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87 Cards in this Set
- Front
- Back
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Prerenal azotemia
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Hypoperfusion of Kidneys
decreased GFR NO parenchymal damage BUN/Cr ratio > 15 |
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When does azotemia become uremia
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progression to clinical manifestations
systemic biochemical abormalities failure of renal excretory functions |
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Layers of glomerulus/bowman's capsule from outside to inside
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From outside to inside
1) Parietal Epithelim 2) Urinary Space 3) Podocytes (visceral epithelium) 4) GBM-- lamina rara externa Lamina densa Lamina rara interna 5) Fenestrate endothelium *within this capillary network are interspersed mesangial cells (supports glomerular tuft) |
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GBM properties
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Collagen Type IV
Laminin, polyanionic proteoglycans, fibronectin, glycoproteins Heparan Sulfate (negative charge) Outside to inside--Lamina rara externa (faces podocytes) LaminaDensa Lamina rara interna |
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Mesangial cells
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support glomerular tuft
lie between capillaries mesenchymal origin are contractile capable of proliferation can lay down both matrix and collagen secrete mediators (cytokines) |
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Podocytes-- major roles
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1) Controls filtration barrier
2) GBM synthesis |
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Nephrin
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transmembrane glycoprotein that comprises major part of the slit diaphragms between adjacent podocyte pedicles
Bind adjacent pedicles nephrine via disulfide bridges Intracellular part of nephrin (sticking into podocyte) interacts with cytoskeletal and signaling proteins one of these associated proteins is PODOCIN, which is also important in maintaining selective permeability of barrier |
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Immune complex glomerular disease- example of endogenous
exogenous antigen |
Neither are of glomerular origin
Endogenous antigen causing type 3 hypersensitivity- ex) SLE Exogenous Antigen- ex) Bacterial (streptococcal), viral |
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Granular Immunoflouresence in Glomerular disease
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1) Immune Complex Deposition
2) antibodies reacting with previously planted nonglomerular antigens--includes DNA, bacterial products, protein aggregations, immune complexes... |
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Linear Immunoflouresence in Glomerular Disease
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1) anti-GBM
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Hypoperfusion of Kidneys
decreased GFR NO parenchymal damage BUN/Cr ratio > 15 |
Prerenal azotemia
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progression to clinical manifestations
systemic biochemical abormalities failure of renal excretory functions |
When does azotemia become uremia
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support glomerular tuft
lie between capillaries mesenchymal origin are contractile capable of proliferation can lay down both matrix and collagen secrete mediators (cytokines) |
Mesangial Cells
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Anti-GBM disease
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usually goodpasture's
basement membrane antigen responsible for this is part of noncollagenous domain of the a3 chain of collagen 4 can also react with alveolar BM's can cause rapidly progressing crescenteric glomerulonephritis |
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How localization of antigen in glomerulus affects response
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Localization of ag, ab, ICs determine injury
--Proximal zones of GBM (endothelium, subendothelium)-- inflammatory --Distal zones of GBM (epithelium, subepithelium)--non-inflammatory (ex- membranous nephropathy) |
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antibody-initiated glomerular injury mediated via complement-leukocytes
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Complement activated
--> C5a generation recruitment of monocytes and neutrophils Neutros release proteases--> GBM degradation Neutrophils ---> ROS Arachadonic acid metabolites --> reduce GFR |
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Complement dependent but not neutrophil dependent glomerular injury
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C5-C9 ---> MAC
Direct damage & MAC upregulates ---> TGF-B production by podocytes--> ECM synthesis |
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Maladaptive changes in intact glomeruli
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Happen after compensatory changes when theres nephron loss
Remaining nephrons make these compensatory changes, which ultimately maladaptive: Hypertrophy to maintain Renal fnxn, increases in single Nephron GFR, blood flow ultimately causes glomerulosclerosis, leading to further endothelial and epithelial injury: Glomerular permeability to proteins Protein/Lipid accumulation in mesangial matrix |
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Benign Nephrosclerosis- advanced cases
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Advanced cases-- glomerular tufts sclerosed
Tubular atrophy Interstitial fibrosis Lymphocytic infiltrate Fibroelastic hyperplasia (medial thickening and in larger vessels, like interlobar and arcuate arteries) |
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Malignant Htn and Malignant Nephrosclerosis
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~5% of Htn cases. Defined by Dias > 120 mm Hg, papilledema, etc.
