Term
| what characterizes nephritic syndrome? |
|
Definition
| hematuria with RBC casts, variable proteinuria (nonnephrotic to nephrotic), diminished GFR, some degree of oliguria, azotemia, HTN |
|
|
Term
| what are nephritic syndromes usually caused by? |
|
Definition
| diseases that evoke an inflammatory proliferation response within the glomeruli |
|
|
Term
| what cells are usually involved with proliferation that happens in nephritic syndromes? |
|
Definition
| endothelial, mesangial, or epithelial cells |
|
|
Term
| are neutrophils present in nephritic syndrome? |
|
Definition
| they may be, especially with the post-infectious type |
|
|
Term
| what are the primary types of nephritic syndrome? |
|
Definition
| infectious glomerulonephritis, rapidly progressing glomerulonephritis, and IgA (berger's)/henoch-schonlein purpura, and systemically: SLE and vasculitis |
|
|
Term
| what characterizes nephrotic syndrome? |
|
Definition
| massive proteinuria (daily loss of 3.5 g or more), hypoalbuminemia (plasma albumin <3gm/dl), generalized edema (if don’t have protein to allow for fluid to remain in vasculature and it can leak out and lead to edema), and hyperlipidemia (no proteins to make lipoproteins)/lipiduria (if you see these, think nephrotic syndrome) |
|
|
Term
| what is the underlying etiology of nephrotic syndrome? |
|
Definition
| derangement in the glomerular capillary causing increased permeability to plasma proteins - resulting in massive proteinuria, which then leads to depletion of serum albumin and edema due to loss of colloid osmotic pressure (soft and pitting seen mostly in periorbital areas and dependent parts of the body). Na+ and H2O retention aggravates the edema. |
|
|
Term
| how does the hyperlipidemia associated with nephrotic syndrome manifest itself? |
|
Definition
| cholesterol levels are increased, VLDL/triglyceride levels are increased, and HDL levels are increased. |
|
|
Term
| how does nephrotic syndrome result in an increased level of lipoproteins? |
|
Definition
| the liver over-synthesizes more lipoproteins due to the primary hypoproteinemia as well as over-decreases their catabolism |
|
|
Term
| how does nephrotic syndrome result in lipiduria? |
|
Definition
| this occurs when lipoprotiens leak across the glomerular capillary wall |
|
|
Term
| what kinds of infections are pts with nephrotic syndrome prone to? why? |
|
Definition
| staph and pneumococci - perhaps due to loss of Igs and complement in the urine |
|
|
Term
| why are thrombi and thromboemboli common in nephrotic syndrome pts? |
|
Definition
| this is due to loss of anticoagulant factors through the leaky glomerulus associated with renal vein thrombi |
|
|
Term
| what are common causes of nephrotic syndrome? |
|
Definition
| membranous glomerulopathy, minimal change disease, FSGS, membranoproliferative GN, DM, amyloidosis, SLE, drugs, infections (hep B,C, syphilis, AIDs), and malignancies (CA and lymphoma) |
|
|
Term
| what is the most common cause of nephrotic syndrome in *non-DM adults*? what causes this specifically? |
|
Definition
| membranous glomerulopathy - which is mostly idiopathic. it can be caused secondarily by SLE, drugs, malignancy, hep B/C, and other autoimmune disorders |
|
|
Term
| what is the pathogenesis of membranous glomerulopathy? |
|
Definition
| the deposition of immune complexes on the *epithelial side of the GBM*, usually the antigen cannot be identified, but known antigens include tumors, hep B/C, SLE, and drugs |
|
|
Term
| how does membranous glomerulopathy appear under LM? IF? EM? |
|
Definition
| LM: slightly enlarged spikes are seen on *silver stain, eventually the glomeruli become sclerotic and hyalinized. IF: granular deposits of IgG and C3 along the GBM, in *secondary MGN, there may be mesangial deposits. EM: subepithelial deposits (dome) with spikes protruding of GBM around the deposits |
|
|
Term
| what is minimal change disease? |
|
Definition
| also called nil disease or lipoid nephrosis, minimal change disease is the most frequent cause of nephrotic syndrome in children. it is called so b/c on LM, the glomeruli look normal. |
|
|
Term
| does minimal change disease affect one gender more? |
|
Definition
|
|
Term
| is renal function preserved in minimal change disease? is HTN an effect? |
|
Definition
