Wikipedia:Osmosis/Acute renal failure

Prerenal acute kidney injury
Acute kidney injury, or AKI, is when the kidney isn’t functioning at 100% and that decrease in function usually over a few days. Actually, AKI used to be known as acute renal failure, or ARF, but AKI is a broader term that also includes subtle decreases in kidney function. Prerenal means the cause of kidney injury’s coming before, or upstream from the kidneys, due to reduced blood flow into the kidneys.

The kidney’s job is to regulate what’s in the blood, things like removing waste, making sure electrolyte levels are steady, regulating the overall amount of water, and even making hormones - the kidneys do a lot! Blood gets into the kidney through the renal artery, into tiny clumps of arterioles called glomeruli where it is initially filtered, with the filtrate, the stuff filtered out, moving into the renal tubule. Sometimes fluid or electrolytes can move back from the filtrate into the blood - called reabsorption, and sometimes more fluid or electrolytes can move from the blood to the fitrate - called secretion. The kidneys also filter out waste-containing compounds like urea and creatinine, although some urea is actually reabsorbed back into the blood, whereas creatinine is only minimally reabsorbed. In fact, in the blood, the normal ratio of blood urea nitrogen, or BUN, to creatinine is between 5 and 20 to 1—meaning the blood carries 5 to 20 molecules of urea for every one molecule of creatinine, which becomes a good diagnostic for looking at kidney function! Ultimately the filtrate is turned into urine and is excreted from the kidney through the ureter, into the bladder, and peed away. Meanwhile, the filtered blood drains into the renal vein.

Prerenal kidney injury is due to a decreased blood flow into the kidneys. It could be due to an absolute loss of body fluid, like with major hemorrhage or blood loss, vomiting, diarrhea, or with severe burns where body fluid evaporates quickly without the protective skin. It could also be due to a relative loss of fluid, specifically a lower blood volume, meaning total body volume of water is the same, but less is in the circulatory system in the form of blood. One example of this is distributive shock, which is where fluid moves from the blood vessels into the tissues, keeping the total body fluid volume the same but with a relative decrease in blood volume. Another example is congestive heart failure because the heart’s inability to pump blood to the tissues means that more blood pools in the venous side and less is delivered to the kidneys. Finally, the issue could be local to the renal artery itself, for example, it could become narrowed, as in renal artery stenosis, or blocked by an embolus—a blood clot from somewhere else in the body.

In a prerenal situation, less blood going to the kidneys means less blood’s being filtered by the kidneys, so there’s a decrease in the glomerular filtration rate, or GFR, which is how much blood the kidneys filter through their glomeruli per minute. If less blood’s being filtered, and the GFR is lower, that means less urea and creatinine are filtered out, and people get azotemia—high levels of nitrogen-containing compounds in the blood, as well as oliguria, an abnormally low amount of urine production. With less blood being filtered, the kidneys also activate the renin-angiotensin system, which causes aldosterone release by the adrenal glands, and tells the kidneys to reabsorb sodium, which ultimately results in water reabsorption. Water and sodium reabsorption is tied to urea reabsorption, so in a prerenal situation, more urea gets reabsorbed into the blood, resulting in a BUN to creatinine ratio of greater than 20:1. More sodium and water being retained in the blood, means that the urine sodium is usually less than 20 mEq/L, that the fraction of sodium excreted to reabsorbed, or FENa, is usually less than 1%, and urine is more concentrated, typically greater than 500 mOsm/kg - most of which is urea (also why it smells so nitrogen-y when you’re dehydrated).

Postrenal acute kidney injury
Acute kidney injury, or AKI, is when the kidney isn’t functioning at 100% and that decrease in function usually over a few days. Actually, AKI used to be known as acute renal failure, or ARF, but AKI is a broader term that also includes subtle decreases in kidney function. Postrenal means the cause of kidney injury’s coming after, or downstream from the kidneys, usually because of an obstruction.

The kidney’s job is to regulate what’s in the blood, things like removing waste, making sure electrolyte levels are steady, regulating the overall amount of water, and even making hormones - the kidneys do a lot! Blood gets into the kidney through the renal artery, into tiny clumps of arterioles called glomeruli where it is initially filtered, with the filtrate, the stuff filtered out, moving into the renal tubule. Sometimes fluid or electrolytes can move back from the filtrate into the blood - called reabsorption, and sometimes more fluid or electrolytes can move from the blood to the fitrate - called secretion. The kidneys also filter out waste-containing compounds like urea and creatinine, although some urea is actually reabsorbed back into the blood, whereas creatinine is only minimally reabsorbed. In fact, in the blood, the normal ratio of blood urea nitrogen, or BUN, to creatinine is between 5 and 20 to 1—meaning the blood carries 5 to 20 molecules of urea for every one molecule of creatinine, which becomes a good diagnostic for looking at kidney function! Ultimately the filtrate is turned into urine and is excreted from the kidney through the ureter, into the bladder, and peed away. Meanwhile, the filtered blood drains into the renal vein.

