Term
| describe the glomerulus in terms of composition |
|
Definition
| the glomerulus is a capillary, 1 cell layer thick. it has an endothelium, BM, and epithelium. the BM has 3 layers (lamina rara interna/lamina densa/lamina rara externa). it is covered on both sides by sialoproteins |
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|
Term
| what gives the glomerular BM its negative charge? what is the purpose of this? |
|
Definition
| the sialoprotein - which provides a negative charge, repelling other negatively charged proteins such as albumin |
|
|
Term
| what is the gradient of albumin that gets through the GBM? what controls this? |
|
Definition
| 10,000:1, so if normal albumin levels are 4g/dL, then .4mg/dL albumin will cross the barrier. *this is accomplished via the negative electric charge* |
|
|
Term
| how much albumin is filtered per day? what % of this filtered albumin is reabsorbed? |
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Definition
| 720 mg is filtered a day, of which, 95-98% is reabsorbed, leaving 20-30 mg/day in the urine under normal circumstances |
|
|
Term
| what is the max level of total protein per day that can be found in the urine? what makes up most of this protein? how much of it is albumin? beta 2 microglobulin? |
|
Definition
| up to 150 mg/day - most of which is the *tamm horsfall glycoproteins* 20-30 mg is albumin and 5 mg is beta 2 microglobulin. |
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|
Term
| are tamm horsfall proteins found in the blood? |
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Definition
| no, they are only found in the kidney and produced by the renal tubule epithelial cells. it is the protein that makes up the matrix of casts (normal casts are hyaline) |
|
|
Term
| what is transient proteinuria? |
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Definition
| a functional intermittent proteinuria that is usually acute or self-limiting, seen after fever or exercise |
|
|
Term
| what is orthostatic proteinuria? |
|
Definition
| a benign condition that describes itself. this can be tested for by doing a day and night collection. the night collection would not have protein in it |
|
|
Term
| what does persistant proteinuria represent? |
|
Definition
| this is abnormal and represents disease |
|
|
Term
| what are different things that can cause glomerular proteinuria? |
|
Definition
| a defect in size of the selective barrier, a defect in the selective charge of the barrier, and a defect in renal hemodynamics (functional proteinuria) |
|
|
Term
| what is associated with tubular proteinuria? |
|
Definition
| beta 2 microglobulin, b/c it is freely filtered and the only reason it would show up in the urine is if the tubules are not reabsorbing it |
|
|
Term
| what is overflow proteinuria? |
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Definition
| nothing wrong with the kidney, there is too much of something in the blood (light chain overproduction (multiple myeloma), myoglobinuria, hemoglobinuria) |
|
|
Term
| what is clinical albuminuria? |
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Definition
| albumin levels high enough to be picked up on a dipstick (>300 mg/day or macroalbuminuria) - a definite indication of a glomerular problem |
|
|
Term
| how is microalbuminuria detected? what is considered clinical microalbuminuria? |
|
Definition
| not by dipstick, but there is a specific stick for it. clinical microalbuminuria is considered 30-300 mg/day |
|
|
Term
| what are normal and clinical proteinurias? |
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Definition
| normal is 150 mg/dL or less/day. clinical proteinuria is >500 mg/day (300 of this is albumin, the rest is normal stuff). remember this is different than 'albuminuria' |
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|
Term
| how is a 24 urine collection done? how do you make sure the pt did it correctly? |
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Definition
| 24 hrs, the pt pees in a jug. you have to tell the lab to record creatinine levels, and a serum creatinine (separate test) which you can then use determine if the pt did indeed pee in the jug for 24 hrs. |
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|
Term
| how much creatinine do males excrete per day? women? how can this be used to calculate level of proteinuria? (*know this*) |
|
Definition
