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111 Cards in this Set
- Front
- Back
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What is azotemia?
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Azotemia is the elevation of BUN and creatinine- due largely to a decreased GFR.
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Describe the 3 different types of azotemia.
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1. Pre-renal- occurs when there is hypoperfusion of the kidney ie hemorrhagic shock, volume depleteion ect
2. Renal- Intrinsic disease of the kidney ie ATN, toxins 3. Post renal- occurs whenever urine outflow is obstructed ie prostate enlargement, stones ect |
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What is uremia?
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Uremia is azotemia ( the elevation of BUN and creatinine) associated with a constellation of signs and symptoms seen in many organ disease. Ex of these symptoms are hypothermia, glucose intolerence, elevated TAGs ect. This is a hallmark of chronic renal failure.
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What is acute renal failure?
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Acute renal failure is the deterioration of renal function over a period of hours to days reulting in failure of the kidney to excrete nitrogenous waste and to maintain fluid and electrolyte homeostasis. Usually reversible.
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What are some of the causes of acute renal failure?
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Acute renal failure can result from glomerular, interstitial, vascular injury or acute tubular necrosis.
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What is chronic renal failure?
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Chronic renal failure is the progressive destruction of the nephron mass, characterized by prolonged sighns and ymptoms of uremia. It is the end result of all renal disease.
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What is the most common cause of chronic renal failure?What are some other common causes?
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The most common cause of chronic renal failre is glomerulonephritis. Other causes are DM, polycystic kidney disease, nephrosclerosis, ect
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What are the stages of chronic renal failure?
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1. Diminished renal reserve
2. Renal insufficiency 3.Overt renal failure 4. End Stage renal disease |
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Describe diminished renal reserve.
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Diminished renal reserve= GFR=35-50%, BUN normal and pt is asymptomatic
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Describe renal insufficiency.
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GFR= 20-35%, azotemia, uremia, anemia, HTN, polyuria, nocturia
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Describe overt renal failure
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GFR= 25-20%, edema, metabolic acidosis, hypocalcemia
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Describe end stage renal disease
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GFR<5%, terminal stage of uremia
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What are the four basic morphological components that kidney disease can be divided into.
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Glomeruli, Tubules, Intersitium, Blood Vessels All of these can be primary or secondary. Keep in mind that damage to one of these components almost always secondarily affects the other,
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What is the difference between primary and secondary glomerular disease.
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Primary glomerular disease occurs when the the glomerulus is the site of origin of the disease while secondary glomerular disease occurs when the glomeruli is affected by a systemic disease process
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Is primary glomerular disease associated with nephritic or nephrotic syndrome
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Nephrotic Syndrome
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What is the primary mechanism underlying most cases of primary glomerulonephritis?
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Immune mechanisms
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Define nephrotic syndrome.
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Nephrotic syndrome- massive proteinuria ( >3.5 g/24hr), hypoalbuminemia, generalized edema, hyperlipidemia and lipiduria ( oval fat bodies in the urine). Also may have increased vulnerability to infections to staphylococi and pneumococci and thrombolitic and thromboembolic complications.
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Define nephritic syndrome.
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Hematuria ( RBCs and RBC casts), oliguria ( rarely anuria), azotemia, HTN( classically tranisient), some proteinuria and slight edema
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What is the most common cause of nephrotic syndrome in children?
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The most common cause of nephrotic syndrome in children is Minimal Change disease aka lipiod nephrosis. It represents 65% of nephrotic children and 10% of nephrotic adults.
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What are the clinical manifestations of Minimal Change Disease?
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It can follow a respiratory infection or vaccination in children (sometimes adults). Presents with normal renal function, no HTN or hematuria. Highly selective proteinuria- albumin.
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What is the proteinuria in Minimal Change disease?
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Albumin
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What is the outcome in Minimal Change disease?
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Remitting and relapsing course, dramatically steroid responsive, overall good prognosis.
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What is the light microscope pathology of minimal change disease?
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Normal glomeruli, tubointerstitium and blood vessels. Proximal tubules may contain lipid- reflecting the tubular reabsorption of lipids through the diseased glomeruli
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What is the electron microscope pathology of minimal change disease?
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Uniform and diffuse loss of foot processes of the visceral epithelial cell cytoplasm and villous hyperplasia. No granular electron dense deposits,
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What is the IF result in minimal change disease?
