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316 Cards in this Set
- Front
- Back
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list the congenital abnormalities of the urinary tract |
1. Kidney: |
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complete or bilateral renal agenesis
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- not compatible with life |
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what is the oligohyramnios or Potter sequence?
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- conditions caused by oligohydramios
- hypoplastic lung - defects in extremities |
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what congenital defects result from hyperhydramnios?
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- duodenal atresia
- tracheoesophageal fistula (upper esophagus ends in a blind pouch; lower esophagus communicates with the trachea) |
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what is unilateral renal agenesis? how common is it?
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- one missing kidney
- more common than bilateral renal agenesis |
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what is renal ectopia
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- abnormal kidney location
- frequently in the pelvis (pelvic kidney) |
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what is horseshoe kidney
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- two kidneys joined at lower poles
- may cause urinary tract obstruction from impingement on the ureters |
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what do double ureters indicate?
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- may only affect the ureters, or may be part of a duplication of the entirely urinary collecting system on one side
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define nephrotic syndrome
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- group of conditiosn characterized by increased BM permeability -> urinary loss of proteins (esp. low weight proteins like albumin)
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what are the clinical manifestations of nephrotic syndrome?
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1. massive proteinuria
2. hypoalbuminemia 3. generalized edema 4. hyperlipidemia and hypercholesterolemia |
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list the disorders of the nephrotic syndrome
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1. minimal change disease
2. focal segmental glomerulosclerosis 3. membranous glomerulonephritis 4. Diabetic nephropathy 5. renal amyloidosis 6. lupus nephropathy |
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what defines massive proteinuria?
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- excretion of more than 4 grams of protein per day
- in the nephrotic syndrome, is not accompanied by RBCs and white cell urine secretion |
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what defines hypoalbuminemia?
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- results from proteinuria
- makred by serum concentration of less than 3g/100ml |
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why do you get generalized edema in nephrotic syndrome?
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- decreased plasma colloid oncotic pressure
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why do you get hyperlipidemia and hypercholesterolemia in neprhotic syndrome?
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- increased hepatic lipoprotein synthesis
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who gets minimal change disease?
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- aka lipoid neprhosis
- seem in young children. sometimes seen in older children and adults - PROTOTYPE of nephrotic syndrome |
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what characterizes minimal change disease?
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- lipid laden renal corticies
- normal appearing glomeruli under light microscopy - fusing of epithelial foot processes under electron microscopy |
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how do you treat minimal change disease?
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- adrenal steroid therapy
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describe the lipid laden renal corticies seen in minimal change disease
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- lipids are intracytoplasmic in tubular cells, particularly in cells of the proximal convoluted tubules
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what is the clinical presentation of focal segmental glomerulosclerosis?
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- clinically similar to minimal change disease, but occurs in OLDER patients
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what characterizes focal segmental glomerulosclerosis?
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- sclerosis within capillary tufts of deep juxtamedullary glomeruli with focal or segmental distribution
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what does the 'focal' and 'segmental' parts mean in focal segmental glomerulosclerosis?
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1. focal distribution: involves some, but not all, glomeruli
2. segmental distribution: involves only part of the glomerulus |
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what causes membranous glomerulonephritis?
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- immune complex disease of unknown etiology
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what disease is a major PRIMARY cause of nephrotic sydrome?
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- membranous glomerulonephritis
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what is the incidence of membranous glomerulonephritis?
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- incidence is highest in teenagers and young adults
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what should you suspect when you have nephrotic syndrome accompanied by azotemia?
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- membranous glomerulonephritis
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what is azotemia?
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- increased serum concentrations of urea, nitrogen, and creatitinine
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what are morphological changes you see in membranous glomerulonephritis?
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- thickened capillary walls (seen in light microscopy)
- in electron microscophy, seen as a 5-10 fold thickening of the BM |
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what are ultrastructural findings of membranous glomerulonephritis?
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- immune complexes in the intramembranous and epimembranous (subepithelial) locations within and on the BM
- can see a 'spike a dome' appearance with special stains (spikes: BM material; domes: immune complex deposits) |
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what is the 'spike and dome' appearance?
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- seen in membranous glomerulonephritis with the use of special stains
- results from the extension of BM between and around the immune deposits |
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what is granular immunofluorescence characteristic of?
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- immune complex disease
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- what do you see in membranous glomerulonephritis using immunofluorescence?
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- granular deposits of IgG or C3
- granular immunofluorescence is generally characteristic of immune complex disease |
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what is the clincial progression of membranous glomerulonephritis?
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- slowly progressing disorder
- no response to steroid therapy |
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what is membranous glomerulonephritis associated with?
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- seen in 10% of patients with SLE
- other associations: - hep B - syphilis - malarial infection - drugs (gold salts or penicillamine) - malignancy |
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what can membranous glomerulonephritis sometimes cause in the kidney?
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- renal vein thrombosis
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what do you see with diabetic nephropathy on electron microscopy?
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- increase in thickness of the glomerular basement membrane
- thickening of vascular basement membranes observable by EM is one of the earliest changes seen in DM |
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what 2 characteristic morphologic patterns do you see with an increase in mesangial matrix in diabetic nephropathy?
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1. diffuse glomerulosclerosis: marked by diffusely distributed increase in mesangial matrix
2. Nodular glomerulosclerosis: marked by nodular accumulations of mesangial matrix material |
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what are Kimmelsteil-Wilson nodules?
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- nodular accumulations of mesangial matrix materials
- seen in diabetic nephropathy |
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what do you see in renal amyloidosis?
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- subendothelial and mesangial amyloid deposits
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how can you identify renal amyloidosis with lab tests?
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- look at reactivity of amyloid with special stains (Congo red, crystal violet, thiofavin T) and by birefringence under polarized light
- alos demonstrated by criss-cross fibrillary pattern of amyloid by EM |
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what is renal amyloidosis associated with?