Most symptoms due to increased intracranial pressures At onset- proteinuria, maybe hematuria, no renal problems initially but eventually failure 90% of deaths- Uremia 10% CVA or Cardiac Pathogenesis: 1) Long standing Benign Htn injures arteriolar walls 2) Vessel permeability to fibrinogen + endothelial injury = Platelet activation 3) --> Fibrinoid Necrosis (arterioles and small arteries) --> intravascular thrombosis? 4) Mitogenic Factors (PDGF) --> Intimal SMC hyperplasia --> hyperplastic arteriosclerosis Hyperplastic Arteriosclerosis -- 1) narrow lumen 2) kidneys ischemic 3) renal afferent arterioles release Renin --> activate RAS 4) self perpetuating, intrarenal vasoconstriction, more renin release 5) A2 causing aldosterone release on top of this Kidneys shrunken or normal in size Pinpoint petechial hemorrhages ("flea-bitten") Onion-skinning (interolobular arteries and larger arterioles) (hyperplastic arteriosclerosis) |
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Hemolytic Uremic Syndrome (HUS)
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Endothelial injury and activation --> intravascular (micriangiopathic) thrombosis
Childhood HUS- 75% of cases from E.Coli that produces Shiga-Toxin Toxin targets renal glomerular cells, affecting endothelium: Increased leukocyte adhesion Inc. Endothelin production Dec. NO production Endothelial Damage & Vasoconstriction Toxin also enters cells and causes direct cell death 10% of cases of Childhoos HUS not from Shiga Many of these come from mutational inactivation of Factor H, which normally regulates complement activation --> uncontrolled complement activation Morphologically--Widening of subendothelial space in glomerular capillaries Duplication/Splitting of GBM Lysis of Mesangial cells Clinical- Sudden Onset Childhood- managed properly, good chance of recovery, but longterm nearly 25% get renal failure |
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Endothelial injury and activation --> intravascular (micriangiopathic) thrombosis
Childhood HUS- 75% of cases from E.Coli that produces Shiga-Toxin Toxin targets renal glomerular cells, affecting endothelium: Increased leukocyte adhesion Inc. Endothelin production Dec. NO production Endothelial Damage & Vasoconstriction Toxin also enters cells and causes direct cell death 10% of cases of Childhoos HUS not from Shiga Many of these come from mutational inactivation of Factor H, which normally regulates complement activation --> uncontrolled complement activation Morphologically--Widening of subendothelial space in glomerular capillaries Duplication/Splitting of GBM Lysis of Mesangial cells Clinical- Sudden Onset Childhood- managed properly, good chance of recovery, but longterm nearly 25% get renal failure |
Hemolytic Uremic Syndrome (HUS)
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~5% of Htn cases. Defined by Dias > 120 mm Hg, papilledema, etc.
Most symptoms due to increased intracraneal pressures At onset- proteinuria, maybe hematuria, no renal problems initially but eventually failure 90% of deaths- Uremia 10% CVA or Cardiac Pathogenesis: 1) Long standing Benign Htn injures arteriolar walls 2) Vessel permeability to fibrinogen + endothelial injury = Platelet activation 3) --> Fibrinoid Necrosis (arterioles and small arteries) --> intravascular thrombosis? 4) Mitogenic Factors (PDGF) --> Intimal SMC hyperplasia --> hyperplastic arteriosclerosis Hyperplastic Arteriosclerosis -- 1) narrow lumen 2) kidneys ischemic 3) renal afferent arterioles release Renin --> activate RAS 4) self perpetuating, intrarenal vasoconstriction, more renin release 5) A2 causing aldosterone release on top of this Kidneys shrunken or normal in size Pinpoint petechial hemorrhages ("flea-bitten") Onion-skinning (interolobular arteries and larger arterioles) (hyperplastic arteriosclerosis) |
Malignant Htn and Malignant Nephrosclerosis
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Underlying defect in hereditary renal cystic diseases
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Cilia-centrosome complex of tubular epithelial cells have defect, interfering with fluid absorption and cellular maturation
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Simple Renal Cysts
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Translucent, filled w/ clear fluid
Membrane composed of simple cuboidal epithelium (which may be atrophic) Cysts confined to cortex Common, no clinical significance, just need to distinguish from tumors In contrast to tumors, cysts have smooth contours, Avascular, fluid signals (not solid) on ultrasound |
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Translucent, filled w/ clear fluid
Membrane composed of simple cuboidal epithelium (which may be atrophic) Cysts confined to cortex Common, no clinical significance, just need to distinguish from tumors In contrast to tumors, cysts have smooth contours, Avascular, fluid signals (not solid) on ultrasound |
Simple Renal Cysts
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Dialysis acquired renal cysts
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present in both cortex and medulla
may bleed ---> hematuria Renal adenomas (or even adenocarcinomas) may arise from them |
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present in both cortex and medulla
may bleed ---> hematuria Renal adenomas (or even adenocarcinomas) may arise from them |
Dialysis acquired renal cysts
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Adult Polycystic Disease
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Autosomal dominant