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Negative, there are no Ig or complement deposits
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Is focal segmental glomerulosclerosis primary or secondary?
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Both. Focal segmental glomerulosclerosis idiopathic in 10-15% of cases. It can also be seondary to HIV, heroin, glomerular scarring, an adaptive response in glomerular ablation nephropathy or be in certain inherited forms of nephrotic syndrome.
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What is the most common nephrotic syndrome in US adults?
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Focal Segmental glomerulosclerosis
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What races are more prone to develop Focal Segmental Glomerulosclerosis?
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Blacks and Hispanics
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Focal Segmental glomerulosclerosis may have a shared spectrum with what other disease?
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MCD. FSGS patients have a nonselective proteinuria, more likely hematuria, reduced GFR, HTN and a poor response to steroids. It may be the poor end of the MCD spectrum
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What is the primary glomerular lesion in all cases in idiopathic focal segmental glomerulosclerosis?
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Visceral epithelial damage ( effacement or detachment) in affected glomerular segements
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Describe the symptoms of focal segmental glomerulosclerosis.
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The nephrosis is steroid dependent or steroid resistant ( especially poor response in idiopathic cases). Associated iwth HTN and hematuria. Course generally associated with eventual progression to end stage disease. May reoccur in allografts. Proteinura occurs rapidly after transplants.
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Describe the light microscopic pathology of FSGS.
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Characterized by the sclerosis of some( not all hence focal) glomeruli and in the affected glomeruli only a portion of the capillary tuft is involved( hence segmental). Tends to be involved in the juxtamedullary glomeruli. In sclerotic segements, there is collapse of BM, increase in matrix and deposition of hyaline masses ( hyalinosis), oten with lipid droplets and foam cells. Normal glomeruli may be normal or show increased mesangial matrix and proliferation . Often pronounced hyaline thickening of afferent arterioles.
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Where does FSGS often intially involve.
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The juxtameduallary glomeruli
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What are the results of IF in FSGS.
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There are IgM and C3 present within the hyaline masses in sclerotic areas
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What are the EM results of FSGS.
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Both sclerotic and non sclerotic areas show diffuse loss if foot processes and there is focal detachement of the epitheilial cells with denudation of the underlying GBM.
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What is the key feature in distinguishing betweem FSGS and MCD
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Both have diffuse loss of the foot processes, but in FSGS there is pronounced, focal detachment of the epithelial cells with denudation of underlying GBM
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What are the two histological variants of FSGS and what is their prognostic indication.
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1. Tip lesion only- good
2.Collapsing variant- very bad. Collapsing variant can be idiopathic, but it is also a characteristic pathological finding in HIV. The HIV nephropathy also demonstates sclerosis of the entire glomerulus in addition to endothelial tubuloreticular inclusions on EM. Best prognostic indicator is the extent of sclerosis |
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Describe the HIV variant of FSGS
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The HIV nephropathy also demonstates sclerosis of the entire glomerulus in addition to endothelial tubuloreticular inclusions on EM
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What is the clinical manifestation and course of FSGS
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Children have better prognosis. Little spontanous remission. Responses to corticosteroid are variable. ~ 20% follow rapid course leading to renal failure within 2 yrs
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What is the most common cause of nephrotic syndrome in adults?
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Membranous Glomerulonephritis
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Is membranous glomerulonephrtis primary, secondary or both?
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Both. It is primary in 85% in the cases and 15% secondary.
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When do you see secondary membranous glomerulonephritis?
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Secondary membranous glomerulonephritis is seen on certain drugs( penicillamine, captopril), underlying malignant tumors, SLE, infections and metabolic drugs
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What causes membranous glomerulonephritis?
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Immunologically mediated glomerular injury via immune complexes that accumulate on the subepithelial side of the BM. There is no cellular proliferative or inflammatory response. In secondary, specific antigens can sometimes be implicated
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What is the LM pathology of membranous glomerulonephritis?
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Normal in the early dz. Uniform, diffuse thickening of the glomerular capillary wall with or w/o spikes on special stains. The spikes represent BM material laid down btwn dense deposits. As the disease progresses , glomeruli become totally sclerotic or hyalinized.
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What is the IF result in membranous glomerulopathy?
