Week 10 Pathology of the urinary system

Question 1

What are the 4 main sites within the cortex that pathologies present in?

Answer 1

glomerular
Tubular- often PCT
Interstitial
Vascular - vessels

Question 2

what layers make up the filtration barrier of the glomerulus?

Answer 2

fenestrated endothelial cells
glomerular basement membrane- has a -ve charge repelling proteins, lattice in structure creating a physical barrier
podocytes- projecting

Question 3

If one part of the nephron is altered will it affect the rest and why?

Answer 3

yes for example if the glomerulus is damaged or blocked will affect the rest of the nephron as the blood supply will be affected

Question 4

What two basic things can happen to the filter causing pathology?

Answer 4

filter can block- renal failure = decreased GFR

filter can leak- proteinuria- mainly albumin, haematuria, one, other or both

Question 5

what is primary and secondary kidney injury?

Answer 5

primary- pathology directly affecting the kidneys

secondary- pathology affecting the whole body with secondary affect on the kidneys- eg DM

Question 6

In what age group do medulla pathologies usually occur?

Answer 6

in children- kidneys not formed properly

genetic

Question 7

what is the main difference between nephrotic and nephritic syndromes?

Answer 7

nephrotic leaking protein

nephritic leaking blood

Question 8

what are some primary and secondary causes of nephrotic syndrome?

Answer 8

Primary:

• minimal change glomerulonephritis
• focal segmental glomerulosclerosis (FSGS)
• membranous glomerulonephritis

Secondary:

• DM
• amyloidosis

Question 9

describe minimal change glomerulonephritis- who affected, characterised by, microscopic changes seen- EM, pathogenesis, treatment, progression to renal failure?

Answer 9

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

Question 10

describe FSGS- who affected, charecterised by, microscopic changes seen- EM, causes, treatment, progression to renal failure?

Answer 10

• 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

Question 11

describe membranous glomerulonephritis- who affected, characterised by, causes, microscopic changes seen- EM

Answer 11

• 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

Question 12

describe the pathogenesis of subepithelial immune deposits- how do they get there and what do they do?

Answer 12

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

Question 13

how can DM lead to nephrotic syndrome?

Answer 13

• 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

Question 14

describe nephrotic syndrome- what it is, site and some consequences

Answer 14

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

Question 21

describe nephritic syndrome

Answer 21

more acute- usually present sick and need rapid care- blood in urine
- SITE- endothelium damage- blockage
blocking syndrome- hypertension and AKI

Question 22

what are the main causes of haematuria/ nephritic syndrome?

Answer 22

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

Question 23

describe IgA nephropathy- who affected, presentation, characteristics, treatment, progression to renal failure?

Answer 23

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

Question 24

what is mesangial damage- what occurs, how, immune complexes deposited?

Answer 24

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

Question 25

describe the hereditary nephropathies (haematuria)- thin GBM nephropathy and alport

Answer 25

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

Question 26

describe goodpasture syndrome (anti- GBM) (nephritic syndrome)- onset, associations, microscopic appearance-EM, cause, treatment

Answer 26

• 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

Question 27

describe vasculitis (nephritic syndrome)- what is it, immune complexes?, associations, presentation, microscopic appearance-EM, treatment

Answer 27

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