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- chornic inflammatory diseases like Rheumatoid arthritis, or
- plasma cell disorders (e.g. multiple myeloma) |
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what is lupus nephropathy?
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- the renal component of SLE
- while it often presents as the nephrotic syndrome, it can also present with nephritic features |
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what are the five renal patterns seen in lupus nephropathy?
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- Types I - V
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what is Type I lupus nephropathy?
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- no observable renal involvement
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wha is Type II lupus nephropathy?
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- mesangial form
- focal and segemnetal glomerular invovlemtn with an increase in the number of sesangila cells and quantitative increase in mesangial matrix - often will have slight proteinuria and minimal hematuria - little clincial consequence |
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what is Type III lupus nephropathy?
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-focal proliferative form
- usually involves >50% of glomeruli, but can cause extensive damage to individual glomeruli |
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what is Type IV lupus nephropathy?
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- diffuse proliferative form
- prototype of lupus nephropathy and most severe form of the disease - often, a combo of nephrotic and nephritic syndromes - almost all glomeruli are involved - glomerular changes - 'wire-loop' abnormality - endothelial cell proliferations - subendothelial immune complex deposition |
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what are the glomerular changes seen in lupus nephropathy?
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- marked inflammation with focal thromboses and mesangial proliferation -> extensive scaring
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what is the 'wire-loop' abnormality seen in lupus nephropathy?
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- light microscopic finding resulting from immune complex deposition and gross thickening of the glomerular BM
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how do you observe endothelial cell proliferation, as seen in lupus nephropathy?
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- EM
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what is a major diagnostic feature of Type IV lupus nephropathy?
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- subendothelial immune complex deposition
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what is Type IV lupus nephropathy?
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- indistinguishable from primary membranous glomerulonephritis.
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what is the nephritic syndrome?
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- inflammatory rupture of the glomerular capillaries -> bleeding into the urinary space
- proteinuria and edema may be present, but are usually mild |
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what are the clinical findings of nephritic syndrome?
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- oliguria
- azotemia - hypertension - hematuria |
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why do you get hematuria with nephritic syndrome?
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- leakage of RBCs directly from glomerular capillaries into the Bowman space
- RBCs aggregate in the tubules, and form red cell casts (often seen in urine) - patient can report 'smoky brown urine' |
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what can RBC casts degenerate into?
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- pigmented granular casts
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what disesases may present with nephritic syndrome?
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- poststreptococcal glomeruloneprhitis
- rapidly progressive (crescentic) glomerulonephritis - goodpasture syndrome - Alport syndrome |
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list the other glomerular disorders that don't display either nephrotic or nephritic symptoms
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- IgA nephropathy (Berger disease)
- Membranoproliferative glomerulonephritis |
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which disease is the prototype of nephritic syndrome?
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poststreptococcal glomerulonephritis
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what causes poststreptococcal glomerulonephritis?
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- aka acute proliferative glomerulonephritis
- immune complex disease with antigen of streptococcal origin |
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when do you get poststreptococcal glomerulonephritis?
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- follows or accompanies infection with nephritogenic strains of group A b-hemolytic streptococci
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which types of infections are caused by group A b-hemolytic streptococci?
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- tonsillitis
- streptococcal impetigo - infected insect bites |
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what is the clinical course of poststreptococcal glomerulonephritis?
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- complete recovery in almost all children and adults
- small fraction develop rapidly progressive glomerulonephritis |
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what are the lab abnormalities seen in poststreptococcal glomerulonephritis?
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- urinary RBCs and casts
- azotemia - decreased serum C3 - increased titers of antistreptococcal antibodies |
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name the atistreptococcal antibodies seen in poststreptococcal glomerulonephritis?
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- antistreptolysin O (ASO)
- anti-DNAase B - anticationic proteinase |
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describe the kidney reaction to poststreptococcal glomerulonephritis?
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- intesne inflammatory reaction involving almost all glomeruli in both kidnies
1. innumerable punctate hermorrhages on the kidney surface 2. enlarged, hypercellular, swollen, bloodless glomeruli 3. electron-dense humps 4. lumpy-bumpy immmunoflurescence |
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tell me more about the enlarged, hypercellular, swollen, bloodless glomeruli seen in poststreptococcal glomerulonephritis
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enlarged, hypercellular, swollen, bloodless glomeruli with proliferation of mesangial and endothelial cells and sometimes neutrophils
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how does the glomerular BM appear in poststreptococcal glomerulonephritis?
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- normal thickness and uniformity despite extensive inflammatory changes
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describe the electron-dense 'humps' seen in poststreptococcal glomerulonephritis
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- found on the epithelial side of the BM (subepithelial localization)
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describe the lumpy-bumpy immunofluorescence seen in poststreptococcal glomerulonephritis
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- extremely coarse granular immunofluorescence for IgG or C3
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Rapidly progressive (crescentic) glomerulonephritis (RPGN), by definition
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- the nephritic syndrome that progresses rapidly to renal failure within weeks or months
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what is the histology of Rapidly progressive (crescentic) glomerulonephritis (RPGN)?
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- formation of crescents betweenthe bowman capsule and the glomerular tuft. caused by:
1. the deposition of fibrin in the Bowman space 2. proliferation of parietal epithelial cells of the bowman capsule - cells of monocytic origin are often involved |
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what is the etiology of Rapidly progressive (crescentic) glomerulonephritis (RPGN)?
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- poststreptococal
- 50% of cases have immune complex deposition |
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what are other immune complex forms of Rapidly progressive (crescentic) glomerulonephritis (RPGN)?
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- lupus nephropathy
- IgA nephropathy |
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what do you see in ~10% of the cases of Rapidly progressive (crescentic) glomerulonephritis (RPGN)?
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- antiglomerular BM antibodies (nonstreptococcal)
- often present clinically as Goodpasture syndrome |
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what is the pauci-immune type of Rapidly progressive (crescentic) glomerulonephritis (RPGN)?