PKD 1 (Chr 16) --encodes cell membrane associated protein (mostly extracellular) Polycystin-1 involved in cell-cell/cell-matrix adhesion resultant defects lead to cyst formation polycystins localized in tubular cilia Similar to a tumor suppressor gene in that a second somatic hit is required cysts start forming in adolesence, but symptoms not until 5th decade PKD 2- chr4- polycystin 2-- calcium membrane channel PKD2 patients have slower progression Polycystin 1 &2 believed to act together in heterodimer Kidneys become enormous, palpable, intervening parenchyma obliterated Cysts filled with fluid (can be hemorrhagic) Cysts can be at any level of the nephron Pt presents with flank pain, heavy dragging sensation, intermittent hematuria Complications from Htn (in 75% of pt's), UTI Circle of Willis aneurysms in 10 to 30%....many of these patients develop arachnoid hemorrhage |
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Autosomal dominant
PKD 1 (Chr 16) --encodes cell membrane associated protein (mostly extracellular) Polycystin-1 involved in cell-cell/cell-matrix adhesion resultant defects lead to cyst formation polycystins localized in tubular cilia Similar to a tumor suppressor gene in that a second somatic hit is required cysts start forming in adolesence, but symptoms not until 5th decade PKD 2- chr4- polycystin 2-- calcium membrane channel PKD2 patients have slower progression Polycystin 1 &2 believed to act together in heterodimer Kidneys become enormous, palpable, intervening parenchyma obliterated Cysts filled with fluid (can be hemorrhagic) Cysts can be at any level of the nephron Pt presents with flank pain, heavy dragging sensation, intermittent hematuria Complications from Htn (in 75% of pt's), UTI Circle of Willis aneurysms in 10 to 30%....many of these patients develop arachnoid hemorrhage |
Adult Polycystic Disease
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Childhood Polycystic Disease
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Autosomal recessive
Subcategories based on time of presentation and hepatic involvement PKHD1 gene-- membrane receptor Fibrocystin (involved in tubular epithelial cilia) Cysts lined by cuboidal Cysts origin is collecting tubules Disease is bilateral Cysts in liver, bile ducts Rare to survive beyond perinatal/neonatal forms Pt's who survive infancy get liver cirrhosis (hepatic fibrosis) |
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Autosomal recessive
Subcategories based on time of presentation and hepatic involvement PKHD1 gene-- membrane receptor Fibrocystin (involved in tubular epithelial cilia) Cysts lined by cuboidal Cysts origin is collecting tubules Disease is bilateral Cysts in liver, bile ducts Rare to survive beyond perinatal/neonatal forms Pt's who survive infancy get liver cirrhosis (hepatic fibrosis) |
Childhood Polycystic Disease
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Medullary Cystic Disease
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Most common (medullary sponge kidney)- harmless
Nephronophthisis-medullary cystic disease- harmful Four variants (e/ w/ different gene)- infantile, juvenile, adolescent, adult usually begins in childhoos, juvenile form is hte most common 15-20% with juvenile nephronophthisis have extrarenal problems: RETINA, mental, cerebellar, liver Most common GENETIC cause of end-stage renal disease in young Nephrocystins are components of epithelial cell cilia The two genes that are autosomal dominant are associated with adult disease Morphology- small contracted kidneys small cysts lined by flattened/cuboidal epithelium at CORTICO-MEDULLARY junction Clinical- Polyuria, polydipsia (diminished tubular function), progression over 5-10 years trouble with diagnosing-- sometimes too small for imaging hard to get it on biopsy Need to keep in mind FAMILY HISTORY |
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Most common (medullary sponge kidney)- harmless
Nephronophthisis-medullary cystic disease- harmful Four variants (e/ w/ different gene)- infantile, juvenile, adolescent, adult usually begins in childhoos, juvenile form is hte most common 15-20% with juvenile nephronophthisis have extrarenal problems: RETINA, mental, cerebellar, liver Most common GENETIC cause of end-stage renal disease in young Nephrocystins are components of epithelial cell cilia The two genes that are autosomal dominant are associated with adult disease Morphology- small contracted kidneys small cysts lined by flattened/cuboidal epithelium at CORTICO-MEDULLARY junction Clinical- Polyuria, polydipsia (diminished tubular function), progression over 5-10 years trouble with diagnosing-- sometimes too small for imaging hard to get it on biopsy Need to keep in mind FAMILY HISTORY |
Medullary Cystic Disease
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Nephrotic Syndrome
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1) massive proteinuria (> 3.5 gm/day)
2) hypoalbuminemia 3) edema (drop in oncotic pressure and primary salt/water retention + aldosterone) 4)hyperlipidemia/lipiduria At onset, very little azotemia, hematuria, Htn |
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1) massive proteinuria (> 3.5 gm/day)
2) hypoalbuminemia 3) edema (drop in oncotic pressure and primary salt/water retention + aldosterone) 4)hyperlipidemia/lipiduria At onset, very little azotemia, hematuria, Htn |
Nephrotic Syndrome
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How Nephrotic Syndrome Causes vary by age
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Children (1 to 7)-- primary kidney lesion (MCD)
