
  • 00:08:47
    Now that you know all about intrarenal AKI, check out these other two videos on prerenal
  • 00:08:51
    AKI and postrenal AKI!
  • 00:08:54
    Thanks for watching, you can help support us by donating on patreon, or subscribing
  • 00:09:08
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Etiquetas
  • AKI
  • Intrarenal AKI
  • Acute Tubular Necrosis
  • Glomerulonephritis
  • Acute Interstitial Nephritis
  • Ischemia
  • Nephrotoxins
  • Kidney Damage
  • Oliguria
  • Azotemia