Acute Glomerulonephritis Flashcards
What is Glomerulonephritis?
Glomerulonephritis means inflammation of the glomeruli
Glomerulonephritis (GN) is a spectrum of renal diseases of varied etiology and clinical presentations that are characterized by clinical and histological evidence of glomerular damage.
GN are mostly immunologically-mediated and also largely respond to immunosuppressive therapy.
GN is an important cause of both acute and chronic kidney diseases worldwide
GN is a leading cause of ESRD in Africa, while in developed countries, it ranked 3rd (after DM and HTN)
Basic anatomy of the kidney (location, weight, dimensions and structure)
A paired organ located retroperitoneally Weight = 120-200g
Dimensions –vertical – 10 to 14cm
transverse – 5 to 6cm
anteroposterior – 3 to 4cm
STRUCTURE OF THE KIDNEY:
Outer cortex
Inner medulla
What is a Nephron? How many nephron per kidney? What do they consist of?
- functional unit of the kidney
- each kidney has about a million nephrons
- Each nephron consists of – renal corpuscles, proximal and distal convoluted tubules, loop of Henle, and terminally, the collecting ducts.
The renal corpuscle is made up of:
glomerulus
bowman’s capsule
What is the Glomerulus?
a tuft of capillaries surrounded by bowman’s capsule, serves as the filtration barrier. It filters the blood based on particle size and charge.
The glomerular tuft is held together and regulated by mesangial cells. It allows filtrate from plasma to move into the urinary (Bowman’s) space
Discuss the The filtration barrier of the glomerulus
Filtration of molecules across the barrier depends on what?
The filtration barrier is composed of:
1. Fenestrated endothelium
2. Glomerular basement membrane
3. Podocytes and their foot processes
Filtration of molecules across the barrier depends on:
*Hydrostatic pressure difference
*Size of the molecule
*Charge on the molecule
Whar are the types of Glomerular diseases?
- Focal: some, but not all, glomeruli show the lesion
- Diffuse (global): most of the glomeruli (>75%) contain the lesion
- Segmental: only a part of the glomerulus is affected (most focal lesions are also segmental, e.g. focal segmental glomerulosclerosis)
- Global: all of the glomerulus is symmetrically involved
- Proliferative: an increase in cell numbers due to hyperplasia of one or more of the
resident glomerular cells with or without inflammation - Membrane alterations: capillary wall thickening due to deposition of immune deposits or alterations in basement membrane
- Crescent formation: epithelial cell proliferation with mononuclear cell infiltration in Bowman’s space
How can Glomerular diseases be classified?
Aetiology: primary or secondary
According to period: acute or chronic
Histologic pattern: focal, diffuse, segmental or global
Number of cells: non-proliferative or proliferative
Immunofluorescence: Immune or pauci-immune
Primary cause of glomerular diseases?
- Minimal change disease (MCD)
- Membranous nephropathy
- Focal segmental glomerulosclerosis
- Mesangiocapillary GN now called Mesangioproliferative GN
What are some secondary causes of glomerular disease? Give examples under each
- Medications: NSAIDs, pamidronate, rifampicin, gold, lithium, interferon alpha.
- Allergens: Pollens, serum sickness, vaccines, bee sting
- Infections
Bacterial: Endocarditis, syphilis, tuberculosis, mycoplasma infections
Viral: HIV, HBV, HCV, EBV, CMV, VZV
Protozoal: Toxoplasmosis, malaria
Helminthic: Schisostomiasis, trypanosomiasis, filariasis
Systemic illnesses: Systemic lupus erythematosus (SLE), Rheumatoid polyarthritis, amyloidosis, Henoch-Schonlein purpura, ANCA positive vasculitis. - Neoplasia: Solid tumours, Haematological malignancies (lymphomas, leukaemias), Multiple myeloma
- Metabolic diseases and heredofamilial: Pregnancy-associated, Chronic allograft failure, Obesity
- Miscellaneous:Pregnancy-associated, Chronic allograft failure, Obesity
What is the Clinical presentation of GN?
- Asymptomatic urinary abnormalities (proteinuria / Or haematuria)
Proteinuria, accompanied by variable degrees of hematuria, is the hallmark of glomerular disease. - Nephrotic syndrome
- Nephritic syndrome (Acute glomerulonephritis)
- Nephritic-Nephrotic syndrome
- Systemic Hypertension
- Rapidly progressive GN
- Acute kidney injury
8.Chronic kidney disease-CKD/ ESKD
Nephrotic syndrome is characterized by
- Proteinuria >3.5g/day
- Hypoalbuminemia
- Dyslipidaemia
- Generalized oedema from salt and water retention
How do you investigate glomerular disease?
Urine microscopy: Red cells, red-cell casts
Urinary protein: Nephrotic or sub-nephrotic-range proteinuria
Serum urea: May be elevated
Serum creatinine: May be elevated
Culture (throat swab, discharge from ear, swab from inflamed skin): Nephritogenic organism (not always)
Antis treptolys in-O titre: Elevated in post-streptococcal nephritis
C3 and C4 levels: May be reduced
Antinuclear antibody (ANA): Present in significant titre in systemic lupus erythematosus
Antinuclear cytoplasmic antibody (ANCA): Positive in some vasculitides
Anti-glomerular basement membrane (anti-GBM): Positive in Goodpasture syndrome
Cryoglobulins: Increased in cryoglobulinaemia
Chest X-ray: Cardiomegaly, pulmonary oedema (not always)
Renal imaging: Usually normal
Renal biopsy: Any glomerulopathy
What are the causes of nephrotic syndrome
Primary:
Minimal-change nephropathy
Congenital nephrotic syndrome
Focal segmental glomerular sclerosis
Membranous nephropathy
Secondary:
Amyloidosis
Diabetic nephropathy
What is the Management of Glomerular disease?