Alright, so with postrenal AKI, there’s some obstruction to the outflow from the kidneys, in the ureters. Reduced flow can be a result of something compressing the ureter, like benign prostatic hyperplasia, a noncancerous growth of the prostate gland, or intra abdominal tumors that can push on the ureter. Also, it could be obstructed by something inside the ureter, like kidney stones.

The obstruction ultimately causes a buildup of pressure that back up all the way to the millions of tiny renal tubules. Since filtration moves fluid from the relatively high pressure arteriole to the low pressure renal tubule, increasing the renal tubule pressure reduces the pressure gradient and lowers the amount of fluid that filters across, lowering the GFR or glomerular filtration rate, which is how much blood the kidneys filter through their glomeruli per minute. This leaves people with azotemia or high levels of nitrogen-containing waste compounds like urea and creatinine in the blood, and oliguria—low levels of urine. Now if we follow the fluid that does make it into the tubule, it turns out that the high pressure tubular system essentially forces more reabsorption of fluid, sodium, and urea, again increasing the BUN to creatinine ratio in the blood, typically making it greater than 15 to 1. Also, while the tubules are functioning normally and reabsorbing appropriately, the urine concentration, urine sodium, and FENa are similar to prerenal AKI. I say “normally” because, over time, the increased pressure damages the epithelial cells responsible for reabsorption in the tubules. When that happens, less and less BUN gets reabsorbed back into the blood and instead gets dumped out into the urine, causing the BUN:Cr ratio to fall below 15 to 1. Also, decreased reabsorption of sodium and increased excretion of sodium causes urine sodium to go above 40 mEq/L and FENa to go above 1% in mild cases, and above 2% in severe cases, and causes urine osmolality to fall below 350 mOsm/kg.

Intrarenal acute kidney injury
Acute kidney injury, or AKI, is when the kidney isn’t functioning at 100% and that decrease in function usually over a few days. Actually, AKI used to be known as acute renal failure, or ARF, but AKI is a broader term that also includes subtle decreases in kidney function. Intrarenal, or sometimes intrinsic AKI, means that the AKI’s caused by the kidneys themselves, as opposed to prerenal and postrenal causes, which are upstream and downstream from the kidneys, respectively.

The kidney’s job is to regulate what’s in the blood, things like removing waste, making sure electrolyte levels are steady, regulating the overall amount of water, and even making hormones - the kidneys do a lot! Blood gets into the kidney through the renal artery, into tiny clumps of arterioles called glomeruli where it is initially filtered, with the filtrate, the stuff filtered out, moving into the renal tubule. Sometimes fluid or electrolytes can move back from the filtrate into the blood - called reabsorption, and sometimes more fluid or electrolytes can move from the blood to the fitrate - called secretion. The kidneys also filter out waste-containing compounds like urea and creatinine, although some urea is actually reabsorbed back into the blood, whereas creatinine is only minimally reabsorbed. In fact, in the blood, the normal ratio of blood urea nitrogen, or BUN, to creatinine is between 5 and 20 to 1—meaning the blood carries 5 to 20 molecules of urea for every one molecule of creatinine, which becomes a good diagnostic for looking at kidney function! Ultimately the filtrate is turned into urine and is excreted from the kidney through the ureter, into the bladder, and peed away. Meanwhile, the filtered blood drains into the renal vein.

Typically intrarenal AKI’s due to damage to the tubules, the glomerulus, or the interstitium. Let’s start with the most common cause of intrarenal AKI which is acute tubular necrosis, where the epithelial cells that line the tubules necrose, or die, typically because of either ischemia, a lack of blood supply to the cells, or via nephrotoxins, chemicals that are toxic to the epithelial cells.

