Nephritic syndrome Flashcards
What is nephritic syndrome and how does it arise?
Nephritic syndrome is a process by which immune complexes arise (antibody-antigen) within the glomerular capillary and initiate an immune response to the glomerular capillary and antigens. Consequently, numerous white cells are recruited. As a result, the filtration membrane becomes inflamed and breaks down which allows RBC’s, WBC’s and proteins to enter the ultrafiltrate. Therefore, the patient presents with haematuria, oliguria (↓ urine output, ↓GFR), ↑ BP, granular casts, sedimentation, pyuria (WBC’s in urine), and proteinuria. The proteinuria can be similar to the protein loss in nephrotic syndrome and can therefore result in similar consequences (↓albumin, ↑lipids, ↓anti-thrombin III, hypercoagulable state, risk of DCT/PE)
What are the causes/types of nephritic syndrome?
- IgA nephropathy*
- Mesangiocapillary GN
- Post-Streptococcal GN*
- Anti-GBM disease*
- Cryoglobulinemia
- Vasculitis
- SLE
What is Anti-GBM disease, how does ti cause nephritic syndrome and how is it treated?
Also known as Goodpasture’s disease, anti-GBM is caused by auto-antibodies to type IV collagen, an essential component of the glomerular basement membrane (GBM). Type IV collage is also found in the lung and pulmonary haemorrhage can occur, especially in smokers. Presents with haematuria/nephritic syndrome, AKI.
Treatment: plasma exchange, steroid +/- cytotoxins
How does IgA nephropathy cause nephritic syndrome?
IgA nephropathy is the commonest type of glomerulonephritis in the developed world and is sometimes known as Berger’s disease. IgA nephropathy occurs when an abnormal IgA antibody forms and deposits immune complexes in the glomerulus. IgA is the main antibody found in breast milk tears, saliva and the mucosal secretions of the upper respiratory tract, gastrointestinal tract and genitourinary tract. Abnormal IgA antibodies are not detected by the body and are therefore not degraded when they become excessive. This allows an accumulation of abnormal IgA to form. The body no longer recognises IgA as self and therefore IgG is stimulated to attack the IgA – together they form immune complexes that become trapped in areas of filtration i.e. the kidney. This stimulates a type III hypersensitivity reaction – inflammation occurs at the site of immune complex deposition (not formation) and the immune complexes specifically deposit in the mesangium (glomeruli). Therefore, inflammation occurs within the glomeruli, allowing pro-inflammatory cytokines and macrophages to damage the mesagnium. This presents with haematuria and proteinuria as large proteins and RBC’s are now able to pass through the damaged glomeruli filtration system and into the urine.
When does IgA nephropathy present and what causes the abnormal IgA antibody formation?
The cause of abnormal IgA antibody formation is unknown, but it is suggested that genetic factors are involved.
IgA nephropathy usually present in childhood as microscopic or macroscopic haematuria and typically presents during infection of the mucosal lining i.e. gastrointestinal infection or respiratory tract infection.
What will microscopy and immunofluorescence show for IgA nephropathy?
Microscopy and immunofluorescence will show evidence of mesangial proliferation (expansion), immune deposits and immune complexes.
Describe another IgA mediated condition that can affect the kidney?
Another IgA-mediated condition is Henoch-Schonlein purpura (HSP) where, unlike IgA nephropathy, other organs are involved; kidneys, skin, connective tissue, scrotum, joints and GI tract.
How is IGA nephropathy treated?
The damage to the kidney is irreversible and therefore treatment is involved preventing further damage.
- Control blood pressure:
• Eat well (reduce salt and cholesterol)
• Anti-hypertensive medications - Prevent immune complex formation:
• Corticosteroids e.g. Prednisolone – prevent production of defective IgA
What causes post-streptococcal glomerulonephritis?