General measures
Dietary sodium restriction
Diuretics
Nephrotic patients may malabsorb diuretics (as well as other drugs) due to gut mucosal oedema
Normal protein diet is advisable. A high-protein diet increases proteinuria and can be harmful in the long term.
Albumin infusion produces only a transient effect. It is only given to patients who are diuretic-resistant
Anticoagulation
Antibiotics if Sepsis.
Statins
ACE inhibitors and/or angiotensin II receptor antagonists
What are some Specific measures to take in the Management of Glomerular disease?
Immunosuppressive agents: corticosteroids, calcineurine inhibitors (tacrolimus, cyclosporine), cyclosphosphamide
Treat the underlying cause
What is ACUTE GLOMERULONEPHRITIS aka nephritic syndrome?
What is it characterized by?
Acute glomerulonephritis is an inflammation of the renal parenchyma due to immune complex deposition, characterized by:
- Sub-nephrotic range proteinuria (1–2 g/24h)
- hematuria with red blood cell casts,
hypertension, - oliguria (Acute renal failure) and fluid retention.
It is not a disease itself, but the manifestation of an underlying disease
Discuss the aetiology of ACUTE GLOMERULONEPHRITIS
A) Post infectious
Bacterial eg Group A ß hemolytic streptococci (Post- streptococcal GN), staphylococcus , Pneumococcus ,Salmonella, Legionella
Viral eg Hepatitis B, Hep. C , infectious Mononucleosis
Parasites eg Toxoplasmosis, Malaria, Shistosomiasis
B) GN of undetermined etiology
* Membranoproliferative GN
* Rapidly progressive GN
C) Connective tissue diseases
* SLE
* Henoch Schonlein Syndrome
* Polyarteritis Nodosa
D) IgA nephropathy
E) Familial Nephropathy eg Alport Syndrome
F) Others eg Shunt Nephritis, Infective Endocarditis, Visceral abscess
What is Post-streptococcal glomerulonephritis?
What is it caused by? What is it’s latency period?
Post-streptococcal glomerulonephritis (PSGN) is the most common form of acute GN, usually occurs in childhood.
Usually caused by nephritogenic strains of streptococcal infection (group A β-haemolytic streptococcus), pharyngitis or impetigo.
The latency period from infection may vary from 1 to 2 weeks after pharyngitis to 3 to 6 weeks after skin infections.
What is the Pathophysiology of Post-streptococcal glomerulonephritis?
- Inflammation of glomerulus damages the glomerular capillary
- Porous basement membrane allows rbc’s to leak out causing hematuria, thank can stick together in the renal tubule causing rbc casts
- Damaged podocytes results in proteinuria <3.5g
- Due to inflammation in the glomerulus wbc such as neutrophils are recruited to the area and leak through the capillaries causing sterile pyuria because there’s no infection
- The inflammation also reduces GFR , therefore reduces fluid passing through resulting in oligouria and AKI wm
- RAAS is stimulated causing HTN
Post streptococcal GN Follows infection of throat or skin with
Group A ß hemolytic streptococci (usually 1- 4 weeks)
Common strains 12 , 4 , 1 with Pharyngitis
Type 49 with Pyoderma
Mainly involves school age boys
Is an Immune-Complex Disease.
The antibody formed against streptococcus combines with antigen and forms Immune complex
Immune complex deposition along the capillary wall
Activate complement
Inflammatory changes
Glomerular injury
Pathology of Post-streptococcal glomerulonephritis on light microscopy
Glomeruli are enlarged, hypercellular ,ischemic capillary loops narrowed
Hypercellularity due to Infiltration by leucocytes , both neutrophils and monocytes; Proliferation of endothelial and mesangial cells
In severe cases by crescent formation
Swelling of endothelial cells along with proliferation leucocytic infiltration obliterates the capillary lumen
There may be interstitial edema.
Tubules often contain red cell casts
Pathology of Post-streptococcal glomerulonephritis with Immunofluorescence staining
Granular deposits of IgG , IgM , C3 along the capillary walls basement membrane
Pathology of Post-streptococcal glomerulonephritis on an Electron Microscopy
Discrete, amorphous, electron dense deposits on the subepithelial side of capillary basement membrane often shows Lumpy deposits (Subepithelial humps).
What is the gold standard to test for Post-streptococcal glomerulonephritis?
Renal biopsy
CF and atypical presentation of Post-streptococcal glomerulonephritis
Most commonly affects children and young adults
Sudden onset of hematuria, with RBC casts in the urine
Proteinuria
Hypertension
edema
urine is smoky, cola-coloured
Impairment of renal function
Atypical presentation
convulsions due to hypertensive encephaclopathy
left ventricular failure (Acute pulmonary edema)
Acute renal failure
