Renal Flashcards by Denisse Tiangco

Elevation of blood urea nitrogen and creatinine levels with dec GFR

Azotemia

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Hypoperfusion of kidneys
Dec GFR
No parenchymal damage

Prerenal azotemia

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Obstruction of urine flow below kidney

Relief of obstruction followed by azotemia

Postrenal azotemia

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Azotemia with clinical symptoms and biochem abnormalities

Uremia

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Glomerular injury 
acute onset of visible hematuria
proteinuria
azotemia
edema 
hypertension

Nephritis

Poststreptococcal glomerulonephritis

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Heavy proteinuria >3.5g per day, hypoalbuminemia
severe edema
hyperlipidemia
lipiduria

Nephrotic syndrome

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Crucial to maintenance of glomerular barrier function as diffusion barrier

Podocyte

Also synthesize GBM components

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transmembrane glycoprotein of the slit diaphragms between adjacent foot processes

Nephrin

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Maintains selective permeability of filtration barrier along with nephrin

Podocin

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Systemic and immunologically mediated diseases affecting glomerules

(SLE, Alport, DM, HUS)

Secondary glomerular disease

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Two forms of antibody assoc injury in glomerulonephritis:

1 deposition of soluble circulating antigen-antibody complex in glomerulus
2 antibodies reacting in situ within glomerulus

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pathogens that incite GN

1 streptococcal
2 Hepatitis B
3 Plasmodium falciparum malaria
4 Spirochetal

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Antigen-antibody complex producing injury through activation of complement and recruitment of leukocyte

Glomerulonephritis by immune complex

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Electron microscopy of GN show immune complexes on (4)

Mesangium 
Subendothelial (bet endothelial and GBM)
Subepithelial (bet outer GBM and podocyte)

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Complexes in endothelium and subendothelium elicit

Inflammatory reaction from infiltration of leukocyte and proliferation of glomerular cell

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Antibodies directed at subepithelial region of glomerulus produce

Noninflammatory lesions similar to Heymann nephritis or membranous nephropathy

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Antibodies directed fixed antigen in GBM
LINEAR pattern of staining
Conformational change in alpha3 chain of type IV collagen in GBM

Anti-glomerular basement membrane Antibody-mediated crescentic Glomerulonephritis

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Complication/sequelae of Anti-GBM Antibody-mediated GN with antibodies also cross reacting with basement membrane of lung alveoli

Goodpasture syndrome

simultaneous lung and kidney lesions

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Immune injury on Glomerulus pathophy

Complement activation via classical pathway:
Chemotactic agents C5a for neutrophil and monocyte
Protease release from neutrophils causing GBM degradation
O2 radical generation causing damage
Arachidonic acid metab causing dec GFR

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Antibody mediated GN show this type of pattern desposition

Granular

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Immune complex antibodies cause injury by

1 complement activation

2 leukocyte recruitment with mediator release sometimes damaging podocyte

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Nephrotic syndrome clinical complex (4)

1 massive proteinuria >3.5g/day
2 hypoalbuminemia <3g/dL
3 Generalized edema
4 hyperlipidemia and lipiduria

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Hyperlipidemia in nephrotic syndrome is caused by

Inc release of lipoproteins in liver or

Loss of lipoprotein synthesis inhibitors

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Most common cause of primary glomerular disease nephrotic in children

Minimal-change disease 65%

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Most common cause of primary glomerular disease nephrotic in adults

Focal segmental glomerulosclerosis 35% Membranous nephropathy 30%

Primary nephrotic renal disease occurs

95% in children

In adults, primary nephrotic disease is caused by

Renal manifestation of systemic disease 40%

Glomeruli have normal appearance by light microscopy but show uniform diffuse effacement of podocyte foot processes on EM Common at ages 1-7