PSGN occurs when the glomeruli become inflamed after a streptococcal infection, most commonly Group A β-Haemolytic streptococci. This group of streptococci has a specific antigen on its surface that causes it to group, hence Group A. The bacteria also produce the enzyme streptolysin which causes lysis of the RBC’s (β -Haemolysis: complete destruction of the RBC). Additionally, these strains are considered nephritogenic strains because they carry the M-protein virulence factor which helps counteract host defences.
An infection with group A β-Haemolytic streptococci bacteria initiates a type III hypersensitivity reaction, where immune complexes are formed (Antibody [IgG and IgM] and antigen). These immune complexes are carried in the blood stream to the glomerulus and become trapped, specifically in the basement membrane and are usually sub-epithelial. These immune complexes initiate inflammation within the glomerulus, which involves activation and deposition of C3 complement, cytokines, oxidants and proteases which all damage the podocytes. The damage to the podocytes allows large molecules to enter the filtrate (RBC’s, Proteins) and causes haematuria, proteinuria, oliguria. This is characteristic of a nephritic syndrome. As well as reduce fluid excreted, there is more fluid retained which results in peripheral oedema and peri-orbital oedema.
Who does PSGN normally affect and when does it occur?
PSGN usually affects children
6 weeks after skin infection e.g. impetigo
1-2 weeks after throat infection e.g. pharyngitis
PSGN is generally mild and spontaneously resolves within a month.
How does PSGN appear on microscopy and immunofluorescence?
Under light microscopy the glomerulus appears enlarged and hypercellular. Under light microscopy the glomerulus has sub-epithelial deposits – ‘humps’. Immunofluorescence lighting shows a ‘starry sky’ appearance, caused by granulation.
How is PSGN diagnosed, treated and complicated?
Blood tests:
- Antibodies against Group A Strep = Anti-DNase B
- Decreased complement
Treatment: is usually supportive
Complications:
Some children will progress to renal failure
Approx. ¼ of adults will develop rapidly progressive glomerulonephritis
What is rapidly progressive GN?
This is the most aggressive GN, with potential to cause ESRF over days. This inflammation ultimately causes cell proliferation in the Bowman’s capsule and forms a crescent-shape. There are different causes, all have the biopsy findings of crescents affecting most glomeruli. This also presents as nephritic syndrome – but indicates very severe disease which if untreated is life-threatening. RPGN, also termed Crescentic Glomerulonephritis (CGN) is a syndrome with glomerular haematuria (RBC casts or dysmorphic RBCs) rapidly developing kidney injury over a few weeks to few months progressing to kidney failure if not treated promptly.
What are the 3 types of RPGN?
- Immune complex disease (45%) e.g. post-infection, SLE, IgA nephropathy, Henoch-Schonlein purpura (HSP)
- Pauci-immune disease (50%)
• No anti-GBM antibodies and no immune complexes.
• Anti-neutrophilic cytoplasmic antibodies (ANCA) are found in the blood (80-90% +ve)
• cANCA is associated with Wegener granulomatosis
• pANCA is associated with microscopy polyangiitis and chug-strauss syndrome - Anti-GBM disease (3%): Goodpasture’s disease
What effect does RPGN have on the glomerulus?
Regardless of the cause, RPGN presents as severe disruption to the filtration membrane and the development of a crescent shape. Typically, because of cell-mediated immunity and macrophage involvement, the GBM breaks. This allows larger molecules (RBC’s, inflammatory mediators plasma proteins and fibrin) to pass through into the Bowman’s space. Following this, more monocytes and macrophages enter the Bowman’s space as well as parietal epithelial cell. The presence of monocytes, macrophages, plasma proteins, fibrin and parietal epithelial cells leads to a thickening of the epithelial layer into a crescent moon shape. Overtime this crescent shape may undergo sclerosis or scarring.
Ultimately the glomerulus becomes damaged and loses the ability to filter blood effectively. This reduces the GFR significantly and if not treated can cause acute renal failure.