Adults-- manifestations of a disease (diabetes, amyloidosis, SLE) |
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Most important primary glomerular lesions that lead to nephrotic syndrome
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FSGS (adults)
MCD (Kids) Other primary lesions-- membranous nephropathy membranoproliferative GN |
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Minimal Change Disease
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Lipoid Nephrosis"
NONIMMUNE (NO antibody deposits) children glomeruli look normal by light microscope diffuse podocyte effacement by electron microscope unclear pathogenesis--> T-cell factor damaging podocytes?? PCT cells have protein and lipid droplets (tubular reabsorption of lipoproteins) Usually corticosteroids (esp. in kids) cause podocyte changes to reverse, and proteinuria remits Clinical-- insidious development no Htn selective (albumin) proteinuria |
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"Lipoid Nephrosis"
NONIMMUNE (NO antibody deposits) children glomeruli look normal by light microscope diffuse podocyte effacement by electron microscope unclear pathogenesis--> T-cell factor damaging podocytes?? PCT cells have protein and lipid droplets (tubular reabsorption of lipoproteins) Usually corticosteroids (esp. in kids) cause podocyte changes to reverse, and proteinuria remits Clinical-- insidious development no Htn selective (albumin) proteinuria |
Minimal Change Disease
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FSGS
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Often associated with nephrotic syndrome
NONIMMUNE Can be in association with HIV, heroin use or Secondary from other forms of Glomerulonephritis or Maladaption after nephron loss or Inherited or Primary (20-30%) (pathogenesis unknown-- but podocyte injury is initiating event) **Hematuria **Htn **NONselective proteinuria 50% ---> endstage renal failure within 10 years Hyaline Deposition (trapped protein and lipids in injury focus where sclerosis occurs) IGM and complement often seen in lesion Increased mesangial matrix, obliterated capillary lumens Podocyte effacement Eventually global glomeruli sclerosis --> tubular atrophy, interstitial fibrosis can lead to collapsing gomerulopathy Initially only juxtamedullary (still cortex) glomeruli, then goes outward Poor response to steroids |
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Often associated with nephrotic syndrome
NONIMMUNE Can be in association with HIV, heroin use or Secondary from other forms of Glomerulonephritis or Maladaption after nephron loss or Inherited or Primary (20-30%) (pathogenesis unknown-- but podocyte injury is initiating event) **Hematuria **Htn **NONselective proteinuria 50% ---> endstage renal failure within 10 years Hyaline Deposition (trapped protein and lipids in injury focus where sclerosis occurs) IGM and complement often seen in lesion Increased mesangial matrix, obliterated capillary lumens Podocyte effacement Eventually global glomeruli sclerosis --> tubular atrophy, interstitial fibrosis can lead to collapsing gomerulopathy Initially only juxtamedullary (still cortex) glomeruli, then goes outward Poor response to steroids |
FSGS
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Membranous Glomerulopathy
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Nephrotic
slowly progressive *response against an unknown renal antigen usually SUBEPITHELIAL Ig containing deposits along GBM so little inflammation advanced cases --> diffuse capillary-wall thickening Idiopathic (85%) or secondary to other insults (incl. drugs like catopril, NSAIDs) **Form of chronic IMMUNE COMPLEX nephritis most idiopathic forms induced by antiboies to in-situ endogenous/glomerular antigens Damage isn't from monocytes, neutros, rather from complement MAC which also activates mesangial cells and podocytes --> damages capillary walls Morphologically-----Diffuse GBM thickening, subepithelial deposits (SPIKE AND DOME) Granular immunoflouresence Insidious development NONSELECTIVE proteinuria not responsive to steroids variable and indolent course, about 40% suffer chronic disease |
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Nephrotic
slowly progressive *response against an unknown renal antigen usually SUBEPITHELIAL Ig containing deposits along GBM so little inflammation advanced cases --> diffuse capillary-wall thickening Idiopathic (85%) or secondary to other insults (incl. drugs like catopril, NSAIDs) **Form of chronic IMMUNE COMPLEX nephritis most idiopathic forms induced by antiboies to in-situ endogenous/glomerular antigens Damage isn't from monocytes, neutros, rather from complement MAC which also activates mesangial cells and podocytes --> damages capillary walls Morphologically-----Diffuse GBM thickening, subepithelial deposits (SPIKE AND DOME) Granular immunoflouresence Insidious development NONSELECTIVE proteinuria not responsive to steroids variable and indolent course, about 40% suffer chronic disease |
Membranous Glomerulopathy
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Nephrotic (usually), can be nephritic, or both
GBM and mesangium alterations Proliferation of glomerular cells Divided into Type I and Type 2 Type 1--circulating immune complexes Type 2-excessive complement activation Poor Prognosis (especially Type 2--"dense-deposit disease") |
Membranoproliferative Glomerulonephritis
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Membranoproliferative Glomerulonephritis
