Glomerulonephritis (1) Flashcards
Membranous glomerulonephritis
- population profile
- presentation (2)
Membranous glomerulonephritis
- the commonest cause of glomerulonephritis in adults
- presents with: proteinuria or nephrotic syndrome
Causes of membranous glomerulonephritis
- idiopathic
- infections: hepatitis B, malaria, syphilis
- malignancy: lung cancer, lymphoma, leukaemia
- drugs: gold, penicillamine, NSAIDs
- autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid
Management of membranous glomerulonephritis
Management of membranous glomerulonephritis
- immunosuppression: a combination of corticosteroid + another agent such as chlorambucil is often used
- blood pressure control: ACE inhibitors have been shown to reduce proteinuria
- consider anticoagulation
Nephritic syndrome
Basic presentation
Nephritic syndrome
- inflammation of glomeruli
- increased BP
- cola-coloured urine (haematuria)
- Berger’s disease (IgA nephropathy) -> the most common cause of primary glomerulonephritis
- oliguria
Nephrotic syndrome
Nephrotic syndrome
- hypoalbuminemia
- hyperlipidaemia
- peripheral oedema
- massive proteinuria
What’s seen on renal biopsy of membranous glomerulonephritis?
Renal biopsy demonstrates:
- electron microscopy: the basement membrane is thickened with subepithelial electron dense deposits. This creates a ‘spike and dome’ appearance
What is glomerulonephritis (in general)?
Glomerulonephritis
- immune-mediated injury (that affects mainly glomerular tissue)
- inflammation of the glomerulus and other components of the kidney -> inflammation of the nephron
*3rd commonest cause of renal failure in Europe, commonest worldwide
Which part of the kidney does the actual filtration?
- endothelial cells (sitting on basement membrane) -> capillaries
- epithelial cells - podocytes (help in filtration)
- Mesangial cells -> produce collagen and hold capilaries in space
- basement membrane
* all these components can be affected by inflammation
What are the components of the filtration barrier?
Primary vs Secondary glomerulonephritis
- Primary - problem starts in the kidney itself e.g. autoimmune
- Secondary - disease elsewhere in the body, but kidney is injured as a result of that (e.g. SLE -> Lupus nephritis)
Infective vs non-infective glomerulonephritis
(examples)
- infective: HIV, Streptococcal, viruses, bacteria, parasites
- non-infective: minimal change disease, focal segmental glomerulosclerosis, SLE etc. (idiopathic, systemic inflammatory diseases, drugs, malignancy, hereditary, infiltrative disease)
Nephrotic vs Nephritic
- Nephrotic -> problem is about the loss of protein in the urine (hypoalbuminaemia + proteinuria)
- Nephritic -> blood in the urine (haematuria)
Signs of Nephritic syndrome
Nephritic syndrome
- haematuria
- proteinuria (not massive one)
- oliguria
-hypertension
*the above is TETRAD of Nephritic syndrome
HTN - as oliguria and fluid retention
- dysmorphic red cells -> abnormally shaped red cells (as they are squeezed through the filtration barrier - normally not passed through it)
- red cell casts -> RBCs get packed in the renal tubules and casts are formed
Signs of nephrotic syndrome
Nephrotic syndrome
- heavy proteinuria >3.5g/day
- hypoalbuminemia
- oedema
Is it nephrotic syndrome if the proteinuria is less than 3.5 g / day?
No, it must be more than 3.5g/day
3 components that are essential to classify the presentation as nephrotic syndrome
Nephrotic syndrome
- proteinuria of >3.5 g a day
- hypoalbuminemia
- oedema
*all 3 components necessary for classification of nephrotic syndrome
What are different classification of glomerulonephritis (based on structural histological appearance)?