Minimal change disease

90% of children respond to a short course of corticosteroid therapy

MCD 2/3 will have recurrence of proteinuria

FSGS may be secondary attributed to (5)

``` HIV Heroin IgA nephropathy 2 event Maladaptation to nephron loss Mutation in cytoskeletal proteins and podocin for integrity of podocyte and variant in apolopoprotein L1 gene APOL1 on chromosome 22 ```

Injury to podocyte as initiating event First affects some of glomeruli of JM Lesions occuring in some tufts within a glomerulus and sparing of others Inc mesangial matrix, obliterated capillary lumina, deposition of hyaline masses and lipid droplets

Focal segmental glomerulosclerosis

Collapse of glomerular tuft and podocyte hyperplasia | Poor prognosis

Collapsing glomerulopathy

Hematuria Hypertension Non selective proteinuria Poor response to corticosteroid

Focal segmental glomerulosclerosis

Subepithelial IgG deposit along GBM Diffuse thickening of capillary wall Chronic immune complex GN by antibodies against glomerular Ag. Without inflammation

Membranous nephropathy

Antigen most commonly recognized by causative antibodies in MN

Phospholipase A2

Spike and dome pattern | with granular deposits

Membranous nephropathy

MN may be caused by inciting events such as (5)

``` Infection Hep B, syphilis, schistosomiasis, malaria Malignancy CA of Lung, colon melanoma SLE Inorganic salt gold and mercury exposure Drugs (Penicillamine, captopril, NSAID) ```

Full blown nephrotic syndrome without antecedent illness Non-selective proteinuria Not responsive to corticosteroid Protein in 60%

Membranous nephropathy

Caused by circulating immune complex or planted antigen with in situ complex Assoc with Hepa B and C antigen, SLE, AV shunt

MPGN Type I

Excess compliment activation against C3 convertase or nephritic factor that lead to uncontrolled activation of alternative complement

MPGN Type II | Dense deposit disease

MPGN Type II is associated with mutations in gene encoding complent regulatory factor protein

factor H

Hypocomplementemia is marked in MPGN Type II due to

excessive consumption of C3 and reduced synthesis by liver

Glomeruli with lobular appearance, proliferation of mesangial and endothelial cell and infiltrating leukocytes GBM thickening

MPGN

Tram track or double contour capillary wall | Splitting of GBM

MPGN

subendothelial electron dense immune deposit | C3 in irregular pattern

Type I MPGN

Irregular, ribbon-like lamina densa and subendothelial space from unknown composition C3 present in irregular chunky segmental linear foci Complement dysregulation

Dense deposit disease

Poor prognosis recurring in transplant patients

MPGN type II

Underlying mechanism of proteinuria from immune and nonimmune causes

Podocyte injury

Nephritic syndrome complex

1 hematuria 2 oliguria and azotemia 3 hypertension

Glomerular deposition of immune complexes resulting in proliferation and damage to glomerular cells and infiltration of leukocytes esp neutrophils

Acute Postinfectious Poststreptococcal Glomerulonephritis

Others pathogens in Postinfectious GN

``` Pneumococcal Staph Mumps Measles Varicella Hep B, C ```

Inciting agent in Acute Postinfectious GN

Group A Beta Hemolytic Strep

Immune complex disease by complement activation of classical pathway Hypocomplementemia Granular deposits of IgG and complement on GBM

Poststrep GN

Antigen implicated in PSGN

Streptococcal exotoxin B (Spe B) | Streptococcal GAPDH

Increased cellularity of glomerular tuft (diffuse) Infiltrating neutrophils and monocytes Subendothelial, intramem or subepithelial humps of immune complexes against GBM Granular deposits of IgG and complement cleared over 2 months

APSGN

``` Smoky brown gross hematuria Oliguria/Azotemia HTN Low complement Inc anti-streptolysin O ```

PSGN

Gross hematuria within 1-2d of URTI | Most common cause of recurrent microscopic or gross hematuria

IgA Nephropathy

Most common nephritic glomerular disease revealed by renal biopsy

Iga Nephropathy

Deposition of IgA in IgA nepropathy occurs in

mesangium

Systemic syndrome involving skin, GI, joints and kidneys with IgA deposition in mesangium

Henoch-Schonlein Purpura

Abnormality (inc) in IgA production and clearance | Antibodies against abnormally glycosylated IgA depositing in mesangium activating alternative complement pathway