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Positive for granular deposits of IgG and sometimes C3 along GBM, sparing the mesangium.
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What is the EM appearance of membranous glomerulopathy?
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Dense deposits located btwn GBM and epithelial cell(subepitheial), BM material is laid down btwn these deposits producing characteristic " spikes", best seen with silver stains. Epithelial cells lose foot processes.
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What are the clinical manifestations of membranous glomerulonephritis?
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Typically insidious onset, usually indolent course. Non-selective proteinuria with poor response to steroids. Progression associated with increased glomerular sclerosis, increased BUN, decreased proteinuria severity and increased HTN. Women and children have better prognosis. Only 10% die or progress to renal failure. 40% progress to renal insufficiency. Some sponatanous remission
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IS membranoproliferative glomerulonephritis primary, secondary or both?
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Both. There are two types of primary ( type 1 and 2) and MPGN can be secondary.
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What are some of the causes of secondary MPGN?
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It can be secondary to chronic immune complex disease, partial lipodystrophy, alpha 1 anti-trypsin deficiency, malignant diseases or hereditary complement deficiency.
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What type of primary MPGN is more common?
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Type 1 makes up the majority of cases
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Describe the mechanism of type 1 MPGN.
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There is the deposition of subendothelial and mesangial immune complexes with activation of the classical and alternative pathways. These complexes incite a proliferative/inflammatory response.
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Describe the mechanism of type 2 MPGN
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This involves the activation of the alternative complement pathway. There is a decreased level of factor B and properidin. 70% of pts have a circulating antibody( C3 nephritic factor/ C3NeF). C3NeF is an autoantibody that binds to the alternative pathway C3 convertase and stabilizes it therefore protecting it from degradation. This causes there to be persistent C3 degradation and hypocomplementemia. Note that C1 and C4 levels are normal.
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Describe the light microscope apperance of MPGN type 1 and 2.
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They appear similar. There are large, hypercellular glomeruli with a "lobular" apperance. The hypercellularity is produced by increased numbers of mesangial cells as well as infiltrating leukocytes and parietal epithelial cells. The GBM is thickened. Duplication of the BM="tram track which is best seen on special stains. In type 2, intramembranous ribbon-like deposits can sometomes be seen.
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Describe the EM of MPGN type 1 and 2.
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Type1- subendothelial deposits
Type 2- dense homogenous deposits in the lamina densa hence "dense deposit disease" |
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What are the IF results of type 1 and 2 MPGN.
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Type 1- coarse, granular C3, sometimes C1q and C4 along capillary loops
Type 2- Irregular granular or linear foci of C3 in BM and mesangium, but not within dense deposits. |
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What are the clinical manifestations of MPGN.
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Seen in older children/young adults. Nephrotic range proteinuria with a nephritic component ( hematuria). Slowly progressive. 50% develop chronic renal failure. Persistently low C3
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Is secondary MPGN classified as type 1 or 2.
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Type 1.
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What are the two main categories of nephritic syndrome?
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1. Acute proliferative glomerulonephritis (poststreptococcal/postinfectious)
2. Rapidly progressive( crescentic) glomerulonephritis |
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What is Acute Glomerulonephritis? acute Nephritic Syndrome and how does it present?
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It is and inflammatory alteration in the glomeruli. Clinically, pts usually present with hematuria, red cell casts, azotemia, oliguria and mild to moderate HTN.
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Who is affected by Acute Proliferative Glomerulonephritis?
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Children 6-10 who have had a group A beta-hemolytic streptococcal infection of the pharynx or the skin 1-4 wks prior.
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What is the LM appearance of Acute Proliferative Glomerulonephritis?
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Diffuse( therefore all) glomerular hypercellularity due to infiltration by neutrophils and monocytes, proliferation of endothelial and mesangial cells and in more severe cases crescent formation. This causes obliteration of the capillary lumens. Also there is typically fibrin deposits in capillary lumens and measangium, interstial edema and inflammation and red cell cast in tubules
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What causes the hypercellularity in Acute proliferative glomerulonephritis?
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Infiltration by neutrophils and monocytes, proliferation of endothelial and mesangial cells and in more severe cases crescent formation
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What are the IF results in Acute Proliferative glomerulonephritis?
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Focal granular deposits of IgG, IgM and C3 in the measngium and along the BM
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What is the EM appearence of Acute Proliferative Glomerulonephritis?