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Nephrotic (usually), can be nephritic, or both
GBM and mesangium alterations Proliferation of glomerular cells Divided into Type I and Type 2 Type 1--circulating immune complexes Type 2-excessive complement activation Poor Prognosis (especially Type 2--"dense-deposit disease") |
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MPGN caused by circulating immune complexes (unknown antigen or in association with Hepatitis, SLE, infections)
Discrete subendothelial electron-dense deposits, indicating Immunen complex |
MPGN Type 1
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MPGN Type 1
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MPGN caused by circulating immune complexes (unknown antigen or in association with Hepatitis, SLE, infections)
Discrete subendothelial electron-dense deposits, indicating Immunen complex |
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MPGN Type 2
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MPGN caused by excessive complement activation due to an autoantibody against C3 convertase
(this antibody is called C3 nephritic factor--it stabiliizes the enzyme, leading to uncontrolled C3 activation (or mutation in plasma Factor H, which results in excessive complement activation) Hypocomplementemia in this (reduced synthesis of C3 by liver) Lamina Densea and subendothelial GBM soace have deposition of something --> "dense-deposit disease" C3 present in GBM and mesangium (mesangial rings), IgG is ABSENT |
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MPGN caused by excessive complement activation due to an autoantibody against C3 convertase
(this antibody is called C3 nephritic factor--it stabiliizes the enzyme, leading to uncontrolled C3 activation (or mutation in plasma Factor H, which results in excessive complement activation) Hypocomplementemia in this (reduced synthesis of C3 by liver) Lamina Densea and subendothelial GBM soace have deposition of something --> "dense-deposit disease" C3 present in GBM and mesangium (mesangial rings), IgG is ABSENT |
MPGN Type 2
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Nephritic Syndrome--general features
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Hematuria (RBC casts)
Some Oliguria/azotemia Some Proteinuria, some edema **Proliferation of cells within glomeruli ---> leukocyte infiltration --> injures capillary walls --> eventually dec. GFR (and fluid retention) Htn Can be secondary (SLE) or primary (postinfectious GN) |
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Hematuria (RBC casts)
Some Oliguria/azotemia Some Proteinuria, some edema **Proliferation of cells within glomeruli ---> leukocyte infiltration --> injures capillary walls --> eventually dec. GFR (and fluid retention) Htn Can be secondary (SLE) or primary (postinfectious GN) |
Nephritic Syndrome--general features
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Acute postinfectious GN
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nephritic
usually poststreptococcal; other exogenous antigen or endogenous antigen are possible Endogenous antigen more common in membranous nephropathy immune complex deposition (so you see hypocomplementemia) --> causes diffuse proliferation and leukocyte infiltration usually "subepithelial hump" granular IgG and complement deposits on GBM Uniformly increased cellularity (thus "diffuse" from endothelial and mesangial proliferation **Child, 1 to 4 weeks after Group A Strep Infection (B-hemolytic) (usually initial infection is pharyngeal or skin) **Onset of kidney disease- abrupt, slight fever, nausea, nephritic syndrome smoky brown hematuria low serum complement Recovery in most children, not as much so in adults Can progress to crescenteric |
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nephritic
usually poststreptococcal; other exogenous antigen or endogenous antigen are possible Endogenous antigen more common in membranous nephropathy immune complex deposition (so you see hypocomplementemia) --> causes diffuse proliferation and leukocyte infiltration usually "subepithelial hump" granular IgG and complement deposits on GBM Uniformly increased cellularity (thus "diffuse" from endothelial and mesangial proliferation **Child, 1 to 4 weeks after Group A Strep Infection (B-hemolytic) (usually initial infection is pharyngeal or skin) **Onset of kidney disease- abrupt, slight fever, nausea, nephritic syndrome smoky brown hematuria low serum complement Recovery in most children, not as much so in adults Can progress to crescenteric |
Acute postinfectious GN
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Berger Disease
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"IgA Nephropathy"
Children/young adults Upper resp. tract infection then 1-2 days later: gross hematuria RECURRING disease Loin pain, most common glomerular disease out there *IgA deposition in mesangium, lesions confined to kidney (if systemic then it is Henoch Schonlein purpura) Abnormal IgA production and clearance HLA link Abnormality in IgA glycosylation favoring mesangial deposition can lead to activation of alternative complement path **Associated with celiac disease and liver disease (secondary IgA nephropathy due to defective hepatobiliary clearance) Morphologically- very varying patterns Clinical- very variable, recurs every few months, slow progression to CRF over 20 years in 25-50% |
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"IgA Nephropathy"