IgA Nephropathy

Secondary IgA nephropathy occurs in

Celiac disease | Liver disease defective hepatobiliary clearance

Immunoflorescence shows mesangial deposition of IgA with C3 either focal, diffuse or over crescentic

IgA nephropathy

IgA Nephropathy dx

biopsy

Hereditary disorders caused by mutation in genes encoding GBM proteins Nerve deafness Lens dislocation, Posterior cataracts, Corneal dystrophy

Hereditary nephritis | Alport Syndrome

Foam cells with fat and mucopolysaccharide accumulation in interstitial cells Thin basement membrane of glomeruli Basketweave appearance of lamina densa

Hereditary nephritis | Alport syndrome

X linked heterogenous mutation of gene encoding a5 type IV collagen M>F, Renal failure Persistent hematuria

Hereditary nephritis | Alport syndrome

``` Immunologically mediated 12% anti-GBM antibody mediated crescentic GN with or without lung involvement 44% immune complex GN with crescent 44% pauciimmune Severe glomerulus ```

Rapidly Progressive Glomerulonephritis

Linear IgG | C3 on GBM sometimes on alveolar capillary producing hemoptysis and renal failure

Goodpasture Syndrome | Anti-GBM Antibody-Mediated Crescentic Glomerulonephritis

Tx for goodpasture

Plasmapharesis

Enlarged pale kidneys with petechial hemorrhage on cortex | Crescents of parietal cell and mac into Bowman’s space

Anti-GBM Antibody-Mediated Crescentic GN

Lumpy bumpy pattern of staining for IgG/complement but does not respond to plasmapheresis

Immune-Complex Mediated Crescentic GN

Segmental necrosis and GBM break with crescent formation | Granular pattern of immune complex

Immune-Complex Mediated Crescentic Glomerulonephritis

Lack of anti-GBM antibodies or immune deposition + ANCA in serum Sometimes part of microscopic polyangiitis, wegener granulomatosis

Pauci-immune Crescentic GN

Segmental necrosis and GBM break with crescent formation | No deposits

Pauciimmune Crescentic GN

Nephritic syndrome with rapid loss of renal fxn

RPGN

severe glomerular injury with necrosis and GBM breaks and proliferation of crescent

RPGN

Principal causative organism in acute pyelonephritis

``` Enteric gram neg E coli - mc Proteus Klebsiella Enterobacter Pseudomonas ```

Most important and common route of bacterial infection in kidney

Ascending LUTI also hematogenous at times

Important cause of ascending infection allowing bacteria to ascend to pelvis

vesicoureteral reflux 20-40% in young children bec of congenital defect

Open duct at tip of papilla where urine can be propelled up

Intrarenal reflux

Discrete yellow raised abscess grossly apparent on renal surface Liquefactive necrosis with abscess within parenchyma Non affectation of glomeruli but of the rest

Acute Pyelonephritis

Necrosis of papilla from DM, obstruction and analgesia ischemic and suppurative of tips of renal pyramid Gray white necrosis of 2/3 of pyramids Coagulative necrosis

Papillary necrosis

Uneven scarring Scarring involving pelvis of calyxes Calyceal deformity

chronic pyelonephritis

Thyroidization with neutrophils Chronic inflammation Arteriolosclerosis Glomerulosclerosis