| males excrete 20-25 mg/kg/day creatinine in urine. females exrete 15-20 mg/kg/day creatinine in urine. you can use this to find out how much creatinine a pt of a specific weight excretes per day (ie 70 kg male excretes 1.4 gm/day creatinine) and multiply this times the PCR (protein creatinine ratio) found from a random urine sample (ie 1000 mg protein/g creatinine) and get 1400 mg protein/day (or 1.4 g) |
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|
Term
| what are mild/moderate/severe amounts of protein to be found in the urine? |
|
Definition
mild: <1 g/day
moderate: 1-3.5 g/day
severe (nephrotic): >3/5g/day |
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|
Term
| what kind of electrophoresis spike will be seen in a pt with multiple myeloma? |
|
Definition
| gamma spike (tamm horsfall would show in this region) |
|
|
Term
| what is an SSA? when would you use it? |
|
Definition
| SSA: sulfa salicylic acid test, which tests for all types of protein, including but not limited to albumin. therefore if you have a negative dipstick but a positive SSA, you might have a tubular proteinuria, which is marked by a preponderance of beta 2 microglobulin. this helps the dr do a more thorough screening w/out immediate need for electrophoresis |
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|
Term
| what is the quick and dirty definition of azotemia? |
|
Definition
| some elevated creatinine and/or BUN |
|
|
Term
| what is the approach to pts with azotemia? |
|
Definition
| via H+P/blood work/urine tests/radiography, you land at either: pre-renal, renal parenchymal (either glomerular, tubulo-interstitial, or vascular), or post-renal |
|
|
Term
| what are the five major syndromes of glomerular disease? |
|
Definition
| nephrotic syndrome, acute glomerulonephritis, chronic glomerulonephritis, rapidly progressive glomerulonephritis (RPGN), or "asymptomatic" hematuria and/or proteinuria (dx of exclusion) |
|
|
Term
| what is nephrotic syndrome generally? |
|
Definition
| a constellation of clinical and laboratory abnormalities occurring as a result of increased permeability of the glomerular capillary wall to plasma proteins |
|
|
Term
| what is nephrotic syndrome clinically? |
|
Definition
| proteinuria >3.5 g/day, hypoalbuminemia, edema (dependent (gravity) or anasarca (severe/entirebody)), hyperlipidemia (maltese cross), and hypercoagulable state |
|
|
Term
| where is a good place to look for edema on pts suspected of nephrotic syndrome? |
|
Definition
| the sacral bone, which should make an indentation w/pressure |
|
|
Term
| what is a fatty cast? what is it indicative of? |
|
Definition
| a fatty cast is indicative of nephrotic syndrome (hyperlipidemia) and is a normal hyaline cast with lots of round blobs of differing sizes in it |
|
|
Term
| what is the maltese cross associated with nephrotic syndrome? |
|
Definition
| the fat droplets in fatty casts may have a cross-like appearance under polarized light |
|
|
Term
| how does nephrotic syndrome lead to a hyperlipidemic state? |
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Definition
| the loss of protein in the urine causes a compensatory response by the liver to produce more protein (specifically a lot of albumin). the protein producing pathway is linked to the lipid producing pathway, which the liver will increase along with protein production. |
|
|
Term
| how does nephrotic syndrome lead to a hypercoagulable state? |
|
Definition
| anticoagulant proteins such as anticoagulant III are lost in the urine, and more clotting factors are produced |
|
|
Term
| what are complications of nephrotic syndrome? |
|
Definition
| acute renal failure, thrombo-embolic events, accelerated arteriosclerosis, anemia, immunodeficient state, hypocalcemia, and other protein losses |
|
|
Term
| how can nephrotic syndrome lead to acute renal failure? |
|
Definition
| there is a tendency to administer diuretics for edema, but it can lead to pre-renal azotemia, then acute renal failure which can cause hypotensive shock and acute tubular necrosis |
|
|
Term
| how can nephrotic syndrome lead to thrombo-embolic events? |
|
Definition
| DVT, renal vein thrombosis, and PEs all may occur due to hypercoagulable state. (there are only two situations where you get renal vein thrombosis: nephrotic syndrome and trauma) |
|
|
Term
| how can nephrotic syndrome lead to accelerated arteriosclerosis? |
|
Definition
| this is due to hyperlipidemia |
|
|
Term
| how can nephrotic syndrome lead to anemia? |
|
Definition
| amemia can occur due to loss of transferrin (lose Fe) and erythropoietin |
