Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/58

Click to flip

58 Cards in this Set

  • Front
  • Back

Responses to glomerular injury

Hypercellularity


Basement membrane thickening


Hyalinisation


Sclerosis

Responses to glomerular injury


Hyperceullarity

Proliferation - mesangial, endothelial


Leukocyte infiltration


Crescents - severe - epithelial cells (mostly parietal and leukocytes)


Acute, inflammatory diseases

Responses to glomerular injury


Basement membrane thickening

Appears as thickening of capillary walls


Deposition of amorphous electron-dense material on the endothelial or epithelial side of the basement membrane or within the GBM itself


Chronic

Responses to glomerular injury


Hyalinisation

Accumulation of homogenous pink material (plasma proteins)


Fills capillary lumens


Consequence of endothelial or capillary wall injury - end results of various forms of glomerular damage


Chronic

Responses to glomerular injury


Sclerosis

Extracellular collagenous matrix - mesangial, capillary loops -> obliteration of capillary lumens -> fibrous adhesions between the sclerotic portions of the glomeruli and nearby parietal epithelium


Chronic

Patterns of glomerular disease

Focal - <50% of glomeruli affected


Diffuse - ≥50% of glomeruli affected




Segmental - Involving only part of the glomerular tuft


Global - involving all of the glomerular tuft

Characteristics of Nephrotic syndrome

Massive proteinuria >3.5 g/day


Hypoalbuminaemia <3g/dL


Generalised oedema


Hyperlipidaemia and lipiduria




Hypercoagulatbility


Hypogammaglobulinaemia


Hypocalcaemia

Mechanism of Nephrotic syndrome

Structural and/or charge change in glomerulus capillary wall


--> increased permeability


--> heavy proteinuria


--> loss of albumin, immunoglobulins, loss of antithrombin 3




Loss of albumin --> hypoalbuminaemia --> oedema





Glomerular disease with nephrotic syndrome

Minimal change disease


Focal Segmental Glomerulosclerosis


Membranous glomerulonephropathy


Membranoproliferative glomerulonephritis


Diabetic glomerulosclerosis

Minimal change disease


Presentation and pathology

Nephrotic with selective loss of albumin and not immunoglobulins


Most common cause of nephrotic syndrome in children


Usually idiopathic


Often associated with atopic conditions, respiratory infection, vaccines, Hodgkin lymphoma and NSAID use




Cytokines cause podocyte injury --> effacement of foot processes

Minimal change disease


LM, IF, EM

LM - normal, may see lipid in PCT




IF - Negative




EM - foot process effacement, no deposits

Minimal change disease


Management and prognosis

Excellent response to steroids


Exclude precipitative factors


Manage symptoms




Remission in majority

Focal segmental glomerulosclerosis


Presentation and pathology

More common in adults than in children


Nephrotic syndrome




10-15% primary, 85-95% secondary


May be associated with HIV, heroin use, sickle cell disease, and/or obesity


Secondary to glomerulonephritis


End-point for many diseases due to loss of nephrons and hyperfiltration injury




Endothelial cell damage --> entrapment of plasma proteins --> sclerosis and hyalinisation

Focal segmental glomerulosclerosis


LM, IF, EM

LM -


Focal and segmental sclerosis and hyalinisation


Increased mesangial matrix


Obliteration of capillary lumina


Lipid droplets


Collapsing glomerulopathy




IM


Focal, IgM and C3




EM


Foot process effacement

Focal segmental glomerulosclerosis


Management and prognosis

Primary - poor response to steroids


Treat proteinuria


Treat underlying disease if secondary




50% renal failure in 10 years


20% renal failure in 2 years


High recurrence rate in transplants

Membranous glomerulopathy


Presentation and pathology

Nephrotic


Most common cause of nephrotic syndrome in adults




75% primary - antibodies against PLA2R on podocytes


25% secondary - SLE, Drugs (e.g. NSAIDs), underlying malignancy, chronic infections other autoimmune diseases (e.g. diabetes, thyroiditis)