Chronic Pyelonephritis

Edema infiltration by mac and lymhpocytes

Drug induced nephritis Methicillin, thiazide, rifampin - interstitial non-necrotizing granuloma with giant cell NSAIDs- podocyte foot process effacement

``` Fever Eosinophilia Rash Renal abnormality 15 days after drug intake ```

Drug induced Interstitial nephritis

ATI by AKI

oliguria (<400mL/day)

Proteinaceous cast in distal tubule and duct along with hemoglobin in ischemic ATI

Tam-horsfall protein

Thickening and sclerosis of arterial wall and renal changes assoc with benign hypertension

Arterionephrosclerosis | Hyaline arteriosclerosis

Arterionephrosclerosis implicate mutations in

apolipoprotein L1 gene as in FSGS

Mutation in apolipoprotein L1 confers protection against

tyrpanosomal disease

Symmetric atrophy Diffuse fine granularity like grain leather Hyaline arteriosclerosis Fibroelastic hyperplasia of media

Arterionephrosclerosis

BP >200/120

Malignant hypertension

Kidney vessel injury Inc permeability to proteins, endothelial injury and platelet with fibrinoid necrosis of arterioles and small arteries PDGF and intimal hyperplasia lead to hyperplastic arteriolosclerosis Angiotensin II -> vasoconstriction Inc Aldosterone

Pinpoint petechial hemorrhage on cortical surface Flea-bitten appearance Fibrinoid necrosis of small vessel Onion skin appearance (Hyperplastic arteriolosclerosis)

Malignant hypertension

Malignant hypertension deaths 90% caused by

Uremia

Widespread thrombosis in microcirculation | Microangiopathic hemolytic anemia, thrombocytopenia, renal failure

Thrombotic microangiopathies

Cause of thromoangiopathy

``` Child HUS Adult HUS TTP Drugs Malignant hypertension scleroderma ```

Thrombotic microangiopathy pathogenesis

Endothelial activation (HUS) Platelet activation and aggregation (TTP) Small vessel thrombosis

75-% of cases following intestinal infection of Shiga toxin producing E coli or Shigella dysenteriae Type I targetting glomerular endothelial cell Damage leads to thrombosis

Thrombotic microangiopathy

Acquired defect in proteolytic cleavage of von Willebrand factor due to autoantibody or inherited defect

TTP

Autoantibodies are directed against this disintegrin and metalloprotease with thrombospondin like motifs in TTP

ADAMST 13 autoantibody binding leads to loss of function and inc large vWF multimers aggregation and thrombosis

25% of children with HUS will develop this consequence secondary to scarring after 25 years

Renal insufficiency CNS involvement TTP>HUS Kidney HUS>TTP

Progressive chronic renal damage assoc with HTN | Hyaline arteriosclerosis and narrowing of lumina with cortical atrophy

Arterionephrosclerosis

Severe elevation of BP Fibrinoid necrosis and hyperplasia of smooth muscle arterioles and artery Petechial hemorrhage on cortical surface

Malignant hypertension

Fibrin thrombi in glomeruli and small vessel -> AKI

Thrombotic microangiopathy

Childhood HUS is caused by endothelial injury from

E coli toxin

TTP is caused by

defect in vWF ADAMST 13 leading to thrombosis

``` Symmetrically contracted kidney Diffusely granular scarring of glomeruli Obliteration of glomeruli Marked interstitial fibrosis Unable to ascertain origin of injury ```

End stage kidney disease

Pathophysiology of hereditary cystic disease

defect in ciliacentrosome complex of tubular epithelial cell

1-5cm transluscent gray glistening smooth membrane filled with clear fluid single layer of cuboidal cell confined to cortex Smooth contours on xray, avascular

Simple cyst

Occur in kidneys of dialysis pxs Both in cortex and medulla Hematuria

Dialysis acquired cyst

Defective gene in 85-90% of families in AD PKD

PKD1 on ch 16

PKD1 encodes

complex cell membrane assoc proten Polycystin-1

Renal cystic disease is a type of

Ciliopathy bec polycystin is closely linked to primary cilium of tubular cells

hairlike organelles projecting into lumina from apical surface serving as mechanosensor of fluid flow

Cilia Polycystin mutation dysregulates mechanosensing downregulates cell polarity, proliferation and cell to cell adhesion

Mutations in 10-20% of cases caused by this gene Residing on chromosome Encoding protein

PKD2 4 Polycystin2

Ca permeable membrane channel expressed in cilia | Similar phenotype but slower rate of progression

Polycystin2

Large kidneys palpable with mass of cysts arising from nephrons on all levels Some may develop asymptomatic liver cyst 1/3 Produces symptoms only on 4th decade of life Intermittent gross hematuria

PCK 75% HTN 10-30% Saccular aneurysm of Circle of Willis and SAH

Autosomal recessive childhood PKD is from a mutation in

PKHD1 gene encoding receptor protein fibrocystin at ch6

Numerous small cyst in cortex and medulla Spongy kidney Bilateral Multiple cysts in liver and bile duct prolif

AR Childhood PKD

Most common form of nephronopthisis

Juvenile Others: infantile, adolescent, medullary cystic

Autosomal recessive form of nephronopthisis affects gene

NHP1-9 Encode components of cilia