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- no immune complex deposition or antiglomerular basement membrane antibodies
- associated with ANCAs |
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what is type I Rapidly progressive (crescentic) glomerulonephritis (RPGN)?
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ANCA-negative form of RPGN when RPGN is of the antiglomerular BM membrane antibody
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what is type II Rapidly progressive (crescentic) glomerulonephritis (RPGN)?
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ANCA-negative form of RPGN when RPGN is of the immune complex type
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what is type III Rapidly progressive (crescentic) glomerulonephritis (RPGN)?
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ANCA positive pauci-immune form of RPGN
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what causes Goodpasture syndrome?
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- aka antiglomerular basement membrane disease
- caused by antibodies directed against antigens in glomerular and pulmonary alveolar basement membranes |
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what type of fluorescence is demonstrated by antibody studies for IgG in Goodpasture syndrome?
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- linear immunofluorescence
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what are the clinical manifestations of Goodpasture syndrome?
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- Nephritic syndrome
- pneumonitis with hemoptysis - RPGN crescentic morphology with linear immunofluorescence |
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what is the peak incidence of Goodpasture syndrome?
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- men in mid-20s
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how does focal glomerulonephritis differ from focal segmental glomerulosclerosis?
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- focal and segmental, but is different from focal esgmetnal glomerulosclerosis in that changes are inflammatory and proliferative rather than sclerotic
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what causes focal glomerulonephritis?
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- immune complex disease
- occurs as a manifestation of many disorders: - SLE - subacute bacterial endocarditis - polyarteritis nodosa - Goodpasture syndrome - Wegener granulomatosis - IgA nephropathy - can also be idiopathic |
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what is Alport syndrome?
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- hereditary nephritis associated with nerve deafness and ocular disorders (e.g. lens dislocation and cataracts)
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describe the clinical course of Alport syndrome
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- clinical characteristics include the nephritic syndrome, often progressing to end-stage renal disease by 30 years of age
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what causes Alport syndrome?
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- mutation in the gene for the a5 chain of type IV collagen
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what do you see with microscopy in Alport syndrome?
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- irregular glomerular basement membrane thickening with foci of splitting of the lamina densa
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what is IgA nephropathy?
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- aka Berger disease
- very common - deposition of IgA in the mesangium |
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hos is IgA nephropathy most frequently characterized?
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- benign recurrent hematuria in children, folling an infection
- lasts 1-2 days (minimal clinical significance) - focal glomerulonephritis |
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in which disease can IgA nephropathy be a component of?
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Henoch-Schonlein disease
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what is membranoproliferative glomerulonephritis?
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- glomerular basement reduplication into two laters from the expansion of mesangial matrix into the capillary loops -> 'tram-track' appearance seen with silver stains
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what does membranoproliferative glomerulonephritis progress to?
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- chronic renal disease
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what are the histologic characteristics of membranoproliferative glomerulonephritis?
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- basement membrane thickening
- cellular proliferation |
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what disease features a 'tram-track' appearance?
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membranoproliferative glomerulonephritis
- seen with silver staining |
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what are the two forms of membranoproliferative glomerulonephritis?
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1. Type I: immune complex nephritis associated with unknown antigen (tram-track)
2. Type II (dense-deposit disease). |
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describe type II membranoproliferative glomerulonephritis
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- tram-track appearance that's not as appearant as that of type I
- electron-desne material deposited within the glomerular BM - C3 is demonstrable adjacent to the dense deposits - C3 in serum is reduced |
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what is a possible cause of type II membranoproliferative glomerulonephritis?
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- IgG autoantibodie (C3 nephritic factor) with specificity for the C3 convertase of the alternate complement pathway
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what is the most often cause of urinary path obstruction in children?
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- congenital
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what is the most often cause of urinary path obstruction in adults?
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- usually acquired
- consequence of renal stones or benign prostatic hyperplasia |
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what are the clinical manifestations of urinary path obstruction?
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- renal colic
- hydronephrosis - infection |
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what is renal colic?
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- pain cuased by acute distention of the ureter, usually by the transit of a small stone
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what is hydronephrosis?
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- progressive dilation of the renal pelvis and calyces
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describe infection in the setting of urinary tract obstruction
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- localized proximal to the site of obstruction
- may lead to infection of the renal parenchyma |
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what is the incidence of UTI and kidney infection?
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- higher in women b/c of shortened ureter
- increased incidence during pregnancy |
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what bacteria most frequently causes UTIs?
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- E. coli from the colon
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how does the UTI spread from the bladder into the ureters?
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- vesicoureteral reflux
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what are predisposing factors to UTIs?
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- obstruction of urinary flow (BPH)
- surgery on kidney or urinary tract - catheters in urethra into bladder - gynecologic abnormalities |
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what are the clinical manifestations of UTIs?
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- urinary frequency
- dysuria - pyuria - hematuria - bacteriuria |
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define: dysuria
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- painful, burning sensation during urination
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define: pyuria
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- large numbers of neutrophils in the urine
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define: hematuria
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- blood in urine
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define: bacteriuria
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- more than 10^5 organisms per milliliter of urine
- make sure it's not from external contamination |
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what is acute pyelonephritis?
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- acute infection of the renal parenchyma
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what are diagnostically significant findings in acute pyelonephritis?
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- fever
- leukocytosis - flank tenderness - urinary white cells - white cell casts in the urine |
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what are white cell casts in the urine pathognomonic for?
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- acute pyelonephritis
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what's cystitis?
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- infection of the bladder
- pyuria, and often hematuria - urinary white cell casts are not found |
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what causes acute drug-induced interstitial nephritis?
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- penicillin derivatives (e.g. methicillin)and other drugs (NSAIDs and diuretics)
- likely of immune etiology |
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what is characteristic of acute drug-indiced interstitial nephritis?