Children/young adults Upper resp. tract infection then 1-2 days later: gross hematuria RECURRING disease Loin pain, most common glomerular disease out there *IgA deposition in mesangium, lesions confined to kidney (if systemic then it is Henoch Schonlein purpura) Abnormal IgA production and clearance HLA link Abnormality in IgA glycosylation favoring mesangial deposition can lead to activation of alternative complement path **Associated with celiac disease and liver disease (secondary IgA nephropathy due to defective hepatobiliary clearance) Morphologically- very varying patterns Clinical- very variable, recurs every few months, slow progression to CRF over 20 years in 25-50% |
Berger Disease
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Hereditary Nephritis i.e. Alport
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Type IV collagen defect that effects lens, cochlea, glomerulus
Mutation in one of the alpha chains most common is x-linked mutation of a5 collagen secondary sclerosis occurs late in the disease, interstitial cells can become foamy in appearance Pt's present at 5-20 years old, renal failure about 20-50 years old |
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Type IV collagen defect that effects lens, cochlea, glomerulus
Mutation in one of the alpha chains most common is x-linked mutation of a5 collagen secondary sclerosis occurs late in the disease, interstitial cells can become foamy in appearance Pt's present at 5-20 years old, renal failure about 20-50 years old |
Hereditary Nephritis i.e. Alport
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Crescenteric Glomerulonephritis-- another name for it
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Rapidly Progressive Glomerulonephritis
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Rapidly Progressive Glomerulonephritis--another name for it
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Crescenteric Glomerulonephritis
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Crescenteric Glomerulonephritis
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rapid and progressive loss of renal function
Immunologically mediated death within weeks-months Histologically- Crescents these are from proliferation of parietal epithelial cells (Bowman's capsule) (from injury/infiltration of monocytes/macros) Three Types- Type 1- Anti-GBM (linear IgG deposits) can plasmapherese these patients Renal Petechial Hemorrhages Exudation of plasma proteins (fibrin) into Bowman's Crescents eventually obliterate Bowman's space....can undergo scarring Type 2-- Immune Complex-mediated (post-strep GN, SLE, IgA) Plasmapheresis is ineffective Type 3-- Pauci-Immune ANCAs (can have concomitant Wegener's or microscopic polyangitis) Clinical- Similar to nephritic (hematuria) except oliguria and azotemia are more pronounced, as can proteinuria |
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rapid and progressive loss of renal function
Immunologically mediated death within weeks-months Histologically- Crescents these are from proliferation of parietal epithelial cells (Bowman's capsule) (from injury/infiltration of monocytes/macros) Three Types- Type 1- Anti-GBM (linear IgG deposits) can plasmapherese these patients Renal Petechial Hemorrhages Exudation of plasma proteins (fibrin) into Bowman's Crescents eventually obliterate Bowman's space....can undergo scarring Type 2-- Immune Complex-mediated (post-strep GN, SLE, IgA) Plasmapheresis is ineffective Type 3-- Pauci-Immune ANCAs (can have concomitant Wegener's or microscopic polyangitis) Clinical- Similar to nephritic (hematuria) except oliguria and azotemia are more pronounced, as can proteinuria |
Crescenteric Glomerulonephritis
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Chronic Glomerulonephritis
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glomerular changes so far advanced that you can't always tell the original cause
Usually first noted in young/middle-aged SYMMETRICALLY contracted kidneys Surfaces are red-brown, granular Advanced scarring of glomeruli Interstitial fibrosis (and atrophy of cortical tubules) with Lymphocytic infiltrate Loss of some peritubular capillaries Htn --> thickened medium and small arteries with narrowed lumen Clinical- insidious as glomeruli become obliterated, avenue for protein loss is closed and nephrotic syndrome becomes less severe **Hypertension!! |
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Tubuluinterstitial Nephritis
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Inflammatory
**Primarily involves interstitium & tubules (not glomeruli!!) glomerulus can be affected late in the course of disease When it's caused by bacterial infection, usually involves renal pelvis thus pyelonephritis "Interstitial Nephritis" reserved for cases that are nonbacterial in origin can be acute or chronic |
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Acute Pyelonephritis
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bacterial infection, great majority originate from lower urinary tract