Acute tubular necrosis due to ischemia is often preceded by prerenal acute kidney injury, since prerenal AKI results in less blood sent to the kidneys. All that secretion and reabsorption in the tubules takes a lot of energy, and so these cells are particularly sensitive to a loss of blood supply, especially the cells in the proximal tubule and medullary segment of the thick ascending limb. Nephrotoxins on the other hand, are substances that tend to damage the epithelial tubular cells. A few of the common ones being aminoglycosides—a group of antibiotics, heavy metals like lead, myoglobin released from damaged muscle, ethylene glycol—essentially anti-freeze which is naturally sweet tasting and therefore a risk for poisoning children, radiocontrast dye, and uric acid. That last one, uric acid, is a waste product that can build up when cells die during cancer treatment, called tumor lysis syndrome, and is the reason why staying well hydrated to improve flow through the tubules as well as using medications like allopurinol and urate oxidase to lower uric acid levels can be so important while on certain chemotherapy.

Whatever the cause of cell death, when those cells die, they slough off into the tubule, and basically build up and plug the tubule, which, similarly to postrenal AKI, generates higher pressures in the tubules, thereby lowering the GFR and causing azotemia and oliguria. Also, these dead cells clump up in the tubule and form a brown granular cast which will eventually get excreted in the urine. It’s called that because it’s basically a mold or cast of the tubule made up of dead cells. Those dead cells lose the ability to reabsorb molecules and the ability to remove and secrete molecules so they can be excreted in the urine, so other complications include hyperkalemia—buildup up potassium in the blood, and metabolic acidosis, a buildup of acid in the blood. If the underlying cause of the acute tubular necrosis is addressed, people can recover, because tubular cells can typically regenerate over the course of a few weeks.

Alright another type of intrarenal AKI is glomerulonephritis, or GN, which means inflammation of the glomerulus. GN is often caused by antigen-antibody complexes depositing in the glomerular tissue. This deposition activates the complement system, a cascade of enzymes that attracts other immune cells like macrophages and neutrophils to the site, which release lysosomal enzymes, causing inflammation and damaging the podocytes, the cells that line the glomerulus. These normally have small gaps between them and have a negative electrical charge, both of which prevents large molecules from filtering through. When damaged, therefore, membrane permeability increases and more large molecules are allowed to be filtered into the urine like red blood cells and proteins, called hematuria and proteinuria, respectively. Also this fluid leaking out reduces the hydrostatic pressure which drives filtration of small molecules and electrolytes like sodium, and so the GFR actually goes down because of the leakage. Lower GFR means less blood is being thoroughly filtered, which causes an increase in circulating volume which leads to edema or fluid buildup in the tissues, and hypertension from excess fluid volume. If more fluid’s retained, less urine gets produced and people get oliguria, low urine production. Finally, if less nitrogen-containing compounds are filtered out of the blood, there’s an increase in the blood, or azotemia.

Finally we have damage to the kidney interstitium as a cause of intrarenal AKI, one key example being acute interstitial nephritis, which is inflammation of the interstitium over the course of days to weeks. This inflammation is caused by infiltration of immune cells, like neutrophils and eosinophils, it’s thought to be a type I or type IV hypersensitivity reaction, and is typically a response to a medication like NSAIDs, penicillin, and diuretics. In addition to oliguria, people also tend to have general symptoms like a fever and a rash, as well as eosinophils in their urine and symptoms usually subside if the medication is stopped. If the medication isn’t removed, and the immune cells continue to damage the connective tissue, then those kidney cells can start to die off, called renal papillary necrosis, where the renal papillae are destroyed. This can again cause blood to be in the urine, or hematuria, and flank pain. Other potential causes of renal papillary necrosis are chronic use of analgesics, like aspirin, as well as diabetes mellitus, sickle cell disease, and pyelonephritis. In general, with intrarenal AKI, the kidneys lose the ability to filter the blood properly. If they can’t reabsorb urea, the BUN:Cr ratio falls to less than 15 to 1. Also, they can’t reabsorb sodium, meaning the urine Na+ goes above 40 mEq/L, and the fractional excretion of sodium, or FENa, the percent of sodium filtered that’s excreted in the urine, goes above 2%, and finally urine osmolality falls below 350 mOsm/kg. That’s it for intrarenal AKI, which is kidney injury caused by something within the kidneys themselves, which could be the tubules as in acute tubular necrosis, the glomerulus as in glomerulonephritis, or the interstitium as in acute interstitial nephritis.

Source
http://emedicine.medscape.com/article/238545-workup

http://www.uptodate.com/contents/etiology-and-diagnosis-of-prerenal-disease-and-acute-tubular-necrosis-in-acute-kidney-injury-acute-renal-failure

https://en.wikipedia.org/wiki/Azotemia