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Subepithelial humps made up of discrete, amorphous electron-dense deposits on epithelial side of GBM. THese represent antigen-antibody complexes.
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What are the clinical manifestations of Acute Proliferative Glomerulonephritis?
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A child who develops malaise, fever, nausea, olguria and hematuria 1-2 wks after sore throat. Urine will contain RBC and RBC casts and small amount of protein, Child can have peri-orbital edema and HTN. >95 % recover.
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What are the lab results of Acute Proliferative Glomerulonephritis?
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Elevated ASO titers, decreased C3, elevated BUN and creatinine.
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Describe the basic manifestation of Rapidly Progressive (Crescentic) Glomerulonephritis.
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Severe glomerular injury. Rapid and progressive loss of renal function with severe oliguria and death in weeks to months if untreated.
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What are the three types of Rapidly Progressive (Crescentic)Glomerulonephritis and list examples.
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Type 1- 20%- Anti-GBM antibody EX: Goodpasture
Type 2- 25% Immune complex EX: idiopathic, Henoch- Schonlein purpura Type 3- 50% Pauci immune- ANCA associated, idiopathic, Wegners, Microscopic polyarteritis nodosa/ microscopic polyangittis |
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Describe type 1 Rapidly Progressive (Crescentic) Glomerulonephritis.
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Antibody against glomerular BM. Some patients have cross reaction w/pulmonary alveolar basement membranes. Can treat with plasmaphersis
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What is Goodpasture syndrome ?
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It is a type 1 Rapidly Progressive (Crescentic) Glomerulonephritis with pulmonary hemorrhage associated with its renal failure.
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What is the antigen in Goodpasture syndrome?
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The antigen is a peptide within the noncollagenous portion of th alpha3 chain of collagen type IV. What triggers the antobody formation is unknown
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Describe Rapidly Progressive (Crescentic) Glomerulonephritis type 2.
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It is immune complexes that are often a complication of immune comples nephritis realted to several various etiologies ( postinfectios, SLE, IgA nephropathy ect)
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Describe Rapidly Progressive (Crescentic) Glomerulonephritis type 3.
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There are no anti-GBM or immune complexes. ANCAs are found in the serum ( p-ANCA and c-ANCA). It can be idiopathic or related to systemic vasculistis.
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What is the gross appearence of the kidneys in Rapidly Progressive (Crescentic) Glomerulonephritis.
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The kidneys are enlarges,pale,often with petechial hemorrhages on cortical surface,
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What is the classic finding in Rapidly Progressive (Crescentic) Glomerulonephritis?
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Crescent formation- formed by proliferation of parietal cells and influx of macrophages/monocytes into urinary space leading to the eventual obliteration of Bowman's space.
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What are the IF results for all three types of Rapidly Progressive (Crescentic) Glomerulonephritis.
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Type 1- linear IgG and C3 in BM
Type 2- Granular deposition- lumpy bumpy Type 3- negative |
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What are the EM findings in Rapidly Progressive (Crescentic) Glomerulonephritis.
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Rupture in the GBM secondary to severe injury
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What are the clinical manifestations of Rapidly Progressive (Crescentic) Glomerulonephritis.
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rapid declin in renal function, severe oliguria or anuria, hematuria, red cell casts, modereate proteinuria, HTN, edema.
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What is the most common type of glomerulonephritis in the world?
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IgA Nephropathy aka Berger's disease
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Is IgA Nephropathy primary, seocndary or both?
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Both. Primary as component of Henoch-Schonlein purpura. Secondary to liver disease, IBD, celiacs and HIV
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What is the etiology of IgA Nephropathy?
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It is immune mediated- thought to be caused by the generation of nephrogenic IgA Ab derived from mucosal antigen exposure that form immune complexes in the circulation and deposit in the mesangium complexed with C3.
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What are the clinical manifestations of IgA Nephropathy?
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Usually an older child or young adult. Presents with gross or microscopic hematuria during or shortly after URI. Hematuria lasts for several days then subsides and returns every few months.
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What is the LM of IgA Nephropathy?
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Varies. Normal to mesangial widening and proliferation.
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What are the IF results of IgA Nephropathy?
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Mesangial IgA usually codeposits with C3, can extend to loops
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What are the EM results for IgA Nephropathy?