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- acute interstitial renal inflammtion
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how do you treat acute drug-indiced interstitial nephritis?
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- stop giving the inciting drug
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what is renal papillary necrosis?
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- aka necrotizing papillitis
- ischemic necrosis of the tips of renal papillae |
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what is renal papillary necrosis most often associated with?
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- DM (renal infection and coexisting vascular disease)
- occasionally a catastrophic consequence of acute pyelonephritis |
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what is renal papillary necrosis associated with (other than DM)?
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- long term abuse of phenacetin -> leads to chronic analgesic nephritis
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what is chronic analgesic nephritis?
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- chronic inflammatory change characterized by loss and atrophy of tubules and intersitial fibrosis and inflammation
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phenacetin
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introduced in 1887, was used principally as an analgesic. It was the very first NSAID and fever reducer to go on the market.
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what is acute tubular necrosis the most common cause of?
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- most common cause of acute renal failure
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is acute tubular necrosis reversible?
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- yes. necrotic renal tubular cells are replaced by new cells in 2 wks
- complete renal function returns if patient is maintained on dialysis |
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what are the cardiac effects of acute tubular necrosis?
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- cardiac standstill from hyperkalemia, during the initial oliguric phase
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define: oliguria
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Oliguria and anuria are the decreased or absent production of urine, respectively.
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what is the acute condition of acute tubular necrosis most frequently precipitated by?
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- renal ischemia caused by hypotension or shock induced by gram neg sepsis, trauma, or hemorrhage
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what is another condition associated with acute tubular necrosis?
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- crush injury with myoglobinuria
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when can you observe myoglobinuria?
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- during exercise
- with acute tubular necrosis |
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what are some other causes of acute tubular necrosis (toxic)?
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- direct injury to the proximal renal tubules from mercuric chloride and gentamicin
- ethylene glycol |
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what can ethylene glycol cause?
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- acute tubular necrosis
- renal oxalosis with massive intratubular oxalate crystal deposition which can be seen in polarized light |
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describe Fanconi syndrome
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- generalized dysfunction of the proximal renal tubules
- hereditary or acquired - impaired absorption of glucose, amino acides, phosphate and bicarb |
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what impairments in absorption do you get with Fanconi syndrome?
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- impaired absorption of glucose, amino acides, phosphate and bicarb
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what are the clinical manifestations of Fanconi syndrome?
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- glycosuria
- hyperphosphaturia - hypophosphatemia - aminoaciduria - systemic acidosis |
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what is cystinuria?
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- genetically determined
- impaired tubular reabsorption of cystine |
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what is the clinical manifestion of cystinuria?
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- cystine stones
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what is hartnup disease?
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- impiared tubular reabsorption of tryptophan
- genetically determined - leads to pellagra-like manifestations |
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what is pellagra?
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Pellagra is a vitamin deficiency disease caused by dietary lack of niacin (vitamin B3) and protein, especially proteins containing the essential amino acid tryptophan.[1] Because tryptophan can be converted into niacin, foods with tryptophan but without niacin, such as milk, prevent pellagra.
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what are the clinical symptoms of pellagra?
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The main results of pellagra can easily be remembered as "the four D's": diarrhea, dermatitis, dementia, and death
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describe chronic pyelonephritis?
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- coarse, asymmetryc corticomedullary scarring adn deformity of the renal pelvis
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what characterizes chronic pyelonephritis in the early and late stages?
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- interstitial inflammatory infiltrate in the early stages
- late stages: interstitial fibrosis and tubular atrophy |
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what do you see in the interstitial fibrosis and tubular atrophy that mark the later stages of chronic phelonephritis?
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- eosinophilic proteinaceous casts
- look like thyroid follicles (thyroidization of the kidney) |
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what disease causes thyroidization of the kidney?
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- chronic pyelonephritis
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what causes chronic pyelonephritis?
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- chronic urinary tract obstruction and repeated bouts of inflammation
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what are the long term consequences of chronic pyelonephritis?
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- renal hypertension
- end stage renal disease |
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what characterizes diffuse cortical necrosis?
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- generalized ischemic infarction of the cortices of both kidneys
- spares the medulla - infarction is patchy, and sometimes compatible with survival |
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what is diffuse cortical necrosis most often associted with?
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- obstetric catastrophes (e.g. abruptio placentae, or eclampsia)
- also associated with septic shock and other causes of vascular collapse |
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what causes diffuse cortical necrosis?
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- combination of end-organ vasospasm and DIC
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what is nephrocalcinosis?
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- diffuse Ca deposition in the kidneys that can lead to renal failure
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what is nephrocalcinosis caused by?
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- hypercalcemia, as seen in hyperparathyrodism, or in the milk-alkali syndrome
- hyperphosphatemia |
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what is the milk-alkali sydrome?
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- nephrocalcinosis and reanl stomes resulting from self-medication for peptic ulcer with milk and absorbable antacids
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what is interesting about nephrocalcinosis and renal failure?
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- can be both the effect and cause of renal failure
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what is urolithiasis?
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- calculi (stones) in the urinary tract
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what is the incidence of urolithiasis?
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- increased incidence in men
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describe calcium stones
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- made of calcium oxalate or calcium phosphate, or both
- radiopaque |
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what are most urinary stones made of?
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- Calcium stones make up 80-85% of urinary stones
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what are calcium stones associated with?
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- hypercalciuria, caused by
1. increased absorption of Ca 2. increased renal excretion of Ca 3. hypercalcemia |
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what causes hypercalcemia?
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- hyperparathyroidism
- malignancy - sarcoidosis, vit D intoxication, and the milk-alkali syndrome |
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how does hyperparathyroidism cause hypercalcemia?
|
- leads to nephrocalcinois (calcification of the kidney and urolithiasis)
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how does malignancy cause hypercalcemia?
