Glomerulonephritis Flashcards
definition
any immune mediated disease of the kidneys which affects the glomerulus (which causes secondary tubule-interstitial disease)
Damage to the endothelial or mesangial cells causes a what type of lesion?
proliferative lesion and causes red blood cells in the urine
damage to the podocytes causes a what type of lesion?
non-proliferative lesion with protein in the urine
why does damage to the podocytes cause a non-proliferative lesion
because damage to the podocytes causes atrophy
damage to the endothelial cells causes a
vasculitis
damage to the mesangial cells causes
the attraction of inflammatory cells
key investigations for any person presenting with suspected glomerulonephritis
- urinalysis= shows proteinuria or red blood cells
- urine microscopy= may show dysmorphic red block cells, lipiduria, red blood cells or glomerular casts
- 24 hour urine protein must be carried out as this is required to diagnose nephrotic syndrome
- FBCS= platelets and creatinine
- renal biopsy is the conclusive investigation
haematuria is either
asymptomatic microscopic haematuria or painless macroscopic haematuria
proteinuria quantification
- microalbuminuria (30-300mg albumin/day)
- asymptomatic protineuria (less than 1g/day)
- heavy proteinuria (1-3g per day)
- nephrotic range of proteinuria (more than 3g per day)
nephrotic syndrome
- proteinuria greater than 3g per day
- hypoalbunaemia (less than 30)
- hypercholesterolaemia
- oedema
nephrotic syndrome is indicative of a process affecting what type of cell
Podocytes
in nephrotic syndrome the loss of protein in the urine causes
hypoalbunaemia which causes a fall in the capillary oncotic pressure which causes fluid to shift from the vasculature into the tissues (albumin is the major protein which keeps fluid in the vasculature)
because of the hypoalabunaemia the liver
starts increasing its production of albumin but also increases its production of cholesterol which is not required causing hypercholesterolaemia
the proteins lost in neprhtoci syndrome also includes the loss of
antibodies (which are essentially proteins) so person is at increased risk of infection
reduced volume within the vasculature means
there is reduced venous return to the heart which causes reduced cardiac output which causes renal hypo perfusion which increased the risk of an AKI and causes the juxtaglomerular cells to produce renin which activates the RAAS system
what else is lost in nephrotic syndrome
anti-thrombin 3 which increases the risk of renal vein thrombi and pulmonary emboli
signs and symptoms of nephrotic syndrome
- xathelasma and xanthomata caused by hypercholesterolaemia
- leukonychia, peri-orbital oedema and peripheral oedema caused by hypoalbuminaemia
in nephrotic syndrome urine is described as
frothy in appearance
nephritic syndorme is indicative of
a proliferative process affecting endothelial cells
pathophysiology of nephritic syndrome
immune complexes get lodged in the glomerulus and elicit an inflammatory response with the recruitment of white cell causing damage allowing red blood cell to pass through into the filtrate
components of nephritic syndrome
- haematuria
- oliguria because the glomerulus is being damaged there is a reduction in glomerular filtration rate
- hypertension
- proteinuria can also occur but not to the same extent as in nephrotic syndrome
- active urinary sedimant= red blood cells, white blood cells and granular casts
classification of glomerulonephritis
classified according to its aetiology and histology
aetiology of glomerulonephritis
can be primary (idiopathic) which actually accounts for the majority of cases or secondary (caused by infection, drugs, malignancy or an underlying systemic disease)
histology of GN
- renal biopsy is examined under light microscopy, electron microscopy and immunofluorescence
histological classifications
- proliferative or non-proliferative (presence or absence of proliferation of mesangial cells)
- focal or diffuse (focal involves less than 50% of the glomeruli, diffuse involves more than 50% of the glomeruli)
- global or segmental (global involves the whole glomerulus, segmental only involves part of the glomerulus)
- Cresentic (presence of crescents: epithelial extra-capillary proliferation)
minimal change disease causes a
nephrotic syndrome
minimal change disease if the most common cause of what
nephrotic syndorme in children
pathophysiology of minimal change disease
podocytes have for processes which have a negatively charged coat which repels negatively charged molecules such as albumin, in minimal change disease T cells release cytokines which specifically damages the foot processes of the podocytes causing them to flatten out in a process called effacement , the change allows albumin to pass into bowmans capsule but does not allow other larger proteins through so there is a selective proteinuria