|
|
Term
| how can nephrotic syndrome lead to immunodeficiency? |
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Definition
| immunodeficiency due to loss of Igs and complement components |
|
|
Term
| how can nephrotic syndrome lead to hypocalcemia? |
|
Definition
| albumin carries Ca++, so both are lost in nephrotic syndrome. vit D carrying proteins are also lost in urine (sets you up for secondary hyperparathyroidism) |
|
|
Term
| what are other protein losses due to nephrotic syndrome? |
|
Definition
| a lot of endocrine carrying proteins are lost including thyroxine and corticosteroids |
|
|
Term
| why is proteinuria an important risk factor for progressive renal demise? |
|
Definition
| increased *mesangial traffic, *tubulotoxicity (scarring/inflammation from overworked reabsorption effort) |
|
|
Term
| what are components of the mesangial zone vulnerable to damage via proteinuria? |
|
Definition
| damage to the mesangial zone and its functions (such as neuro-sympathetic innervation) can affect contraction of the afferent arteriole, controlling pressure of the capillary; endocrine receptors and growth factors are produced here |
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|
Term
| what is the effect of proteinuria on loss of GFR? |
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Definition
| parabolic, the more protein you lose, the more GFR you are going to lose as a result |
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|
Term
| what do you do to tx nephrotic syndrome irrespective of its cause? other types of management? |
|
Definition
| irrespective of cause: water and Na+ restriction. diuretics are used judiciously. local care/anti-gravity measures (leg elevation/wrapping). modest protein restriction (.8 g/kg/day). standard rx therapy: ACE inhibitors, ARBs, diltiazem (not verapamil or nifedipine). anti-platelet/anti-coag if thrombus somewhere. vitamins/minerals if deficient. |
|
|
Term
| what are 3 important histologic lesions that can cause nephrotic syndrome? |
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Definition
| minimal change disease, membranous glomerulopathy, and focal & segmental glomerulosclerosis |
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|
Term
| what are 2 other names given to minimal change disease? |
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Definition
| lipoid nephrosis and nil’s disease |
|
|
Term
| what is the etiology of minimal change disease? |
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Definition
| idiopathic or secondary to systemic disease (lymphomatous: hodgkins or non-hodgkins, occasionally renal cell cancer and other solid tumor disorders). it is sometimes associated with atopic individuals |
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|
Term
| how does minimal change disease present clinically? |
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Definition
| nephrotic syndrome without hematuria. normal renal function. normal complement levels. normal BP. it may follow a URI or prophylactic immunizations. |
|
|
Term
| who does minimal change disease occur in most often? |
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Definition
|
|
Term
| what is the pathology of minimal change disease? |
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Definition
| it is related to the lymph cell line (not clearly understood) secreting factors that affect the epithelial cell. this is based on its association with infections/immunizations/atopy/lymphoproliferative disease AND response to steroids |
|
|
Term
| how does minimal change disease appear on EM? |
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Definition
| the foot process are fused = hallmark of minimal change disease. it seems counterintuitive that fusion of cells causes more protein to leak out, but keep in mind that the leakage is more due to loss of *electronegative charge*, and fusing of the foot processes may be a simple compensatory response trying to hold the protein in |
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|
Term
| who recovers better from tx of minimal change disease? |
|
Definition
|
|
Term
| what are common causes of membranous glomerulopathy? |
|
Definition
| idiopathic or secondary by: infection (hep b,c, syphilis, leprosy, parasitic), multisystem (SLE, mixed connective tissue disease, RA, sjrogren's, sarcoidosis), neoplasia (carcinoma, lymphoma, leukemia - reverse of minimal change, test for CA in adults), medications (organic gold, mercury, D-penicillamine, captopril), and misc (sicke cell, thyroiditis, chronic allograft rejection, fanconi syndrome) |