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- osteolytic metasteses or ectopic production of parathyroid hormone (via squamous cell carcinoma of the lung) cause hypercalcemia
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what are the second most common form of urinary stones?
|
- ammonium magnesium phosphate stones
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describe ammonium magnesium phosphate stones
|
- formed in alkaline urine
- radiolucent - can form large staghorn (struvite) calculi- casts of renal pelvis and calyces |
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how do you get alkaline urine?
|
- caused by ammonia producing (urease-positive) organisms (proteus vulgaris, and staphylococcus)
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what are uric acid stones associated with?
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- hyperuricemia in 50% of patients
- hyperuricemia can be secondary to gout, or increased cellular turnover (seen in leukemias and myeloproliferative syndromes) |
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what are cysteine stones assocaiated with?
|
- cystinuria or genetically determined aminoaciduria
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when does adult polycystic kidney disease present?
|
- between 15-30
- defect is present at birth however |
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what is the inheritance pattern of polycystic kidney disease?
|
- autosomal dominant
- most common inherited disorder of the kidney |
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what do you see in polycystic kidney disease?
|
- partial replacement of renal parenchyma by cysts
- occurs bilaterally - kidneys are enlarged |
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what is polycystic kidney disease associated with?
|
- berry aneurysms of the circle of Willis
- cystic disease of the liver and other organs |
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what can you secondarily to polycystic kidney disease?
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- secondary polycythemia
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define: polycythemia
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abnormally high level of red blood cells in the circulating blood.
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what are the clinical manifestations of polycystic kidney disease?
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- hypertension
- hematuria - palpable renal masses - progression to renal failure |
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what is infantile polycystic kidney disease?
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- multiple cysts evident at birth
- closed cysts not in continuity with the collecting system - autosomal recessive - death shortly after birth |
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what is a simple (solitary) renal cyst?
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- common lesion in adults
- often asymptomatic |
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what is uremic medullary cystic disease?
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- aka nephronophthisis
- very serious (but rare) form of cystic disease that affects older children - characterized by cysts in the medulla -> renal failure |
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what characterizes medullary sponge kidney?
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- multiple small medullary cysts and impaired tubular function
- no renal failure - renal stones can form in dilated ducts - can be complicated by infection |
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what is acquired cystic disease?
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- associated with long-term dialysis therapy
- myltiple cysts, glomerular and tubular atrophy - scarring |
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what type of cancer are you more at risk for with aquired cystic disease?
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- renal cell carcinoma
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what is always associated with renal failure?
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- azotemia of renal origin
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define: azotemia
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Abnormally high concentrations of urea and other nitrogenous substances in the blood.
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what happens in advanced stages of renal failure?
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- uremia
- uremia denotes the biochem and clinical syndrome characteristic of symptomatic renal disease |
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what are the major clinical characteristics of uremia?
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- azotemia
- acidosis - hyperkalemia - abnomrla control of fluid volume - hypocalcemia - anemia - hypertension |
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why do you get acidosis with renal failure?
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- accumulation of sulfates, phosphates, and organic acids
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describe the abnormal control of fluid volume seen with renal failure
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- early characteristic: inability to concentrate urine
- late: inability to dilute urine - Na and water retention -> heart failure |
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why do you get hypocalcemia in renal failure?
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- unable to synthesize active form of vitD
- hypocalcemia can lead to renal osteodystrophy |
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what is renal osteodystrophy?
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The mineral content of bone is Ca hydroxyapatite. When Ca is being actively resorbed from bone, the PO4 also enters the blood stream. The kidney is the primary means of excreting excess phosphate
- Renal osteodystrophy results from hyperphosphatemi and hypocalcemia, both of which are due to decreased excretion of phosphate by the damaged kidney, low vitD levels or tertiary hyperparathyroidism |
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why do you get anemia with renal failure?
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- decreased secretion of erythropoietin
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why do you get hypertension with renal failure?
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- hyperproduction of renin
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what are other clinical characteristics of uremia?
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- anorexia
- neurologic disorders (diminished mental function, and convulsions, coma) - bleeding from decreased platelet function - accumulation in the skin of urochrome - fibrinous pericarditis |
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what causes prerenal azotemia?
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- decreased renal blood flow caused by:
- blood loss - decreased CO - systemic hypovolemia, or - peripheral pooling of blood due to marked vasodilation (gram - sepsis) |
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what are the non-renal causes of azotemia?
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1. prerenal azotemia
2. postrenal azotemia |
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what characterizes prerenal azotemia?
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- increasd tubular reabsorption of sodium and water -> oliguria, concentrated urin, and decreased urinary sodium excretion
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what causes postrenal azotemia?
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- blockage or urinary flow
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how do you characterize oliguria of shock as seen in prerenal azotemia?
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- can be caused by decreased renal blood flow -> decreased GFR -> tubular reabsorption of sodium is maximally increased and urinary sodium is low
- can also be caused by a manifestation of acute tubular necrosis: tubular reabsorption is impaired and urinary sodium is not decreased |
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what is the BUN:creatinine level in prerenal azotemia?
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- greater than 15 do to both:
1. decreased GFR 2. increased tubular reabsorption of urea |
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what are the benign tumors of the kidney?
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1. adenoma
2. angiomyolipoma |
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what is adenoma of the kidney?
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- small and asymptomatic
- derived from renal tubules - may be a precursor lesion to renal carcinoma |
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what is renal angiomyolipoma?
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- hamartoma consisting of fat, smooth muslce, and blood vessels
- often associated with tuberous sclerosis sydrome |
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what is tuberous sclerosis syndrome associated with?
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1. rhabdomyoma
2. angiomyolipoma of the kidney |
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list the malignant tumors of the kidney
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1. renal cell carcinoma
2. wilms tumor 3. transitional cell carcinoma 4. squamous cell carcinoma |
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what is the most common renal malignancy?