**can be hematogenous spread, but not as common as UTI spread can be from septicemia, infective endocarditis inflammation of renal pelvis Usually is E. Coli (enteric G neg, because of proximity to rectum) when it's other bacteria, usually associated with recurrent infections Pathogenesis -- (1) adhesion of bacteria to mucosal surfaces (2) colonization of distal urethra (3) must move against flow of urine (so any obstruction, urethral instrumentation helps) Normally, antimicrobial properties in bladder mucosa, and flushing action of urine prevent ascension Occurs in young children, then mostly female until age 40, then even with males (BPH) Diabetes increases susceptibility (neurogenic) **Vesicoureteral incompetence is an important predisposing factor (can be a congenital defect) Flaccid Bladder after Spinal cord injury Suppurative necrosis/abcess within renal parenchyma early stages limited to interstitial, but later abscesses rupture into tubules WBC casts when obstruction prominent and pus cannot drain, pus fills pelvis, etc. ----> pyonephrosis Infrequent form---papillary necrosis (esp. among diabetics, analgesix abusers--> yellow necrosis os apical 2/3 of pyramids) Pregnancy (4 to 6% prevalence of bacteriuria, 30% of these can get infection) Clinical-- pain at CVA, systemic infection (fever), bladder irritation Disease usually self-limited, symptomatic < 1 week |
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Scarring involving the pelvis, calyces, or both leading to papillary blunting and marked calyceal deformities. Can be detected with radioactive technetium, does not necessarily have bacteriuria
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Chronic Pyelonephritis
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Chronic Pyelonephritis
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Scarring involving the pelvis, calyces, or both leading to papillary blunting and marked calyceal deformities. Can be detected with radioactive technetium, does not necessarily have bacteriuria
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Acute drug-induced interstitial nephritis
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Usually from synthetic penicillins, antibiotics, diuretics, NSAIDs
Hypersensitivity Latent Period Eosinophilia Rash Not dose-related IgE in serum (Type I hypersensitivity) Mononuclear/granuloma infiltrate Positive Skin tests to drugs --> Type IV Hypersensitivity ----Drugs act as haptens, secreted by tubules and covalently bind to component o tubular cells and become immunogenic Interstitial Edema **special for NSAIDs-- podocyte effacement (MCD-like) Clinical- starts 15 days after exposure variable renal abnormalities |
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Renal Papillary Necrosis (appear yellowish-brown)
Aspirin (inhibits prostaglandin synthesis) Acetaminophen (covalent binding, oxidative damage) **pre-existing renal disease seems to be a necessary precursor SECONDARY interstitial nephritis PAS-positive basement membrane thickening 1) Chronic Renal Failure 2) Htn 3) Anemia 4) Increased incidence of transitional-cell carcinoma in survivors |
Analgesic Nephropathy
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Analgesic Nephropathy
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Renal Papillary Necrosis (appear yellowish-brown)
Aspirin (inhibits prostaglandin synthesis) Acetaminophen (covalent binding, oxidative damage) **pre-existing renal disease seems to be a necessary precursor SECONDARY interstitial nephritis PAS-positive basement membrane thickening 1) Chronic Renal Failure 2) Htn 3) Anemia 4) Increased incidence of transitional-cell carcinoma in survivors |
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Most common cause of acute renal failure
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acute tubular necrosis (reversible)
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Ischemic Acute Tubular Necrosis
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Period of inadequate blood flow to peripheral organs, like in hypotension/shock
Ischemic tubular cells express chemokines, cytokines, adhesion molecules that recruit/immobilize leukocytes Necrosis of short segments of tubules, mostly in straight part of PT, ThAL Protein casts in Distal tubules and collecting ducts (Tam-Horse protein secreted by tubular epithelium, Hb, myoglobin) |
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Period of inadequate blood flow to peripheral organs, like in hypotension/shock
Ischemic tubular cells express chemokines, cytokines, adhesion molecules that recruit/immobilize leukocytes Necrosis of short segments of tubules, mostly in straight part of PT, ThAL Protein casts in Distal tubules and collecting ducts (Tam-Horse protein secreted by tubular epithelium, Hb, myoglobin) |
Ischemic Acute Tubular Necrosis
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Nephrotoxic Acute Tubular Necrosis
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poisons-- heavy metals
organic solvents gentamicin (and other antibiotics) contrast agents Necrosis most prominent in proximal tubule Tubular basement membranes are generally spared |
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poisons-- heavy metals
organic solvents gentamicin (and other antibiotics) contrast agents Necrosis most prominent in proximal tubule Tubular basement membranes are generally spared |
Nephrotoxic ATN
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Pathogenesis of acute tubular necrosis
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Ischemic or toxic in nature
reversible tubular epithelial cells are sensitive to anoxia/toxins because: electrically charged surface for fluid reabsorption Loss of cell polarity occurs--> redistribution of membrane proteins (Na/K ATPase) from basolateral to apical membrane --> decreased Na+ reabsorption --> inc. Na+ at distal tubule --> this activated the TGF mechanism --> contributes to intrarenal vasoconstriction Redistribution of integrins that anchor tubular cells to underlying basement membranes causes shedding of tubular cells into the urine, tubular debris can block urine outflow ---> dec. GFR Fluid from damaged tubules could leak into interstitium --> inc. interstitial pressure --> collapse of tubules Reduced GFR and reduced O2 delivery ---> vasoconstriction mediated by sublethal endothelial injury (inc. endothelin, dec. PGs and NO) Biopsy can reveal a variety of tubular injuries at different stages |
