Glomerula Disease Flashcards
How does the glomerulus structure change in glomerulonephritis?
Narrowed capillary lumen
Subepithelial immune complexes
Increased mesangial cells
Fusion of foot processes
PMN leukocytes present
What is glomerlonephritis? What 4 structures can be damaged from it?
Inflammation of glomeruli
Group of diseases including: nephrotic syndrome and nephritic syndrome
4 structures: Capillary endothelium Glomerular basement membrane Mesangial cells Podocytes
Often involves the immune system
What are the 4 classifications of glomerulonephritis, give an example of each?
Clinical presentation - nephrotic/ nephritic
Histological appearance - minimal change disease; membranous nephropathy/ focal segmental glomerulosclerosis
Diagnosis- Anti-GBM disease, ANCA- associated vasculitis, lupus
Primary (attacks kidney) or secondary (systemic including kidney)
What different forms can glomerulonephritis clinically present as?
- Asymptomatic haematuria &/ or proteinuria - urine dipstick
- Chronic glomerulonephritis
- Acute glomerulonephritis (has to be nephritic syndrome)
- Rapidly progressive glomerulonephritis (often too quick for nephritic syndrome)
- Nephrotic syndrome
Describe nephritic and nephrotic syndrome
Nephritic syndrome - inflammation disrupting glomerular basement membrane -> haematuria
Nephrotic syndrome - podocyte damage leading to glomerular charge-barrier disruption -> proteinuria
What’s the triad for nephrotic syndrome and what are some other features of it?
Triad:
- proteinuria >350mg/ mmol
- hypoalbuminaemia
- oedema
Usually accompanied by high cholesterol
Other features:
BP often normal
Creating may normal
Proteinuria >350mg/mmol alone = nephrotic range proteinuria
Causes of nephrotic syndrome
Primary renal disease:
Minimal change disease (Unknown’ cause), membranous nephropathy (immune complexes in glomeruli), focal segmental glomerulosclerosis (scarring of glomeruli)
Secondary renal disease: (can lead to the above)
- diabetes most common cause
- Systemic Lupus Erythematosis *
- amyloid
- post- infectious *
- IgA *
Management of nephrotic syndrome
- oedema ✅diuretics (large doses and may need IV if gut oedema), salt and fluid restriction
✅ACE- inhibitors - anti-proteinuric but caution if intravascular deplete or if renal function deteriorating acutely (can get worse)
✅dietary changes/ stains - hypercholesterolaemia (can be atherogenic if LT)
✅treat underlying condition e.g. steroids for minimal change disease
What’s the triad for nephritic syndrome and what are some other features of it?
Triad:
- Haematuria (+/- proteinuria)
- reduction in GFR (renal impairment/ oliguria)
- hypertension
Other features:
Often some proteinuria but less than nephrotic, disruption of endothelium -> inflammatory response and damage to glomerulus, may be acute onset or rapidly progressive (crescentic Gn)
Common causes of nephritic syndrome
Anti- GBM disease (goodpastures) only for rapid progressive
ANCA- associated vasculitis
IgA/ Henoch- Schonlein purpura *
Post- infectious *
Lupus (rare) *
Management of nephritic syndrome
- blood pressure control / reduction of proteinuria
✅ ACE-1 or A11R first line if renal function allows
✅salt restrict
-oedema (less than nephrotic) ✅ diuretics ✅salt and fluid restrict
- disease specific treatments ✅immunosuppressants
E.g. rapidly progressive ✅prednisolone, cyclophosphamide or Rituximab +/- plasma exchange - CVS ✅stop smoking, statin
- dialysis (often short term)
what is ANCA- associated vasculitis? What are some symptoms?