Chronic immune complex-mediated capillary wall injury --> thickening of basement membrane --> thickening of GBM

Membranous glomerulopathy


LM, IF, EM

LM


Diffuse thickening of GBM


Open capillary lumen


Siver stain reveals spikes on GBM




IF


Granular IgG and C3




EM


Subepithelial deposits


Spikes of BM material - spike and dome appearance


Foot process effacement

Membranous glomerulopathy


Management and prognosis

Treatment of underlying disease


ACEI or ARB


Immunosuppression




Natural history - 30% spontaneous remission, 30% persistent proteinuria, 30% progressive renal failure



Membranoproliferative glomerulonephritis


Presentation and pathology

Nephrotic and/or nephrotic syndrome


10% of cases of nephrotic syndrome in children




Type 1 (80%) - circulating immune complexes


associated with Hep B and Hep C




Type 2 (dense deposit disease) - excessive complement activation due to C3 nephritic factor (autoantibody)


More likely to be nephritic




Both lead to complement activation

Membranoproligerative glomerulonephritis


LM, IF, EM

LM


Large hypercellular glomeruli with lobular appearance


Tram-track appearance - GBM thickening and splitting


Proliferation of mesangial and endothelial cells




IF


Type 1: granular - IgG, C3/C1q


Type 2: discontinuous linear - C3




EM


Type 1: subendothelial deposits


Type 2: intramembranous deposits

Membranoproliferative glomerulonephritis


Management and prognosis

Poor response to steroids




Slowly progress, unremitting course


50% renal failure within 10 years


Can recur in transplants

Diabetic glomerulonephritis


Presentation and pathology

Nephrotic, microalbuminuria, azotaemia


ESRF




Non-enzymatic glycosylation of vascular basement membrane proteins -> hyaline arteriosclerosis


Haemodynamic changes -> increase GFR -> hyperfiltration -> glomerular hypertrophy

Diabetic glomerulonephritis


LM, IF, EM

LM


Global and diffuse


Capillary basement membrane thickening


Mesandial sclerosis and expansion - Kimmelstiel-wilson nodules


Nodular glomerulosclerosis


Accumulation of hyaline material




IF


Linear homogenous weak to moderate reactivity for IgG and albumin




EM


Diffuse thickened GBM, no deposits

Diabetic glomerulonephritis


Management and prognosis

ACEI - dilation of efferent arteriole




~30-40% of diabetes mellitus patients develop sever or end stage renal insufficiency

Characteristics of nephritic syndrome

Haematuria + red blood cell casts in urine


Azotaemia


Oliguria


Mild-moderate hypertension and periorbital oedema


Mild proteinuria

Mechanism of nephritic syndrome

Inflammation of glomeruli -> glomerular cell proliferation -> obstruction of capillary lumen




-> capillary rupture -> haematuria and proteinuria (mild)




-> decreased GFR -> acute renal failure and sodium and water retention

Post-Streptococcal Glomerulonephritis


Presentation and Pathology

Nephritic


Most common in children aged 6-10 years


Occurs 2-3 weeks after infection with Group A, beta-haemolytic streptococcal infection (skin or pharynx)




Trapped immune complexes - streptococcal Ag and specific Ag

Post-streptococcal glomerulonephritis


LM, IF, EM

LM


Enlarged hypercellular glomeruli = leukocytes, mesangium, endothelial proliferation


+/- crescent formation if severe




IF


"Lumpy bumpy"


Granular IgG and C3 in GBM and mesangium




EM


Subepithelial humpsPost

Post-streptococcal Glomerulonephritis


Management and prognosis

Supportive therapy




>95% of children recover completely, 1% progress to renal failure


60% of adults fully recover, some go on to develop RPGN

Alport syndrome

Inherited defect in type IV collagen; most commonly X-linked


Results in thinning and splitting of glomerular basement membrane


Isolated haematuria, sensory hearing loss, ocular disturbances

IgA Nephropathy (Berger disease)