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|
Term
| what is the clinical course/features of membranous glomeruolopathy? |
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Definition
| there is an insidious onset of nephrotic syndrome, occasional microhematuria, and spontaneous remission of 10-25% over 3-4 yrs. it can progress to anasarca/dropping albumin |
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|
Term
| what are risk factors for progression of membranous glomerulopathy? |
|
Definition
| male, persistant massive nephrosis, HTN, renal insufficiency |
|
|
Term
| what happens to the BM in membranous glomerulopathy? |
|
Definition
| there are deposits of immune material on the epithelial side, and where this happens, foot processes begin to fuse. eventually this surrounds the entire membrane and it shoots fingerlike projections in between the immune deposits in an attempt to engulf them. once engulfed, the deposits cannot be seen anymore, but the membrane is extremely distorted and loses its integrity/charge. |
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Term
| what does IF show with membranous glomerulopathy? |
|
Definition
| continuous (not patchy) fluorescently tagged Igs and NOT in the mesangial zone |
|
|
Term
| what is the most common histologic finding for all bxs found due to nephrotic syndrome? |
|
Definition
| focal segmental glomerulosclerosis |
|
|
Term
| who does focal segmental glomerulosclerosis affect more as an idiopathic lesion? |
|
Definition
|
|
Term
| what does the histologic description of focal segmental glomerulosclerosis represent? |
|
Definition
| the final common pathway of all chronic renal/glomerular disease (b/c we're dealing with sclerosis) |
|
|
Term
| what causes focal segmental glomerulosclerosis? |
|
Definition
| idiopathic or secondary, important examples of which are morbid obesity, HIV (main renal lesion associated w/this), heroin, and all situations of reduced renal mass (reflux nephropathy, post nephrectomy, and congenital solitary kidney) |
|
|
Term
| how does focal segmental glomerulosclerosis present as a primary disease? what is its progression? how is it treated? |
|
Definition
| HTN, azotemia, some degree of microhematuria. it may progress to ESRD in 6-8 yrs. steroids may help in long doses. |
|
|
Term
| is there any specific therapy for HIV FSGS? |
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Definition
| no, other than HAART and the fact that ACEI/ARBs slows progression to ESRD |
|
|
Term
| when does the macrovascular disease associated with DM set in? what organs does it affect? what does the microvascular disease affect? |
|
Definition
| macrovascular disease (atherosclerosis) can set in before blood sugar is elevated and affects the brain, heart and lungs. microvascular disease (arteriolosclerosis) can cause retinopathy, neuropathy, and nephropathy |
|
|
Term
| what is the most common cause of ESRD in the US? |
|
Definition
|
|
Term
| what is stage I (0-2 yrs) of renal disease in DM type I pts? |
|
Definition
| functional changes, featuring increased GFR, reversible albuminemia, increased kidney size (high serum glucose expands the volume of the serum and thus the volume of the kidney) |
|
|
Term
| what is stage II (2-3 yrs) of renal disease in DM type I pts? |
|
Definition
| structural changes, featuring GBM thickening, mesangial expansion, (both are cellular matrix expansions) |
|
|
Term
| what is stage III (3/7-10/30 yrs) of renal disease in DM type I pts? |
|
Definition
| incipent nephropathy, featuring hyperfiltration (150), microalbuminuria, HTN, and poor glycemic control - start treating with ACEIs and ARBs (even if not HTNsive) |
|
|
Term
| what is stage IV (10/30-15/40 yrs) of renal disease in DM type I pts? |
|
Definition
| clinical nephropathy, featuring proteinuria detectable via dipstick, rising creatinine, edema |
|
|
Term
| what is stage V (15-40) of renal disease in DM type I pts? |
|
Definition
| ESRD - dialysis dependent |
|
|
Term
| how is diabetic nephropathy diagnosed? |
|
Definition
| appropriate clinical hx, diabetic retinopathy, proteinuria, and relatively large kidney size (preserved ECHO texture - distinction between cortex and medulla) -> have to have DM long enough to see these changes |
|
|
Term
| how is kidney size affected by DM vs other disease? ECHO texture (distinction between cortex and medulla)? |