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- renal cell carcinoma
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what is the incidence of renal cell carcinoma?
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- more common in men
- 50-70 years of age - higher incidence in smokers |
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what genetic defects are associated with renal cell carcinoma?
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- sometimes, associated with gene deletions on chr3.
- can also be associated with von Hippel-Lindau disease (caused by alterations in gene on chr3) |
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what is von Hippel-Lindau disease?
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Von Hippel-Lindau disease (VHL) is a rare inherited genetic condition involving the abnormal growth of tumors in parts of the body which are particularly rich in blood supply.
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where do renal cell carcinomas originate?
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- renal tubules
- most often, it arises in one of the renal poles (usually the upper pole) |
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where do renal cell carcinomas invade?
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- into renal veins, or vena cava and can extend up the vena cava
- early hematogenous dissemination can occur |
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what are histologic characteristics of renal cell carcinomas?
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- polygonal clear cells, sometimes with vestigial tubule formation
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what are the clinical symptoms of renal cell carcinoma?
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- triad of flank pain, palpable mass, and hematuria (hematuria is the most common presenting abnormality)
- fever - secondary polycythemia (from EPO production) - ectopic production of various hormones |
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what types of ectopic hormone production can you see with renal cell carcinoma?
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- ACTH
- prolactin - gonadotropins - renin - paraneoplastic parathyroid-like hormone can also cause hypercalcemia |
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what is the incidence of Wilms tumor?
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- aka nephroblastoma
- most common renal malignancy of early childhood - incidence peaks at 2-4 years of age |
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where does Wilms tumor originate from?
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- primitive metanephric tissue
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what are the histologic characteristics of Wilms tumor?
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- immature stroma, primitive tubules and glomeruli
- mesenchymal elements like fibrous connective tissue, cartilage, bone, and rarely, striated muscle |
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what is the presenting feature of a wilms tumor?
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- palpable flank mass (often huge!)
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what are the genetics behind wilms tumor?
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- associated with the short arm of chr 11
- the WT-1 and WT-2 genes localized to this chr are cancer suppressor genes |
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what is the AGR (or WAGR) complex?
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- Wilms tumor
- Aniridia - genitourinary malformations - mental motor Retardation |
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define: aniridia
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Absent or partially absent iris, typically congenital. Additional symptoms include poor vision and photophobia.
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what is the ARG complex associated with?
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- deletion of the WT-1 tumor suppressor gene, adn other nearby genes
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what is the Denys-Drash syndrome?
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- abnormalities of the WT-1 gene
- intersexual disorders - nephropathy - Wilms tumor |
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what else is Wilms tumor associated with?
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- hemihypertrophy
- macroglossia - organomegaly - neonatal hypoglycemia - various embryonal tumors - this set of anomalies (with Wilms tumor): Beckwith-Wiedemann sydrome |
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what is the Beckwith-Wiedemann syndrome?
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- hemihypertrophy
- macroglossia - organomegaly - neonatal hypoglycemia - various embryonal tumors - Wilms tumor - associated with deletion of the WT-2 gene |
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give an example of maternal imprinting
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- beckwith-wiedemann syndrome
- abnormal alleles are always of maternal origin |
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where does transitional cell carcinoma most frequently occur?
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- most common tumor of the urinary collecting system
- can occur in renal calyces, pelvis, ureter, or bladder - often multifocal in origin |
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wha is transitional cell carcinoma in the renal pelvis associated with?
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- phenacetin abuse
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what is the recurrence rate of transitional cell carcinoma after removal?
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- high
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what is the presenting feature of transitional cell carcinoma?
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- hematuria
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what is the progression of transitional cell carcinoma?
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- tendency to spread by local extension to surrounding tissues
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what associated toxic exposures are seen with transitional cell carcinoma?
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- industrial exposure to benzidine or b-naphthylamine (an aniline dye)
- smoking - long term treatment with cyclophosphamide |
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what is squamous cell carcinoma?
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- constitutes a minority of Urinary tract maligancies
- results from chronic inflammatory processes (e.g. chronic bacterial infection, or Schistosoma haematobium infection) - can also be associated with renal calculi |
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what is a calculi?
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- stone
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name three hormones produced by the kidney
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- renin
- calcitriol - EPO |
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what is calcitriol?
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- metabolite of vit D
- needed for normla reabsorption of Ca in the GI tract, and for its deposition in bone |
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what is one of the causes of anemia in chronic renal failure?
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- lack of EPO production
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what do minor calyces do?
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- collect urine from each papilla
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where is the brush border of the kidney located?
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- PT
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describe the anatomy of the proximal tubule
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- brush border on the luminal side
- highly invaginated baso-lateral side, with many mitochondria |
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name the two types of nephrons
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1. superficial
2. juxtamedullary |
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what is the glomerular endothelium permeable and not permeable to?
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Permeable: water, small solutes (Na, urea, glucose), small proteins
Not permeable: cells |
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which component of the filtration barrier carries the negative charge to repel anionic proteins?
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- all
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which component of the filtration barrier contains the filtration slit?
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- popocytes
- each filtration slit is bridged by a thin diaphragm, which contains poors - podocalycin is a meg charged glycoprotein in podocytes, and are thought to keep the filtration slits open |
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what is neprhin?
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- transmembrane protein that is a major component of the slit diaphragm
- mutations in the nephrin gene in some people with congenital nephrotic syndrome can lead to abnormal or absent slit diaphragms |
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define: nephrotic sydnrome
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- produced by a variety of disorders
- increased permeability of the glomerular capillaries to proteins |
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what is Alport's syndrome?
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- characterized by hematuria
- progressive glomerulonephritis - accounts for 1-2% of the cases of end-stage renal failure |
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define: glomerulonephritis
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- inflammation of the glomerular capillaries
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what is the mech behind Alport syndrome?