foot process effacement in minimal change disease
cannot be seen on light microscopy hence the name minimal change disease however, on electron microscopy foot process effacement can be seen
on immunofluorescence for minimal change disease
it is negative because the damage is caused by cytokines not immune complex deposition
minimal change disease will not cause
progressive renal failure
do you carry out renal biopsies for minimal change disease
only if it is unresponsive to steroids
treatment of minimal change disease
- 1st line= very response to oral steroid
- 2nd line= cyclophosphamide
focal segmental glomerulosclerosis causes a
Nephrotic syndrome
focal segmental glomerulosclerosis is the most common cause of what
nephrotic syndorme in adults
FSGS by breaking the work down
- focal means less than 50% of the glomeruli are affected
- segmental means only part of the glomeruli are affected
- glomerulosclerosis means scarring of the glomerulus occurs
FSGS can be
primary or secondary
primary FSGS means
idiopathic, podocytes are damaged and allow proteins and lipids into the filtrate, over time proteins and lipids get trapped in the glomerulus causing hyalinosis (tissue has a glassy appearance on histology) which eventually causes glomerulosclerosis
secondary FSGS
- HIV (HIV associated nephropathy)
- Heroin (heroin associated nephropathy)
- Sickle cell disease
Histology of focal segmental glomerulosclerosis
segmental sclerosis and hyalinosis
electron microscopy of FSGS
foot process effacement
on immunofluoresces of FSGS
there may be non-specific focal despots of IgM and comleemtn proteins (but this is not always present)
treatment of focal segemtla glomerulosclerosis
60% achieve remission with prolonged steroids but 50% progress to end stage renal failure within 10 years
membranous nephropahty cuases a
nephrotic syndrome
membranous nephrotpathy is caused by
damage and inflammation to the glomerular basement membrane which causes the basement membrane to become more permeable allowing proteins to enter the filtrate
membranous nephropathy is the
second most common cause of nephrotic syndrome in adults
the damage in membranous nephropathy is caused by
immune complexes either autoantibodies directly targeting the glomerular basement membrane or immune complexes formed outside the kidney and deposit in the glomerular basement membrane
immune complexes in membranous glomerulonephritis are called
sub-epithelial deposits because they are between the podocytes and the glomeruarl basement membrane
sub-epithelial deposits activate the
complment system which produces membrane attack complex which damages the podocytes and mesangial cells
mesnagial cells are the cells
that remove debris
the immune reaction occurring in membranous nephropathy also
recruits inflammatory cells which release proteases and oxidants causing damage to the GBM, over time as a reaction to the immune deposits GBM matrix gets laid down between the immune complexes which makes the GBM appear thicker on histology
in membranous nephropathy/ glomerulonephritis on electron microscopy
there is a characteristic spike and dome pattern
on immunoflourecence for membranous nephropathy there are
deposits of immune complex
membranous nephropahty is usually
primary (idiopathic) there other cases are secondary and are caused by autoantibodies generated in response to infection (hep B), malignancy (lymphoma, carcinomas), auto-immune disease (SLE), drugs (penicillaemine, gold)
why is it important to known whether membranous nephrotpathy is primary or secondary
because if someone has secondary nephropathy and you treat them as you would in primary it could kill them i.e. someone with hep B
treatment of primary membranous nephropathy
Steroids/alkyalting agents/ B cell monoclonal antibodies
treatment of secondary membanous nephropathy
treat the underlying cause
30% of people with membranous glomerulonephritis
progress to end stage renal failure within 10 years
IgA nephropathy is the
commonest type of glomerulonephritis in the world
IgA nephropathy occurs when an
abnormal IgA froms and deposits in the kidneys causing damage
in IgA nephropahty the
abnormal glycosylation of the hinge region of the IgA1 causing them to be galactose deficienct so they are not recognised by the body and accumulate, they are also considered to be non-self so the body generates IgG antibodies in reponse which bind to abnormal IgA-1 forming an immune complex and deposit at sites throughout the body