``` Small contracted kidneys Small cysts at corticomedullary junction Chronic tubulointerstitial nephritis Polyuria polydypsia Unexplained chronic renal failure (diff to dx) ```

Nephronopthisis

AD inheritance by mutation in genes encoding polycystin1 and 2 10% of renal chronic failure Very large kidneys with cyst

Adult Polycystic Kidney Disease

Mutations in gene encoding fibrocystin Assoc with liver abnormality Numerous small cyst

Autosomal recessive PKD

Cause of chronic kidney disease in children AR Mutations encoding epithelial cell protein nephrocysti Contracted kidney with multiple SMALL cyst

Nephronopthisis

3 major stones

80% calcium oxalate or calcium phosphate 10% magnesium ammonium phosphate 6-9% uric acid or cysteine

Factors contributing to stone formation (4)

Concentration of solute Changes in pH Bacterial infection Inc urinary concentration of constituents exceeding solubility in urine (most important) supersaturation

50% of patients with calcium stone have

hypercalciuria but not hypercalcemia

50% of said patients with ca stone absorb ca in gut and excrete promptly in urine

absorptive hypercalciuria

primary renal defect of calcium reabsorption

renal hypercalciuria

Occurs in persistently alkaline urine from UTI | Proteus vulgaris, staph

Magnesium ammonium phosphate

Tendency to excrete persistently acidic urine less than 5.5 | Leukemia Gout

Uric acid stone

Genetically determined defect in renal transport protein of AA Acidic urine

Cysteine stone

80% unilateral, stones form in

Pelves and calyx | bladder

Branching structure creating cast on pelvis made up of magnesium phosphate

Staghorn calculi

Atresia of ureter, valve formation, aberrant renal artery compression, renal ptosis, kinking of ureter

Congenital hydronephrosis

Calculi, sloughed necrotic papillae

Acquired hydronephrosis foreign

BPH, Prostate carcinoma, papilloma and carcinoma tumor, malignant disease

Proliferative lesion

Prostatitis, uretritis, urethritis, retroperitoneal fibrosis

Inflammation

SC damage with paralysis of bladder

Neurogenic

Mild and reversible

Hydronephrosis from pregnancy

Blockage below level of ureters

Bilateral hydronephrosis

Dilation of pelvic calyx bec of continued filtration | Initial functional disturbance largely tubular manifested by impaired concentrating ability

Hydronephrosis Serious damage occurs after 3 weeks of complete obstruction 3 months in incomplete

Tumors of urinary tract are

twice as common as RCC

benign tumor from intercalated cells | central stellate scar, plethora of mitochondria

Oncocytoma

80-85% of primary malignant kidney tumors 2-3% of all cancers in adult 6-7th decade M>F

Renal Cell Carcinoma

RCC risk factors

Smoker HTN Cadmium exposure 30x in px with dialysis acquired cyst

65% most common Assoc with homozygous loss of VHL TSP Invades renal vein

Clear cell carcinoma

CCC of Kidney strongly assoc to

von Hippel Lindau

AD Predisposition to hemangioblastoma of cerebellum and retina Bilateral renal cyst

vHL

Palpable abdominal mass Painless hematuria Dull flank pain

Renal cell carcinoma

Assoc with increased expression and mutations of MET oncogene Bilateral, multiple

Papillary renal cell

Less common, not as clear as other renal cell carcinoma

Chromophobe renal cell carcinoma

3rd most common organ CA in children

Wilms tumor

Cells and tissue components of the tumor in Wilms are derived from

mesoderm epithelial serosa blastema

Renal Flashcards

(158 cards)