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- caused by defects in type IV collagen, a major component of the glomerular basement membrane
- in 85% of Alports patients, the disease is X-linked recessive with mutations in the COL4A5 gene |
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what happens to the glomerular basement membrane in Alport's syndrome?
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- Glomerular BM becomes irregular in thickness and fails as a barrier to RBCs and protein
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what makes up the mesangium?
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- mesangial cells: similar in structure to monocytes
- mesangial matrix |
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describe mesangial cells
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- similar in structure to monocytes
- suppround glomerular capillaries and provide structural support - secrete extracellular matrix - have phagocytic activity - secrete prostglandins and cytokins |
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how do mesangial cells play into immune- complex mediated glomerular disease?
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- BM does nto completely surround glomerular capillaries, and immune complexes can enter the mesangial area without crossing the glomerular BM
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what makes up the juxtaglomerular aparatus?
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- extraglomerular mesangial cells
- macula densa of the TAL - renin-producing granular cells |
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which cells in the kidney produce renin?
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- granular cells of the afferent arteriole
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describe the nerve supply to the kidney
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- no parasympathetic innervation
- the adrenergic fibers release NE, and DA - renin secretion is activated by increased sypathetic activity |
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describe the cels of the renal calyces, pelvis, ureter and urinary bladder
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- lined by transitional epithelium: basal columnar cells, intermediate cuboidal cells, superficial squamous cells
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what is the detrusor muscle?
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- the muscle that surrounds the bladder
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describe the innervation of the bladder and urethra
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- smooth muscle of bladder neck and urethra have a1
-adrenergic receptors - stimulation causes constriction - sacral muscarinic/parasympathetic fibers cause sustained bladder contraction |
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define clearance
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- has dimensions volume/time, and represents a volume of plasma from wich all the substance has been removed and excreted inot the urine per unit of time
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what is inulin?
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- a polymer of fructose that is used to measure GFR
- not produced by body, so given via IV - not reabsorbed, secreted or metabolized - GFR = clearance of inulin |
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why do you use creatinine instead of inulin to approximate GFR?
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- don't have to give it IV
- creatinine is a by-product o skeletal muscle creatine metabolism - however, not a perfect measure of GFR, b/c a small portion is secreted by the organic cation secretory system in the PT |
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define filtration fraction
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FF = GFR/RPF
- on average, 15-20%!! |
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by how much will the GFR be reduced if you have a 50% decline in functioning nephrons?
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- only a 20-30% fall in GFR
- the remaining nephrons compensate |
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what are normal values for GFR in males and females?
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- males: 90-140 ml/min
- females: 80-125 ml/min |
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what is K_f: the ultrafiltration coefficient?
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- product of intrinsic permeability of the glomerular capillary and glomerular surface area available for filtration
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define RBF (eqn)
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RBF = delta P/R
RBF = (aortic pressure - renal venous pressure)/ renal vascular resistance |
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what are the 2 mechanisms for autoregulation to keep the GFR constant thoughout varied blood pressures (90-180mmHg)
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1. myogenic mech: tendency for vascular smooth muscle to contract when stretched
2. tubuloglomerular feedback: NaCl concentration of tubular fluid is sensed by the macula densa of the juxtaglomerular apparatus |
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what is the effector molecule for tubuloglomerular feedback?
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- adenosine constricts the afferent arteriole (dilates in most other vascular beds)
- the macula densa also can release NO for dilation |
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when is autoregulation absent?
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- at blood pressures below 90mmHg
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describe the role of sympathetic nerves on RBF and GFR
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- afferent and efferent arterioles are innervated by sympathetic nerves (a1-adrenergic receptor)
- NE is secreted by sympathetic nerves, and Epi is secreted by the adrenal medulla -> constrict afferent arteriols |
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where is angiotensin II produced?
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- systemically and within the kidney
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what does angiotensin II do to RBF and GFR?
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- decreases both
- constricts the afferent and efferent arteriols |
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describe the different effects of angiotensin II on the afferent and efferent arterioles at low and high concentrations
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- the efferent arteriole is more sensitive to ang II
- at low doses, constriction at the efferent arteriole predominates - at high doses, constriction of both afferent and efferent occur -> fall in GFR and RBF |
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how do ACE inhibitors affect RBF and GFR?
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- ACE inhibitors decrease angiotensin II levels and elevate bradykinin levels -> increase RBF and GFR
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what is the role of prostaglandins on RBF and GFR?
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- no role in healthy people
- in disease state (e.g. hemorrhage), PGI2 and PGE2 are produced in the kidneys and increase RBF without changing GFR - mech: prostaglandins dampen vasoconstrictor effects of the sympathetic nerves and of ang II - prevents severe vasoconstriction and ischemia |
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when do you see abnormal production of NO?
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- in DM and hypertension
- in DM, may contribute to glomerular hyperfiltration and damage of glomerulus |
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when is endotheliun produced?
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- endothelin is a vasoconstrictor secreted by endothelial cells of renal vessels, mesangial cells, and distal tubular cells in response to ang II, bradykinin, Epi and stretch
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what is the role of kallikrein?
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- kallikrein is a proteolytic enzyme make by the kidneys
- kallikrein cleaves circualting kininogen to bradykinin, which is a vasodilator that acts by stimulating the release of NO and prostaglandins |
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what is the role of ANP on GFR and RBF?
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- ANP casues vasodilation of the afferent arteriole and vasoconstriction of the eferent arteriole
- increase in GFR and little change in RBF |
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what is the effect of glucocorticoids on GFR and RBF?
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- increase both
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define: transcellular pathway
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- movement of substance through cells (rebasorption or secretion)
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define: paracellular pathway
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- movement of substance by solvent drag pass through the tight junctions into the lateral intercellular space
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what does the proximal tubule reabsorb?
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- 2/3 of all the water, Na, Cl, K
- all the glucose and amino acids |
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what is the key transporter in the PT?
