Glomerula Disease Flashcards

1
Q

How does the glomerulus structure change in glomerulonephritis?

A

Narrowed capillary lumen

Subepithelial immune complexes

Increased mesangial cells

Fusion of foot processes

PMN leukocytes present

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2
Q

What is glomerlonephritis? What 4 structures can be damaged from it?

A

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

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3
Q

What are the 4 classifications of glomerulonephritis, give an example of each?

A

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)

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4
Q

What different forms can glomerulonephritis clinically present as?

A
  1. Asymptomatic haematuria &/ or proteinuria - urine dipstick
  2. Chronic glomerulonephritis
  3. Acute glomerulonephritis (has to be nephritic syndrome)
  4. Rapidly progressive glomerulonephritis (often too quick for nephritic syndrome)
  5. Nephrotic syndrome
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5
Q

Describe nephritic and nephrotic syndrome

A

Nephritic syndrome - inflammation disrupting glomerular basement membrane -> haematuria

Nephrotic syndrome - podocyte damage leading to glomerular charge-barrier disruption -> proteinuria

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6
Q

What’s the triad for nephrotic syndrome and what are some other features of it?

A

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

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7
Q

Causes of nephrotic syndrome

A

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 *
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8
Q

Management of nephrotic syndrome

A
  • 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

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9
Q

What’s the triad for nephritic syndrome and what are some other features of it?

A

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)

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10
Q

Common causes of nephritic syndrome

A

Anti- GBM disease (goodpastures) only for rapid progressive

ANCA- associated vasculitis

IgA/ Henoch- Schonlein purpura *

Post- infectious *

Lupus (rare) *

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11
Q

Management of nephritic syndrome

A
  • 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)
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12
Q

what is ANCA- associated vasculitis? What are some symptoms?

A

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

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13
Q

What is anti-GBM disease (Goodpasture’s)? Symptoms

A

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

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14
Q

What is Systemic Lupus Erythematosus?

A

Auto-immune systemic disease, can affect multiple systems

Many different patterns of renal disease

Can cause nephritic or nephrotic syndrome

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15
Q

What is lupus nephritis?

A

Inflammation of the kidney caused by Systemic Lupus Erythematosus

Affects mesangial cells - mesangial hypercellularity compresses Bowmans capsule

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16
Q

What are some microscopic features of diabetic nephropathy?

A
  • 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)
17
Q

What’s the HbA1c for diabetics?

A

_<48 mmol/ mol

18
Q

What is diabetic nephropathy?

A

commonest cause of ESRD. 30-40% diabetics get ESRD

It’s A glomerulopathy not a glomerulnephritis. Chronic loss of kidney function

‘Diabetic kidney disease’

19
Q

Pathological changes in diabetic nephropathy

A

Hyperglycaemia->

  1. Hyperfiltration/ capillary hypertension (first)
  2. Glomerular basement m thickening (glycoproteins deposited)
  3. Mesangial expansion
  4. Podocyte injury (after BM thickened)
  5. Glomerular sclerosis/ arteriolosclerosis (last)
20
Q

Describe how glucose is reabsorbed at the proximal tubules

A

SGLT2 on apical membrane (3Na+/ glucose symporter)

Maintained by Na pump out (3Na2KATPase) exchanger

GLUT2 on basolateral membrane transport glucose out

21
Q

How do you get increased GFR in diabetes nephropathy?

A

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

22
Q

Clinical signs diabetic nephropathy

A
  1. Increased GFR (hyperfiltration and hypertrophy) Pre 0-5yrs
  2. Normal albuminuria (latent stage, GBM thickening and mesangial expansion) pre
  3. Microalbuminuria (variable mesngaila expansion/ sclerosis, increased GBM thickening, podocyte changes) GFR normal incipient DN 5-15yrs
  4. Overt proteinuria >30 mg/mmol Cr (severely increased albuminuria) systemic hypertension, failing GFR. overt DN 15-25yrs
  5. ESRD 25yrs+

Yrs of having the disease

23
Q

What are some other causes for chronic kidney disease that can affect diabetic and non diabetic people?

A

Hypertension, renovascular (narrowing of renal arteries), other kidney diseases e.g. IgA nephropathy

24
Q

Diabetic nephropathy risk factors

A

Genetic susceptibility

Race (Caucasian less likely)

Hypertension

Hyperglycaemia

High level of hyperfiltration

Increasing age

Duration of diabetes (more likely if recently diagnosed)

Smoking

25
Q

Primary prevention and management of diabetic nephropathy

A

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