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If patient survives ATN for a week
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epithelial regeneration in the form of low cuboidal epithelial covering, mitotic activity
Except where basement membrane destroyed, regeneration is total and complete |
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Clinical Course of ATN
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INITIATION- ~36 hrs, slight decline in urine output (Transient dec. in renal blood flow), rising Cr
MAINTENANCE- begins 2nd-6th day marked oliguria, as long as 3 weeks clinical signs of uremia, fluid overload with dialysis, patients survive RECOVERY-- Steady increase in urine volume electrolyte imbalances persist **vulnerability to infection (1/4 of ATN deaths occur during RECOVERY) |
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INITIATION- ~36 hrs, slight decline in urine output (Transient dec. in renal blood flow), rising Cr
MAINTENANCE- begins 2nd-6th day marked oliguria, as long as 3 weeks clinical signs of uremia, fluid overload with dialysis, patients survive RECOVERY-- Steady increase in urine volume electrolyte imbalances persist **vulnerability to infection (1/4 of ATN deaths occur during RECOVERY) |
Clinical Course of ATN
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What are most renal stones comprised of
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80% are composed of either calcium oxalate or calcium oxalate mixed with calcium phosphate
10% of MgNH4PO4 6-9% are Uric acid or cystine stones All of these stones have about 2% mucoprotein by weight |
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Causes of kidney stones in general
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increased URINE concentration of the stone's constituents, exceed their solubility in urine (supersaturation)
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Calcium Stones
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half of these patients have hypercalciuria that is NOT associated with hypercalcemia
Could be from increased GI absorption (absorbtive calciuria) Primary renal defect of calcium reabsorption (renal hypercalciuria) Uric acid could favor calcium stone formation |
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Urine pH and the types of renal stones
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alkaline urine favors Magnesium Ammonium Phosphate stones and calcium phosphate stones
acidic urine favors cystine stones, uric stones |
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Magnesium Ammonium Phosphate Stones
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"struvite"
people with persistently alkaline urine (due to UTIs) especially from proteus (urea-splitting) and Staph |
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Lack of substances that normally inhibit mineral precipitations in kidney stones
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normally inhibitors of crystal formation in urine include Tam-Horse protein, osteoponton, pyrophosphate, mucopolysaccharides, nephrocalcin (glycoprotein). This hypothesis, however, not definitively proven
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dilation of renal pelvis/calyces ---> atrophy of parenchyma caused by obstruction of outflow of urine
Causes--congenital causes of obstruction, Acquired causes of obstruction (including neurogenic, pregnancy) Even with complete obstruction, glomerular giltration persists and the filtrate subsequently diffuses back into the renal interstitium and is returned via lymphatics and veins. Unusually high pressure transmitted back through collecting ducts, can compress renal vasculature, one effect includes VENOUS STASIS, only later does glomerular filtration start to diminish. Irreversible damage occurs at about 3 weeks of complete obstruction, 3 months with incomplete obstruction. Massively Enlarged kidney Renal parenchyma compressed and atrophied (if this is a chronic proccess) Paradoxically, incomplete bilateral obstruction causes polyuria rather than oliguria at first. Unilateral hydronephrosis may remain silent for a long time |
Hydronephrosis
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Hydronephrosis
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dilation of renal pelvis/calyces ---> atrophy of parenchyma caused by obstruction of outflow of urine
Causes--congenital causes of obstruction, Acquired causes of obstruction (including neurogenic, pregnancy) Even with complete obstruction, glomerular giltration persists and the filtrate subsequently diffuses back into the renal interstitium and is returned via lymphatics and veins. Unusually high pressure transmitted back through collecting ducts, can compress renal vasculature, one effect includes VENOUS STASIS, only later does glomerular filtration start to diminish. Irreversible damage occurs at about 3 weeks of complete obstruction, 3 months with incomplete obstruction. Massively Enlarged kidney Renal parenchyma compressed and atrophied (if this is a chronic proccess) Paradoxically, incomplete bilateral obstruction causes polyuria rather than oliguria at first. Unilateral hydronephrosis may remain silent for a long time |