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Mesangial or paramesangial electron deposits
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What age group is affected by Henoch-Schonlein Purpura?
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Children 3-8 yo
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What is the etiology of Henoch-Schonlein Purpura?
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systemic IgA- mediated vasculitis. IgA is deposited in glomerular mesangium
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What are the clinical manifestation of Henoch- Schonlein Purpura?
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Syndrome consists of purpuric skin lesions over extensor surface of arms, legs, buttock. Abdominal manifestations include pain, vomiting and intestinal bleeding: nonmigratory arthralgia. Renal manifestations in 1/3 which includes gorss or microscopic hematuria, proteinuria, nephrotic sydrome. Usually has good prognosis.
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What are the LM results of Henoch-Schonlein purpura?
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Mild focal to diffuse mesangial proliferation
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What are the IF results of Henoch-Schonlein purpura?
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Depostion of IgA in mesangial region
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What is the cause of Benign Familial Hematuria?
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Benign Familial Hematuria or Thin Basement Membrane Disease is caused by defects in the genes for alpha 3 and 4 chains of type 4 collagen causing there to be a thinned glomerular BM of 150-200 nm
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What is the clinical presentation of Benign familial hematuria?
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Asymptomatic hematuria, occasional mild proteinuria. There is normal renal function and microscopic hematuria is found on routine urinalysis.
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What is the cause of Alport Syndrome?
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Usually X-linked dominant that causes defective GBM synthesis from a mutation in the alpha5 chain of type 4 collagen
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What are the clinical manifestations of Alport Syndrome?
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Recurrent micro or macrohematuria , varying proteinuria, sensorineurak deafness, cataracts, lens dislocation, slow progression to renal failure. Males are more seriously effected.
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What are the LM results in Alport Syndrome?
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Mesangial hypercellularity and/or scarring, usually mild, segmental. Tubular atrophy and interstial fibrosis. Interstial foam cells are common
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What are the EM findings of Alport syndrome?
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BM thinning alternating with thickening, splitting of the BM, lamination of the lamina densa with basket weave appearance.
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What are the IF results in Alport Syndrome?
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Negative
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Describe SLE affects on the kidneys.
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50% of pts with SLE have glomerulonephritis. IF shoes measngial and peripheral granular IgG,IgA,IgM and complement. The EM all show mesangial deposits. renal failure is one of the most common cause of death.
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Describe diabetes effect on the kidneys.
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DM causes hyalinizing arteriolar sclerosis, capillary BM thickening and mesangial sclerosis and nodular glomerulosclerosis (Kimmerlsteil-Wilson disease).
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Describe amyloidosis on the kidney
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Usually light chain amyloid AL and AA
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What is chronic glomerulonephritis?
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It is the end-stage of various disease with the same microscopic appearence
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What are the microscopic findings of chronic glomerulonephritis?
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Glomeruli are completely effaced by hyalinized connective tissue. Vascular sclerosis may be prominents
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What is the most common cause of acute renal failure?
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Acute Tubular Necrosis
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What are the 2 major etiologies of acute tubular necrosis?
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Toxins and posions in the tubules and ischemia often from hypotension
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What are the 3 critical event in acute tubular necrosis?
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1. Tubular injury wuth leakgae if tubular fluis into the interstitium and tubular obstruction with cast like material
2. Persistent and severe disturbances in blood flow 3.Abn glomerular permeability |
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What do the kidneys look like grossly in acute tubular necrosis?
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Increase in size and weight
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What area of the kidney is involved in ischemic ATN?
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Straight portion of the PT and thick ascending LH
There are patchy focal tubular necrosis with skip areas. Cast occulde lumen. Edema and leukocytes. Area of epithelial regeneration |
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What area of the kidney is involved in Toxic ATN?
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Proximal convulted tubule. It is more diffuse then ischemic
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What is the LM of ATN?
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There is epithelial death and tubular cast. Epithelial cell slough. Regenerative changes with mitotic figures
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What is the clinical course of ATN?
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1. intiation- 36hrs decreas in urine
2.maintence- sustained decreases in urine output with worsening renal function, uremia and metabolic disturbances 3.recovery- steady increase in urine volume |
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Who has a better outcome toxic ATN or ischemic ATN?
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Toxic
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