Granulomatosis with polyangiitis (wegener’s) & microscopic polyangiitis
Inflammation of small arterioles and veins
Often kidney & lung
‘Pulmonary-renal syndrome’
Often systemic symptoms (inflammatory condition): fatigue, arthralgia, myalgia, weight loss
Endothelial damage
What is anti-GBM disease (Goodpasture’s)? Symptoms
Caused by anti-bodies to alpha3 chain of type 4 collagen in glomerular basement membrane (can also affect alpha3 chain of type 4 in alveolar BM but harder for anti-bodies to get here)
Pulmonary haemorrhage more likely with pre-existing damage to alveolar endothelium e.g. smokers, infection
Always causes rapid progressive glomerulonephritis - high mortality
Similar presentation to ANCA- associated vasculitis e.g. fatigue/ arthralgia/ myalgia/ weight loss but WITH immune complexes
What is Systemic Lupus Erythematosus?
Auto-immune systemic disease, can affect multiple systems
Many different patterns of renal disease
Can cause nephritic or nephrotic syndrome
What is lupus nephritis?
Inflammation of the kidney caused by Systemic Lupus Erythematosus
Affects mesangial cells - mesangial hypercellularity compresses Bowmans capsule
What are some microscopic features of diabetic nephropathy?
- kimmelstiel - Wilson - nodule (pathognomonic)
- thickened GBM which increases pore size
- mesangial expansion
- glomerulosclerosis (scarring)
- hyaline in arterioles (arteriolosclerosis) (blocks both, in hypertension normally just afferent blocked)
What’s the HbA1c for diabetics?
_<48 mmol/ mol
What is diabetic nephropathy?
commonest cause of ESRD. 30-40% diabetics get ESRD
It’s A glomerulopathy not a glomerulnephritis. Chronic loss of kidney function
‘Diabetic kidney disease’
Pathological changes in diabetic nephropathy
Hyperglycaemia->
- Hyperfiltration/ capillary hypertension (first)
- Glomerular basement m thickening (glycoproteins deposited)
- Mesangial expansion
- Podocyte injury (after BM thickened)
- Glomerular sclerosis/ arteriolosclerosis (last)
Describe how glucose is reabsorbed at the proximal tubules
SGLT2 on apical membrane (3Na+/ glucose symporter)
Maintained by Na pump out (3Na2KATPase) exchanger
GLUT2 on basolateral membrane transport glucose out
How do you get increased GFR in diabetes nephropathy?
Increased NaCl and glucose filtration -> increased reabsorption -> decreased distal delivery of NaCL -> less Na detected by macula dense cells at distal tubule -> afferent arterioles dilate and efferent constricts
Clinical signs diabetic nephropathy
- Increased GFR (hyperfiltration and hypertrophy) Pre 0-5yrs
- Normal albuminuria (latent stage, GBM thickening and mesangial expansion) pre
- Microalbuminuria (variable mesngaila expansion/ sclerosis, increased GBM thickening, podocyte changes) GFR normal incipient DN 5-15yrs
- Overt proteinuria >30 mg/mmol Cr (severely increased albuminuria) systemic hypertension, failing GFR. overt DN 15-25yrs
- ESRD 25yrs+
Yrs of having the disease
What are some other causes for chronic kidney disease that can affect diabetic and non diabetic people?
Hypertension, renovascular (narrowing of renal arteries), other kidney diseases e.g. IgA nephropathy
Diabetic nephropathy risk factors
Genetic susceptibility
Race (Caucasian less likely)
Hypertension
Hyperglycaemia
High level of hyperfiltration
Increasing age
Duration of diabetes (more likely if recently diagnosed)
Smoking
Primary prevention and management of diabetic nephropathy
Tight blood glucose control (<48 mmol/mol) multiple injections/ insulin pump
Tight blood pressure control <130/80 mmHg no particular agent but if microabluminuria angiotensin- Z blocker/ ACE- inhibitor
Not smoking/ exercise/ diet
Inhibition of RAAS - management ( reduces glomerular hyperfiltration, efferent more than afferent, anti-proteinuria effect)
Statin therapy
Moderate protein intake
Maybe SGLT-2 inhibitors future