| renal function is usually preserved and HTN is not an effect of minimal change disease |
|
|
Term
| can minimal change disease cause acute renal failure in adults? |
|
Definition
|
|
Term
| why does minimal change disease happen in children? |
|
Definition
| usually this is idiopathic |
|
|
Term
| are there associations in adults between minimal change disease and other pathologies? |
|
Definition
| yes, there is a strong association w/allergic hx and infection. adults can also present after hodgkin's lymphoma and NSAID therapy. the older pts are when they get this, typically, the worse they do. |
|
|
Term
| how does minimal change disease appear under LM? IF? EM? |
|
Definition
| LM: normal glomeruli, cells of the PCT are filled w/lipids due to reabsorption of lipoproteins (hence the name lipoid necrosis). IF: no staining. EM: diffuse *effacement of foot processes (very important for dx) |
|
|
Term
| what characterizes focal segmental glomerulosclerosis? |
|
Definition
focal: affects <50% of glomeruli
segmental: only a portion of the individual glomeruli are going to be affected |
|
|
Term
| what are some important associations with FSGS? |
|
Definition
| it is seen in HIV and heroin users and is responsible for 10% of nephrotic syndrome in children, and 10-20% of nephrotic syndrome in adults |
|
|
Term
| how quickly can FSGS progress to end stage renal disease? what percent of pts with this die in 10 yrs? |
|
Definition
| FSGS can progress to end stage renal disease within months and 50% will die in 10 yrs |
|
|
Term
| can FSGS be treated with steroids? |
|
Definition
| FSGS is usually steroid resistant |
|
|
Term
| what is seen via LM with FSGS? |
|
Definition
| sclerosis and hyalinosis w/in *some glomeruli. involved glomeruli may contain foam cells. in HIV, the interstitium contains lymphocytes and foam cells. there is also cystic dilation of tubules and bowman's spaces containing proteinaceous material |
|
|
Term
| what is seen via IF in FSGS? |
|
Definition
| mesangial deposits of IgM and C3 in the sclerotic segment of the glomeruli |
|
|
Term
| what is seen via EM in FSGS? |
|
Definition
| diffuse effacement of the foot processes, folding and thickening of the GBM and capillary collapse, focal detachment of epithelial cells w/denudation of underlying GBM |
|
|
Term
| what generally characterizes both kinds of membranoproliferative glomerulonephritis? who is usually affected? how do they present? |
|
Definition
| basement membrane thickening along with endothelial and mesangial cell proliferation. most pts are between 5-30 and present with nephrotic syndrome |
|
|
Term
|
Definition
| a chronic immune complex reaction with glomerular *deposition of circulating complexes - unknown antigen |
|
|
Term
|
Definition
| an infrequent *circulating immune complex, and serum of pts contains *C3 nephritic factor, which can activate the *alternate complement pathway* |
|
|
Term
| how do both type I and II membranoproliferative glomerulonephritis appear via LM? |
|
Definition
| diffuse glomerular enlargement with mesangial hypercellularity, thickened capillary loops, and the capillary wall has a double contour or *tram track* on silver stain |
|
|
Term
| how does membranoproliferative glomerulonephritis type I appear in IF and EM? |
|
Definition
| IF: prominent granular, peripheral deposits of C3, IgG, *C1 and C4* may be present. EM: mesangial cell interposition within the basement membrane, *subendothelial* electron dense deposits are seen |
|
|
Term
| how does membranoproliferative glomerulonephritis type II appear in IF and EM? |
|
Definition
| IF: C3 present in irregular foci in the basement membrane on either side. IgG, C1, C4 are usually absent (b/c it is associated w/the alternate pathway). EM: *dense deposit disease*: ribbon like zone of electron dense material located *centrally in the thickened basement membrane (as opposed to the discrete subendothelial deposits seen in type I) |
|
|
Term
| what is the prognosis for membranoproliferative glomerulonephritis? is one type generally worse? |
|
Definition
| the prognosis for both kinds of membranoproliferative glomerulonephritis is poor, however type II is generally associated with a worse prognosis. recurrent disease in transplanted kidneys is common |
|
|
Term
| what is one of the earliest symptoms of diabetic nephropathy? what associated symptoms usually appear later? |