- focal -> if less than 50% of glomerulus is affected
- global -> if the whole capillaries are affected
- segmental -> if part of the capillary bed affected
Focal segmental glomerulonephritis
- what syndrome does it cause
- population presentation
Focal segmental glomerulosclerosis
- cause of nephrotic syndrome and chronic kidney disease
- young adults
- high recurrence in renal transplants
Causes of focal segmental glomerulonephritis
Causes of focal segmental glomerulonephritis
- idiopathic
- secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy
- HIV
- heroin
- Alport’s syndrome
- sickle-cell
Membranoproliferative glomerulonephritis
- what is it known as
- what syndrome does it present as
- what happens
Membranoproliferative glomerulonephritis
- also known as mesangiocapillary glomerulonephritis
- may present as nephrotic syndrome, haematuria or proteinuria
- poor prognosis
Immune deposits in the glomerulus
General pathophysiology of glomerulonephritis
Immune response against the kidney cells - deposition of antigens/antibodies -> inflammation
- Antigen - antibody complex -> start of complement response -> membrane-atack complex produced -> cellular destruction
- chemotaxis factors produced -> neutrophils, cytokines etc -> damaging to the cells
*depends on what parts of the nephron is affected -> different presentation due to different cells being affected
What is the main aim of treatment of glomerulonephritis?
We want to stop the scar to be formed in the glomerulus
*as result of every inflammatory process -> fibrosis and a scar formed (once the scar has formed = no way back)
* if the scar is already formed = sclerosis (scar tissue)
What’s the ‘crescent’?
Crescent
Capillaries are squeezed towards the end -> nephron would not recover
What is the ‘fluffy’/ ‘foam’ urine sign of?
Proteinuria - proteins make urine fluffy
Extrarenal symptoms of glomerulonephritis
*consider different body systems
- Constitutional: fever, weight loss, fatigue
- Eye: uveitis, retinitis
- ENT: sore throat, sinusitis, oral ulcers
- skin: rash
- MSK: arthralgia, arthritis, myalgia
- GIT: diarrhoea, colitis
- Chest: haemoptysis, nodules
- Heart: murmurs, pericarditis
- Nervous system: peripheral neuropathy, seizures
- thrombo-embolic complications
What are the features of uraemia?
Uraemia:
- nausea and vomiting
- alerted consciousness
- chest pain (due to uremic pericarditis)
- anorexia
- metallic taste in the mouth
- rash
- altered sleep pattern
Why does uraemia happen? (in the picture of kidney problems)
uraemia - happens in extreme situation e.g. oliguria -> toxins stay back in the blood (instead of being excreted)
Investigations for glomerulonephritis (1st line)
- urine dipstick -> check for haematuria and proteinuria, SG - if urine is concentrated or dilute
- urine microscopy -> red morphology and casts
- ACR/PCR/24 hr Pr -> to assess a degree of proteinuria
- eGFR, U&E -> markers of kidney function
- FBC and bone profile -> to indicate it is acute or chronic
- CRP and ESR -> acute phase markers
- immunological and serological screen -> look for antibodies
- USS kidney
- kidney biopsy -> definitive way to find out what’s happening inside the kidney
What is the max upper range of protein in a healthy:
- men
- lady
- Men: 2.5/L
- Women: 3.5/L (in pregnancy more is allowed)
Other/extra investigations in glomerulonephritis
- serum C3 and C4 complement levels -> low complement level in the serum as used up for complement response (so inflammation is going on)
- different antibodies: antineutrophil cytoplasmic autoantibodies, anti-glomerular basement membrane (GBM) autoantibodies, antinuclear antibodies, anti-dsDNA antibodies, anti-streptolysin O antibody, anti-DNAse
*different antibodies in different causes of glomerulonephritis
- serology for hep C, hep B, HIV
- serum free light chains and serum immunofixation - myeloma (?)
- blood cultures - to role out infections
What are anti-glomerular basement membrane (GBM) autoantibodies suggestive of?
anti-glomerular basement membrane (GBM) autoantibodies = Goodpasture’s disease
(renal failure + pulmonary haemorrhage
What are anti-nuclear antibodies suggestive of?
antinuclear antibodies = Lupus
Anti- dsDNA antibodies are found in what?
Anti- double stranded DNA antibodies = found in Lupus
Anti-streptolysin O antibody and anti-DNAse antibodies are found in what?
Anti-streptolysin O antibody and anti -DNAse antibodies = post-streptococcal glomerulonephritis
Antineutrophil cytoplasmic autoantibodies are found in what?
antineutrophil cytoplasmic antibodies = in vasculitis
Serum free light chains are found in what?
Myeloma