Presentation and pathology

Children and young adults


Recurrent Haematuria and RBC casts


Usually follows an URTI, GIT infection or UTI


Most common glomerulonephritis worldwide


Primary or secondary - HSP, Liver disease, psoriasis, coeliac disease, IBD, HIV




Increased plasma IgA -> IgA deposition in mesangium -> mesangial widening and proliferation

IgA nephropathy


LM, IM, EM

LM


Mesangial expansion with some increase in cellularity, capillary loops still open




IF


Granular IgA +/- C3 in mesangium




EM


Mesangial and paramesangial deposits

IgA nephropathy


management and prognosis

Depends on clinical parameters and indication of severity/progression


Management of blood pressure and proteinuria




30-40% microscopic haematuria only


5-10% acute nephritic syndrome


15-40% slow progression to CRF over 20 years


Can recur in transplanted kidney


Increased risk of progression: onset in old age, heavy proteinuria, hypertension, extent of glomerulosclerosis

Type 1 Rapidly progressive glomerulonephritis


Presentation and pathology

Anti-GBM disease




Young adult males


Haemoptysis


Rapid and progressive loss of renal function - severe oliguria, nephritic syndrome




Good pasture syndrome


Circulating IgG against collagen in glomerular and alveolar basement membranes


Also associated with lung pathology

Type 1 Rapidly progressive glomerulonephritis


LM, IF, EM

LM


Focal and segmental


Crescents - fibrin and macrophages


Segmental necrotising lesions


Silver stain - discontinuous GBM




IF


IgG linear pattern




EM


GBM wrinkling and rupture

Type 1 Rapidly progressive glomerulonephritis


Management and prognosis

Steroids, cytotoxic drugs, plasmapheresis




20% die


60% end stage renal disease


20% recover




Can recur in transplants

Type 2 Rapidly Progressive Glomerulonephritis


Presentation and pathology

Immune Complex


Rapid and progressive loss of renal function - severe oliguria, nephritic syndrome




Idiopathic, and immune complex nephritides (eg.Post-infectious GN (most common), IgA nephropathy) or systemic immunologicdisease (e.g. SLE)



Type 2 Rapidly Progressive Glomerulonephritis


LM, IF, EM

LM


Focal and segmental


Crescents - fibrin and macrophages


Segmental necrotising lesions


Silver stain - discontinuous GBM




IF


IgA granular - HSP/IgA glomerulonephritis


IgG+C1q - SLE




EM


GBM wrinkling and rupture

Type 3 Rapidly Progressive Glomerulonephritis


Presentation and Pathology

Pauci Immune


Rapid and progressive loss of renal function - severe oliguria, nephritic syndrome




Neither immune complex or anti-GBM antibodies


Majority are ANCA positive


pANCA MPO - microscopic polyangitis


cANCE PR3 - Wegeners granulomatosis


Churg strauss - inflammation, eosinophils and asthma



Type 3 Rapidly Progressive Glomerulonephritis


LM, IF, EM

LM


Focal and segmental


Crescents - fibrin and macrophages


Segmental necrotising lesions


Silver stain - discontinuous GBM




IF


Negative




EM


GBM wrinkling and rupture

Type 3 Rapidly Progressive Glomerulonephritis


Management and prognosis

Steroids AND cytotoxic drugs




Remission rate better the significant immunosuppressants than with corticosteroid alone

Congenital Renal Abnormalities

10% of live births




Agenesis


Hypoplasia


Ectopic kidney


Horseshoe kidney


Obstruction of pelviureteric junction


Double ureters

Renal Agenesis

Bilateral


Not compatible with life


Potter sequence - lung hypoplasia, flat face and low set ears, developmental defects of extremeties.




Unilateral.


Compatible with life unless other congenital abnormalities are severe/


Leads to hypertrophy of existing kidney -> hyper filtration -> increased risk of renal failure later in life

Renal hypoplasia

Renal failure occurs in early childhood if bilateral.