|
Definition
| proteinuria (if the dr is doing their job), or edema. diabetic nephropathy and HTN usually occur later. |
|
|
Term
| at what point in DM do pts usually start presenting with diabetic nephropathy? |
|
Definition
|
|
Term
| what % of type I & II DM pts does advanced end stage kidney disease occur in? what helps avoid this? |
|
Definition
| 40% strict glucose control helps avoid this outcome |
|
|
Term
| what characterizes advanced end stage kidney disease due to diabetic glomerulosclerosis? |
|
Definition
| non nephrotic range proteinuria and often progression to nephrotic syndrome, and chronic renal failure. also seen are *hyalinized arteriolar sclerosis (microangiopathy) and *papillary necrosis is common. |
|
|
Term
| how does diabetic glomerulosclerosis lead to advanced end stage kidney disease? |
|
Definition
| insulin defect and hyperglycemia lead to *deposition of collagen IV and fibronectin *w/decreased amount of heparin sulfate proteoglycan. nonenzymatic glycation of proteins leads to advanced glycolation end products which "gunk up" the vasculature which leads to hemodynamic changes and glomerular hypertrophy |
|
|
Term
| how are the basement membranes of the nephron affected by diabetic glomerulosclerosis? |
|
Definition
| the capillary and tubular basement membranes thicken |
|
|
Term
| how are the mesangial cells affected by diabetic glomerulosclerosis? |
|
Definition
| there is increased diffuse mesangial sclerosis in the mesangial matrix |
|
|
Term
| what is *nodular glomerulosclerosis*, an effect of diabetic glomerulosclerosis also known as? |
|
Definition
| *kimmelstiel-wilson disease* |
|
|
Term
| what may appear in the periphery of the glomerulus in diabetic glomerulosclerosis? |
|
Definition
| oval nodules may appear in the periphery of the glomerulus in diabetic glomerulosclerosis - visible via LM |
|
|
Term
| how might nodules formed due to diabetic glomerulosclerosis affect the mesangial cells? are all the lonules of the glomerulus usually affected by nodular lesions? |
|
Definition
| the nodules may exhibit mesangiolysis with the formation of capillary microaneurysms. not all the lobules of the glomerulus are affected by nodular lesions, but even uninvolved glomeruli have diffuse *mesangial sclerosis. |
|
|
Term
| what may happen to the renal vasculature in kimmelstiel-wilson disease? |
|
Definition
| the nodules may compress the capillaries, causing the kidneys to become ischemic |
|
|
Term
| what % of long term DM pts develop kimmelstiel-wilson disease? |
|
Definition
|
|
Term
| what is the clinical course of diabetic glomerulosclerosis? tx? |
|
Definition
| increased GFR, microalbuminemia -> proteinuria may progress to nephrotic levels -> progressive loss of GFR -> HTN contributes to renal disease. precise control of blood glucose levels delays or prevents progression of glomerulopathy. |
|
|
Term
| what is acute tubular necrosis often the end product of? |
|
Definition
| ischemia (common, often due to hypovolemic shock, cardiogenic shock, thrombi), direct toxic injury, acute tubulointerstitial nephritis, DIC, and urinary obstruction |
|
|
Term
| what happens to the kidney with acute tubular necrosis? what are the 2 types? |
|
Definition
| destruction of tubular epithelial cells, and acute diminution or loss of renal function. there are 2 types: ischemic and nephrotoxic |
|
|
Term
| are tubular cells sensitive to ischemia, what is the implication of this in terms of the cells specifically? |
|
Definition
| yes, can the tubular cells sensitivity to ischemia can cause reversible or lethal structural changes. there may be depletion of ATP, accumulation of intracellular Ca++, activation of proteases, phospholipases and membrane damage. the cells may also *lose polarity* with redistribution of membrane proteins from basolateral to luminal surface of tubular cells. |
|
|
Term
| what results from the initial ischemic vascular changes to the tubules in acute tubular necrosis? |
|
Definition
| expression of cytokines, detachment of cells resulting in tubule obstruction, increased intratubular pressure and decreased GFR |
|
|
Term
| how is the blood flow affected by acute tubular necrosis? |
|
Definition