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- Na, K, ATPase on the basolateral surface of the PT
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how is Na absorption different in the first half of the PT from the second half of the PT?
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1. First half: reabsorbed with HCO3 and other organic molecules (glucose, amino acids, Phosphate_inorganic, lactate)
2. Second half: reabsorbed with Ca (trans and paracellular) - more water than Cl is reabsorbed in the early segment of the PT, so Cl concentration rises as you move down the PT |
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how much of NaCl is transporteed paracellularly and transcellularly in the PT?
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- 2/3 trasncellular
- 1/3 paracellular |
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what is Fanconi's sydnrome?
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- renal disease that is either hereditary or acquired
- impaired ability of the PT to reabsorb amino acids, glucose, and low-molecular-weight proteins - causes increase of the above in urine |
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describe the reabsorption of protein in the PT
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- proteins are degraded by enzymes on the surface of the PT cells
- partially degraded proteins are endocytosed - enzymes digest the proteins and peptides into amino acids in the cell - amino acids exit the cell via the Basolateral membrane and return to the circulation |
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what are the two sources of protein in the urine?
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1. filtration and incomplete reabsorption by the PT
2. synthesis of protein by the TAL - cells in the TAL produce Tamm-Horsfall glycoprotein and secrete the protein into the tubular fluid |
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what is Tamm-Horsfall glycoprotein?
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- a protein that's produced by the TAL
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what does the PT secrete?
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- p-aminohippuric acid (PAH)
- exogenous organic compounds: - penicillin, ibuprofen, indomethacin, naproxen - adefovir (for HIV) |
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what happens to all the organic anions and cations from the plasma entering the kidneys?
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- completely removed either by filtration (hard, if bound to plasma proteins), and secretion
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how do you increase the half-life of penicillin in the circulation?
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- administer PAH.
- all the organic anions compete for the same transporters (since the transporters aren't specific) - you can saturate PAH transport and prolong penicillin in the blood |
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interaction of organic cation drugs in the PT
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- cimetidine (H2 antagonist) is secreted by the organic cation pathway in the PT
- it reduces urinary excretion of procainamide (antiarrhythmic) - administration of both can lead to drug toxicity |
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what do you have to be worried about when you see a patient with both arrhythmia and ulcers?
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- co-administration of cimetidine and procainamide
- can cause toxicity! |
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what does P-glycoprotein do?
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- trasnprots hydrophobic ationic compounds and some drugs: anticancer agents, digoxin, cyclosporin
- have APTase activity - found on apical surface of PT cell - transfer organic compoudns from the cell interior into tubular fluid |
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cimitidine
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- H2 blocker
- treats gastric ulcers |
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what are P-glycoprotein and Mrp2?
|
- multidrug resistance proteins
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name the MDR proteins
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- P-glycoprotein
- Mrp2 |
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what is Mrp2?
|
- MDR associated protein 2
- has APTase activity - found on the apical surface of PT cells - secrete organic compoudns from the cell interior into tubular fluid - trasnprots glutathione-conjugated leukotriene C4 and the glucuronide-conjugated of bilirubin |
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what is Mrp1?
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- found on the basolateral side
- move organic compounds from the blood into the cells of the PT |
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what does Henle's loop do?
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- reabsorb 25% of filtered NaCl, and K
- reabsorb Ca and HCO3- (mainly in the TAL) |
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which part of Henle's Loop is permeable to water?
|
TAL
- NOT the thin descending limb, or the thin ascending limb |
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what is the key transporter in the TAL?
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- Na, K-ATPase on the basolateral membrane
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how does the voltage across the TAL help in reabsorption of cations?
|
- tubular fluid is positively charged relative to blood
1. increased salt trasnprot by the TAL increases the magnitude of the postive charge in the lumen 2. this voltage is the driving force for Na, K and Ca across the PARACELLULAR pathway |
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describe the ratio of transcellular to pericellular trasnport in the TAL
|
- 50-50
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what is Bartter's syndrome?
|
- set of autosomal recessive genetic disorders characterized by hypokalemia, metabolic alkalosis, and hyperaldosteronism
- mutation in the gene for the Na, K, 2Cl cotrasnporter, the apical K channel, or the basolateral Cl chanel in the TAL - decreased NaCl and K absorption in the TAL -> hypokalemia and decreases the effective circulating volume -> secretion of aldosterone |
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how do loop diuretics work?
|
- e.g. furosemide
- inhibit the Na-K-2Cl symporter - inhibts NaCl reabsorption by the TAL -> increase NaCl urinary secretion - also inhibits K and Ca reabsorption by reducing the LUMEN_POSITIVE VOLTAGE (needed for paracellular absorption of these ions) -> increased urinary K and Ca secretion - abolishes corticomedullary gradient |
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what does the distal tubule and CD do?
|
- reabsorb 7% of filtered NaCl
- secrete variable amounts of K and H - reabsorb variable amount of water (8-17%) |
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Describe the early distal tubule
|
- reabsorbs Na, Cl and Ca
- impermeable to water |
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how do thiazide diuretics work?
|
- inhibit the NaCl symporter in the distal tubule
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where are intercalated and principal cells found?
|
- late distal tubule
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what do principal cells do?
|
- reabsorb Na and water
- secrete K |
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what do intercolated cells do?
|
- either secrete H (reabsorb HCO3) or secrete HCo3-
- necessary for acid-base balance - reabsorb K |
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what is Liddle's sydrome?
|
- rare genetic disorder characterized by increase in ECF volume -> increase in BP
- caused by mutations of the genes that encode the beta or gamma subunit of ENaC -> cause Na channels to be overactive -> hypertension |
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what is Pseudohypoaldosteronism type I (PHA1)?
|
- uncommon and inherited disorder
- increase in Na excretion - reduciton in ECF volume - hypotension - mutation in gamma subunit of ENaC -> inactivate channel |
