Week 10 Pathology of the urinary system Flashcards
What are the 4 main sites within the cortex that pathologies present in?
glomerular
Tubular- often PCT
Interstitial
Vascular - vessels
what layers make up the filtration barrier of the glomerulus?
fenestrated endothelial cells
glomerular basement membrane- has a -ve charge repelling proteins, lattice in structure creating a physical barrier
podocytes- projecting
If one part of the nephron is altered will it affect the rest and why?
yes for example if the glomerulus is damaged or blocked will affect the rest of the nephron as the blood supply will be affected
What two basic things can happen to the filter causing pathology?
filter can block- renal failure = decreased GFR
filter can leak- proteinuria- mainly albumin, haematuria, one, other or both
what is primary and secondary kidney injury?
primary- pathology directly affecting the kidneys
secondary- pathology affecting the whole body with secondary affect on the kidneys- eg DM
In what age group do medulla pathologies usually occur?
in children- kidneys not formed properly
genetic
what is the main difference between nephrotic and nephritic syndromes?
nephrotic leaking protein
nephritic leaking blood
what are some primary and secondary causes of nephrotic syndrome?
Primary:
- minimal change glomerulonephritis
- focal segmental glomerulosclerosis (FSGS)
- membranous glomerulonephritis
Secondary:
- DM
- amyloidosis
describe minimal change glomerulonephritis- who affected, characterised by, microscopic changes seen- EM, pathogenesis, treatment, progression to renal failure?
occurs mainly in childhood/adolescence - incidence reduced with increasing age
- heavy proteinuria or nephrotic syndrome
- nothing seen on normal microscope, EM shows no/injured podocytes- lost filtering mechanism
- damage due to unknown circulating factor- no immune complex deposition
- responds to high dose of steroids- may reoccur when stop
- usually no progression to renal failure
describe FSGS- who affected, charecterised by, microscopic changes seen- EM, causes, treatment, progression to renal failure?
- nephrotic syndrome seen in adults- cross over period with minimal change
- glomerulosclerosis- scaring on glomerulus- looks abnormal microscopically
- circulating factors damage podocytes
- less responsive to steroids
- can progress to renal failure- scaring leads to failure- ned for transplantation/dialysis if steroids dont work
describe membranous glomerulonephritis- who affected, characterised by, causes, microscopic changes seen- EM
- commonest cause of nephrotic disease in adults
- rule of thirds- 1/3 get better, 1/3 have some renal failure but dont deteriorate, 1/3 deteriorate- need transplant/dialysis
- immune complexes deposited - probably autoimmune
- complex= antigen bound to IgG antibody- form lumps- get stuck in kidney- podocyte damage- proteinuria
- may be secondary eg lymphoma- immune crossover
- membrane looks abnormal- thicker- roughened around outside
describe the pathogenesis of subepithelial immune deposits- how do they get there and what do they do?
deposits under podocytes damage them in subendothelium
- cannot wet through basement membrane so must be a molecule on the podocyte that immune system responds to and attacks
how can DM lead to nephrotic syndrome?
- progressive, condition can affect the glomerulus- renal failure
- DM affects microvascular- eg eyes, kidneys have extensive blood supply so also affected
- results in big nodules of scaring in glomerulus which disrupts barrier allowing proteins to leak out
describe nephrotic syndrome- what it is, site and some consequences
kidney leaking lots of protein- more than 3.5G in 24hrs
- SITE- damaged podocytes- filter mechanism- cant stop protein leaking out
- leads to a drop in oncotic pressure- fluid moves out into interstitium causing oedema
- also causes hypercholesterolaemia- apoproteins lost in urine so nothing to bind and remove cholesterol from the blood
describe nephritic syndrome
more acute- usually present sick and need rapid care- blood in urine
- SITE- endothelium damage- blockage
blocking syndrome- hypertension and AKI
what are the main causes of haematuria/ nephritic syndrome?
haematuria:
- IgA nephropathy- most common cause - Ig A deposited in nephron
- thin glomerular basement membrane disease/ hereditary nephropathy (alport)
nephritic syndrome:
- goodpasture syndrome (anti- GBM disease)- direct antibody to basement membrane- have to filter it out- most = renal failure
- vasculitis- inflammation of blood vessels- rapidly= renal failure if not treated
describe IgA nephropathy- who affected, presentation, characteristics, treatment, progression to renal failure?
commonest glomerulonephritis- affects any age
- present with visible/invisible haematuria
- relationship with mucosal infections- IgA what defends mucous membranes
- +/- proteinuria
- no effective treatment
- signif proportion progress to renal failure
what is mesangial damage- what occurs, how, immune complexes deposited?
mesangial is the structure which support the capillaries
when damaged- glomerulus responds by proliferating- too many mesangial cells and matrix
- mesangium is not protected basement membrane so normal circulating IgA stops here forming complexes as can get to it- IgA nephropathy
describe the hereditary nephropathies (haematuria)- thin GBM nephropathy and alport
thin GBM nephropathy- also called benign familial nehropathy
- isolated haematuria- doesnt go into renal failure
- thin GBM, benign course- often detected by accident when having a scan as no symptoms
Alport- X linked
- abnormal collagen IV in basement membrane- abnormal GBM
- progresses to renal failure
describe goodpasture syndrome (anti- GBM) (nephritic syndrome)- onset, associations, microscopic appearance-EM, cause, treatment
- uncommon but severe- rapidly progressive GN
- acute onset of severe nephritic syndrome- AKI overnight, hypertension
- associated with pulmonary haemorrhage in SMOKERS- type 4 collagen in alveoli membrane also
- autoantibody (IgG) to collagen IV in basement membrane- collagen must be specialised in kidneys why doesnt affect all membranes
- whole glomerulus attacked and damaged- lots of inflammatory cells seen= scaring if dont treat
- treatable by immunosuppression (turn of immune system) and plasmaphoresis (filter plasma) if caught early
describe vasculitis (nephritic syndrome)- what is it, immune complexes?, associations, presentation, microscopic appearance-EM, treatment
group of systemic disorders
- no immune complexes/ antibody deposition
- associated with Anti- neutrophil cytoplasmic antibody (ANCA)- antibody that attacks neutrophils- breaks down endothelium
- nephritic appearance
- crescent shaped mass of inflammatory cells seen, segmental necrosis- if affects lots= renal failure
- treatable if caught early, urgent biopsy needed