| intrarenal vasoconstriction may be due to several vasoconstrictor pathways: increased distal Na+ delivery, and sublethal endothelial injury w/release of *endothelin and decreased production of vasodilators such as *NO and *PGI2 |
|
|
Term
| what is the morphology if ischemic type acute tubular necrosis? |
|
Definition
| focal tubular epithelial necrosis at multiple points along the nephron *w/skipped areas* (not just the PCT). rupture of basement membranes and occlusion of the tubular lumen by *casts. particularly vulnerable are the straight portions of the *PCT and *ascending thick limb in the renal medulla. |
|
|
Term
| in ischemic type acute tubular necrosis, where are eosinophilic casts more common? what are these casts often composed of? where is edema seen? do leukocytes accumulate? |
|
Definition
| in the DCT and collecting ducts, these casts associated with ischemic type acute tubular necrosis are composed of *tamm-horsfall* proteins, hemoglobin and myoglobin. there is often interstitial edema and accumulations of leukocytes. |
|
|
Term
| what is epithelial regeneration seen with ischemic type acute tubular necrosis (seen if the pt survives)? |
|
Definition
| flattened epithelial cells with hyperchromatic nuclei and mitotic figures |
|
|
Term
| what are some of the directions that ischemia in the renal tubules can go? |
|
Definition
| the end result of all forms of ischemia in the renal tubules is reduced GFR and oliguria. this may occur via vasoconstriction (due to increased endothelin, decreased NO/PGI2), and reversible (loss of polarity/detachment/obstruction by casts) or irreversible (necrosis/apoptosis/obsruction of casts/tubular back-leaks) tubular cell injury |
|
|
Term
| where is the injury most obvious in toxic type acute tubular necrosis? |
|
Definition
|
|
Term
| what does mecuric chloride do in toxic type acute tubular necrosis? |
|
Definition
| the injured cells contain large acidophilic inclusions which later *desquamante and calcify |
|
|
Term
| what does carbon tetrachloride do in toxic type acute tubular necrosis? |
|
Definition
| there will be an accumulation of *neutral lipids in injured cells followed by necrosis |
|
|
Term
| what does ethylene glycol (*one of the most common toxins - antifreeze*) do in toxic type acute tubular necrosis? is this kind of injury easily apparent? |
|
Definition
| *balloon and *vacuolarly degenerate the PCT, and form *Ca++ oxalate crystals in the tubular lumens. pts affected by this may have a sweet breath and affected cells scraped off should be identifiable under microscopy. |
|
|
Term
| what are the phases of acute tubular necrosis? what determines the prognosis? |
|
Definition
| initiation, maintenance, and recovery. the prognosis for acute tubular necrosis is dependent on the clinical setting surrounding its development |
|
|
Term
| what is the initiation phase of acute tubular necrosis? |
|
Definition
| slight increase in urine output, slight increase in *BUN |
|
|
Term
| what is the maintenance phase of acute tubular necrosis? |
|
Definition
| sustained decrease in urine output, salt/water overload, rising BUN, *hyperkalemia, and *metabolic acidosis* |
|
|
Term
| what is the recovery phase of acute tubular necrosis? |
|
Definition
| steady increase in urine volume with loss of water, sodium and potassium - causing hypokalemia |
|
|
Term
| what is acute pyelonephritis? |
|
Definition
| infection of the kidneys, often shared with the bladder |
|
|
Term
| what are clinical presentations of pts with acute pyelonephritis? |
|
Definition
| flank pain (gibbs punch), fever, malaise, dysuria (like "peeing battery acid"), and pyuria |
|
|
Term
| what are common ways for acute pyelonephritis to spread? |
|
Definition
common: ascending infection (instrumentation (catheters) in females will commonly cause this, also kidney stones, paralysis or congenital defects), also:
septicemia or endocarditis. |
|
|
Term
| what kind of bacteria are commonly seen in acute pyelonephritis due to ascending infections? |
|
Definition
| gram negative, specifically e coli |
|
|
Term
| what is the vesicoureteral reflex? |
|
Definition
| reflux of urine and bacteria |
|
|
Term
| how does acute pyelonephritis affect the kidney? |
|
Definition
| there may be *discrete yellow abscesses on the renal surface, *papillary necrosis (on apical 2/3 of pyramids), and acute cystitis (aka bladder involvement) |