If unilateral - difficult to differentiate from atrophy from other causes - No scars, reduced number of renal lobes and pyramids.

Ectopic kidney

Kidney in an abnormal location - usually lower in the abdomen.


May or may not be smaller in size.


Ureters can become kinked -> outflow obstruction --> hydronephrosis

Double ureters

Results from split in the ureteric bud.


Often associated with double renal pelvis.


If unilateral - no clinical significance

Adult Polycystic kidney disease


Inheritance, presentation and prognosis

Autosomal dominant inheritance (PKD1- 85%, PKD2-15%)




Asymptomatic until 20-30s


Insidious onset haematuria


Progressive kidney disease


Flank pain


UTI


Hypertension




40% die of coronary or hypertensive heart disease


25% die of infection


15% die from ruptured berry aneurysm/hypertensive cerebral haemorrhage

Adult Polycystic kidney disease


Gross morphology and extra-renal features

Bilaterally enlarged


Mass of cysts 3-4 cm


Cysts filled with clear serious fluid to turbid red brown fluid


No obvious intervening parenchyma


Cysts visible on outside of kidney




Polycystic liver disease


Berry aneurysms


Mitral valve prolapse


Cysts in spleen, pancreas, lung

Childhood Polycystic Kidney disease


Inheritance, presentation and prognosis

Autosomal recessive


PKHD1 - chromosome 6p - encodes an integral membrane protein




Serious manifestations usually present at birth


4 subcategories - perinatal, neonatal, infantile, juvenile




Variable prognosis

Childhood Polycystic Kidney disease


Gross morphology and extra-renal features

Bilaterally enlarged kidneys with smooth external appearance


Numerous cysts in cotex and medulla give sponge-like appearance




Liver cysts


Portal fibrosis -> congenital hepatic fibrosis -> signs and symptoms of portal hypertension

Multicystic renal dysplasia


Presentation and prognosis

If bilateral - renal failure


Unilateral - good prognosis, can be corrected with surgery

Multicystic renal dysplasia


Gross morphology and extra-renal features

Unilateral or bilateral enlarged kidney(s)


Irregular with cysts of variable size




Urinary tract abnormalities

Medullar sponge kidney


Presentation, gross morphology and prognosis

Haematuria, UTI, recurrent renal stones




Multiple systemic dilatations of collecting ducts in medulla




Excellent prognosis

Nephronothisis-medullary cystic disease complex


Inheritance and presentation

Can be sporadic, autosomal recessive or dominant


Sporadic - 20%


Familial juvenile - 40-50% - AR


Renal-retinal dysplasia - 15% - AR


Adult-onset medullar cystic disease - 15% - AD




Polyuria and polydipsia

Nephronothisis-medullar cystic disease complex


Gross morphology and extra-renal features

Small kidneys with contracted granular surface


Cysts in medulla - particularly at aorticomedullar junction




Depending on variant


Ocular motor abnormalities


Retinitis pigmentosa


Liver fibrosis

Acquired renal cystic disease

Sporadic




Haemorrhage, erythrocytosis, neoplasia




Simple or multiple cysts, usually in cortex




Occurs with dialysis

Haemolytic uraemic syndrome

Triggered by shiga-like toxin produced by bacteria - e.g. E. coli

Presents with influenza-like/diarrhoeal prodrome - sudden onset harmatemesis/malena, oliguria, haematuria, microangiopathic haemolytic uraemia, thrombocytopenia +/- neurological c...

Triggered by shiga-like toxin produced by bacteria - e.g. E. coli




Presents with influenza-like/diarrhoeal prodrome - sudden onset harmatemesis/malena, oliguria, haematuria, microangiopathic haemolytic uraemia, thrombocytopenia +/- neurological changes




Excessive platelet activation

Malignant nephrosclerosis

Malignant hypertension -> vascular injury -> increased endothelial permeability -> focal death of cells, platelet deposition -> fibrinoid necrosis and hyperplastic arteriolitis




Onion skinning




'Flea-bitten' kidney