the abnormal immune complexes specifically deposit in
the mesangium which activates the alternative complement pathway leading to the release of pro-inflammatory cytokines and the migration of macrophages causing glomerular injury allowing red blood cells to enter the filtrate causing a nephritic syndrome
IgA nephropathy causes a
nephritic syndrome
IgA nephropathy classically present in
childhood as a microscopic or macroscopic haematuria and usually develops during an infection involving the mucosal lining (infection of the GI or respiratory tract)
During each infections in IgA nephropathy
there is increased production of IgA-1 so there is increased immune complex deposition therefore, over many decades it can progress to end stage renal failure
in IgA nephropathy there is what seen on light microscopy
meangial cell proliferation
in IgA nephropathy there is what seen on electron microscopy
IgA immune complex deposition in the measngium (and on immunofluorescence)
IgA nephroapthy is associated with
hence schoenlen purpura but HSP affects other parts of the body
treatment of IgA nephropathy
- once the kdiensy have been scarred this cannot be reversed however progression can be slowed by blood pressure control (reducing salt intake and ACE inhibitors)
post-streptococcal glomerulonephritis
glomeruli become inflamed after a streptococcal infection (commonly group A strep)
infection by group A strep initiates a
type 3 hypersensitivity reaction where immune complexes are formed (often IgG or IgM antibodies) which deposit in the glomerular basement membrane at the sub-epithelium, this causes an inflammatory reaction causing activation and deposition of C3 complement and release of inflammatory cytokines and proteases which damage the glomerulus and allows protein and red blood cells into the urien
post- streptococcal glomerullonephritis causes a
nephritic syndrome
post-streptococcal glomerulonephritis usually affects
children
- either 1-2 weeks after a throat infection
- 6 weeks after a skin infection such as impetigo
on light microscopy for post-streptococcal glomerulonephritis
the glomerulus looks enlarged
on electron microscopy for post-streptococcal glomerulonephritis there is
sub-epithelial depostiion
on immunofluorescence for post-streptococcal GN
there is a starry sky granular appearance of the GBM and mesangium
blood test in post-strep GN show
- antibodies against group A strep
- decreased complement levels
treatment for post-streptococcal glomerulonephritis
usually is spontaneously resolving but in some children can develop acute renal failure and one quarter of adults with post-streptococall GN develop rapidly progressive GN
rapidly progressive glomerulonephritis is also called
crescentic glomerulonephritis
rapidly progressive glomerulonephritis causes a type of
nephritic syndrome
inflammation of the glomerulus causes
proliferation of the cells in bowmans space forming a crescent shape which leads to renal failure within days/ weeks
rapidly progressive glomerulonephritis can be
idiopathic or if there is a known cause it is categorised
type 1 rapidly progressive GN
anti-glomerular basement membrane antibodies as seen in good pastures syndrome
type 2 rapidly progressive GN
immune complex mediated as seen in post-streptococcal GN, SLE, IGA NEPHROPAHY AND HENOCH SCHOENLEN PURPURA
Type 3 rapidly progressive GN
paucci immune (no anti-GBM and no immune complexes) ANCA is seen (anti- neutrophil cytoplasmic antibodies) which are antibodies against the bodies own neutrophils
type 3 is further divided into
c-ANCA and p-ANCA
c-ANCA is seen in
GPA
p-ANCA is seen in
microscopic polyangittis and eosinohilis grnaulomatosis with polyangiiits
typically in rapidly progressive GN because of
cell mediated immunity and macrophages involvement the GBM breaks allowing red blood cells, inflammatory mediators, proteins and fibrin to enter the bowmans space, this allows monocytes and macrophages to enter bowmans spaces as well as parental epithelial cells which proliferate forming a thick characteristic crescent shape, over time crescent ca undergo sclerosis and be replaced with connect tissue
on light microscopy rapidly progressive GN shows
a crescent shape
the types of secondary rapidly progressive GN can be differentiated using
immunofluorescence
type 1= linear pattern
type 2= granular pattern
type 3= negative as it is pouch immune
treatment of rapidly progressive GN shouldd be
prompt with potent immunosuppression with supportive dialysis if required
immunosuppression used
steroids or cytotoxic (cyclophosphamide/ mycopentolate/ azathioprine), plasmapheresis is usually sued in combination