|
Definition
| normal kidney size is 10-12 cm. kidney disease of any other type (ie HTN) than DM will cause the kidney to shrink, but a diabetic kidney starts out big and then shrinks to normal size. similarly ECHO texture is disrupted in any other kidney disorder besides DM |
|
|
Term
| when microalbuminuria (30-300 mg/day) is seen in DM pts, what needs to happen? |
|
Definition
|
|
Term
| can glucose control reduce risk of microvascular disease? |
|
Definition
|
|
Term
| what are the two categories of diabetic retinopathy? |
|
Definition
| background and proliferative. proliferative will cause eyesight loss (treatable w/lazer). |
|
|
Term
| what DM-related kidney pathology is always on boards? |
|
Definition
| the kimmelstiel-wilson kidney, featuring nodular glomerular sclerosis |
|
|
Term
| what is the most common diabetic nephropathy? |
|
Definition
| diffuse glomerular sclerosis |
|
|
Term
| what are the rough 20 yr changes in DM that lead to kidney disease in pts? |
|
Definition
| age 20: insulin resistance increases, insulin levels go up to compensate. dyslipidemia also occurs. age 40: pancreas begins to wear out, insulin levels drop, resistance continues to rise. age 60: insulin falls, frank hyperglycemia - this is when DM diagnosis is made, and vascular disease has already taken place |
|
|
Term
| how is diabetic nephropathy managed? |
|
Definition
| glucose control, ACEIs/ARBs to reduce proteinuria to <500 mg/day, dietary protein restriction, manage lipid disorder, smoking cessation |
|
|
Term
| what characterizes acute glomerulonephritis? |
|
Definition
| it is acute, most commonly due to infection - prototype being post-streptococcal glomerulonephritis |
|
|
Term
| what characterizes chronic glomerulonephritis? |
|
Definition
| starts idiopathically, progresses slowly until they show up on a urine test - HTN may be involved and creatinine may rise over time |
|
|
Term
| what is the hallmark of RPGN? |
|
Definition
| rapidly progressive glomerulonephritis is marked by crescents and is acute by definition and leads to ESRD |
|
|
Term
| what defines nephritic syndrome? |
|
Definition
| edema (not b/c of albumin, but filtering units are being destroyed), proteinuria+hematuria (not just leaky, glomerulus is being destroyed), HTN (due to volume expansion and loss of mesangial regulation), and +/- acute renal failure |
|
|
Term
| what are mediators of immunologic renal injury? |
|
Definition
| soluble: complement components, fibrinogen, prostacycline/thromboxanes, leukotrienes, kinins, histamine, angiontensin II and cellular:PMNs, mononuclear, platelets, and lymphocytes |
|
|
Term
| what happens in immunologic renal injury? |
|
Definition
| antigen excess, due to not being taken out (due to size, should be removed by the spleen/liver) and end up in microcirculation - they can get under a podocyte and cause immunologic problems |
|
|
Term
| what is the pathogenesis of immunologic renal injury? |
|
Definition
| there are circulating immune complexes or circulating antibody to native/planted antigen that then cause immune rxns w/in the glomerulus, activate mediators of injury, and cause glomerular injury/scarring |
|
|
Term
| how does immunologic renal injury present clinically? |
|
Definition
| hematuria, proteinuria, azotemia, and HTN |
|
|
Term
| what is an RBC cast a hallmark of? |
|
Definition
|
|
Term
| how do glomeruli look after being affected by post-streptococcal nephritis? |
|
Definition
|
|
Term
| how do kids vs adults fare with post-streptococcal GN? |
|
Definition
|
|
Term
| how long after the sore throat does post-streptococcal GN manifest itself? |
|
Definition
|
|
Term
| is mesangial proliferative GN acute or chronic? |
|
Definition
|
|
Term
| what is the most common form of mesangial proliferative GN? |
|
Definition
| most common: predominant IgA mesangial deposits - berger's disease |
|
|
Term
| what is the prognosis for IgA nephropathy (mesangial proliferative GN)? |
|
Definition
|
|
Term
| how quickly can RPGN progress to ESRD if left untreated? |
|
Definition
|
|
Term
| what is the hallmark of RPGN? what is the cell that proliferates? |
|
Definition
| crescents. visceral epithelial cells do the proliferating |
|
|
Term
| what is the most common type of RPGN? |
|
Definition
| goodpastures - antiGBM, also affects the lungs. also can be just antiGBM |
|
|
Term
| what is one of the few GN's that might be successfully treated? |
|
Definition
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