|
|
Term
| what can cause chronic obstructive pyelonephritis? is it usually uni- or bilateral? can anomalies of the urethra or calculi cause this? |
|
Definition
| recurrent bouts of renal inflammation and scarring. chronic obstructive pyelonephrotis may be due to anomalies of the urethra or calculi |
|
|
Term
| what does pyelonephritis generally refer to? what is "reflux nephropathy"? |
|
Definition
| pyelonephritis generally refers to renal inflammation. reflux nephropathy generally refers to reflux of urine into the kidney due to obstruction, therefore *it is another name for chronic obstructive pyelonephritis |
|
|
Term
| what is the morphology (grossly/microscopically) of chronic obstructive pyelonephritis? how are the glomeruli affected? |
|
Definition
| grossly: uneven subcapsular scarring involving the pelvis, calyces or both. papillary blunting, microscopically: chronic inflammatory infiltration - though the glomeruli are usually normal (at least early on). |
|
|
Term
| what is the clinical course for chronic obstructive pyelonephritis? |
|
Definition
| gradual onset of renal insufficiency, HTN, abnormal lab tests. some pts eventually develop glomerular lesions. |
|
|
Term
| what drugs can cause acute drug induced interstitial nephritis? |
|
Definition
| synthetic PCNs, diuretics, and NSAIDs |
|
|
Term
| what are clinical symptoms of acute drug induced interstitial nephritis? |
|
Definition
| fever, eosinophilia (always think of this w/drugs), skin rash, hematuria, proteinuria, and leukocyturia |
|
|
Term
| what % of pts with acute drug induced interstitial nephritis progress to acute renal failure? |
|
Definition
|
|
Term
| what does withdraw from the causative drug usually lead to in acute drug induced interstitial nephritis? |
|
Definition
|
|
Term
| what is benign nephrosclerosis? how does it appear? how does it affect the kidney? |
|
Definition
| renal changes due to benign HTN (usually idiopathic). benign nephrosclerosis appears as hyaline arteriosclerosis (homogenous pink thickening of the vessel) and granular cortical surface (lots of little white dots), and focal tubular atrophy. these usually result in decreased blood flow. |
|
|
Term
| what is malignant nephrosclerosis? how does it appear? how does it affect the kidney? |
|
Definition
| renal changes due to malignant HTN. this results in *fibrinoid necrosis of arterioles w/inflammatory infiltrates in the vessel well as well as intimal thickening by *proliferation of concentric smooth muscle (onion skinning) |
|
|
Term
| are simple cysts a common finding in the kidneys? where in the kidney are they usually found? size? |
|
Definition
| yes, and they are usually found in the cortex (single/multiple) and can be 1-5 cm in diameter |
|
|
Term
| what is adult polycystic kidney disease? how is it acquired? what is the specific cause? |
|
Definition
| multiple expanding cysts of both kidneys that destroy the renal parenchyma. it is inherited autosomally dominantly is due to a defective polycystin protein |
|
|
Term
| when do pts w/adult polycystic kidney disease usually present w/symptoms? how do they present? can it result in renal failure? |
|
Definition
| pts with adult polycystic kidney disease usually present with flank pain, intermittent hematuria, HTN, UTIs, *berry aneurysms* (in anterior circle of willis in which subsequent rupture may lead to subarachnoid hemorrhages and death), and *liver cysts in their 30s. ultimately adult polycystic kidney disease can develop into chronic renal failure. |
|
|
Term
| how do cysts form in adult polycystic kidney disease? |
|
Definition
| mutations in polycystin 1,2 lead to defects in cell-cell/cell-matrix interations, leading to altered tubular epithelial growth and differentiation - which then leads to: abnormal ECM, cell proliferation, and fluid secretion |
|
|
Term
| what is the main problem with adult polycystic kidney disease? |
|
Definition
| the sheer number - which is why this disease is much worse than simple cysts |
|
|
Term
| what is childhood polycystic kidney disease? what pathologies are associated with it? |
|
Definition
| this is an autosomally recessive disease resulting in numerous small cysts in a younger age group. associated with it are numerous liver cysts and proliferation of *portal bile ducts and *hepatic fibrosis |
|
|
