Theoretical Background

According to Thomas R. Welch (2011) Acute glomerulonephritis (AGN) is a

common condition in childhood. Many children with AGN can be managed in the
primary care setting. The diagnosis is usually made on the basis of urinary findings,
especially the presence of red blood cell casts. One of the most important initial
investigations is determining the complement C3 level; hypocomplementemia is most
characteristic of post streptococcal AGN, while normocomplementemia is most often
seen with IgA nephropathy. Children whose AGN is accompanied by significant
hypertension or renal insufficiency should be assessed by a specialist immediately.

The presence of serious extrarenal signs or symptoms also merits urgent

referral. Otherwise, serial follow-up in the primary care office is appropriate. Particular
attention should be paid to rash, joint discomfort, recent weight change, fatigue, appetite
changes, respiratory complaints, and recent medication exposure.

Proteinuria is also nearly invariant in AGN although any cause of gross

hematuria can lead to some urinary protein. If the urine is not grossly bloody, however,
the combined presence of hematuria and proteinuria virtually always means
glomerulonephritis.

The chronic form may develop silently (without symptoms) over several years. It
often leads to complete kidney failure. Early signs and symptoms of the chronic form
may include:

Blood or protein in the urine (hematuria, proteinuria)

High blood pressure
Swelling of your ankles or face (edema)
Frequent nighttime urination
Very bubbly or foamy urine

Symptoms of kidney failure include:

Lack of appetite
Nausea and vomiting
Tiredness
Difficulty sleeping
Dry and itchy skin Nighttime muscle cramps

It is next important to ascertain any symptoms suggestive of complications of the

AGN. These might include shortness of breath or exercise intolerance from fluid
overload or headaches, visual disturbances, or alteration in mental status from
hypertension.
 Pathophysiology of Acute Glomerulonephritis

The underlying pathogenetic mechanism common to all of these different varieties of

glomerulonephritis (GN) is immune-mediated, in which both humoral as well as cell-
mediated pathways are active. The consequent inflammatory response, in many cases,
paves the way for fibrotic events that follow.
The targets of immune-mediated damage vary according to the type of GN. For
instance, glomerulonephritis associated with staphylococcus shows deposits of IgA and
C3 complement.
One of the targets is the glomerular basement membrane itself or some antigen trapped
within it, as in post-streptococcal disease. Such antigen-antibody reactions can be
systemic with glomerulonephritis occurring as one of the components of the disease
process, such as in systemic lupus erythematosus (SLE) or IgA nephropathy. On the
other hand, in small vessel vasculitis; instead of antigen-antibody reaction, cell-
mediated immune reactions are the main culprit. Here, T lymphocytes and
macrophages flood the glomeruli with resultant damage.
These initiating events lead to the activation of common inflammatory pathways, i.e., the
complement system and coagulation cascade. The generation of pro-inflammatory
cytokines and complement products, in turn, results in the proliferation of glomerular
cells. 
Cytokines such as platelet-derived growth factor (PDGF) are also released, ultimately
causing glomerulosclerosis. This event is seen in those situations where the antigen is
present for longer periods of time, for example, in hepatitis C viral infection. 
When the antigen is rapidly cleared as in post-streptococcal GN, the resolution of
inflammation is more likely.
Structural Changes
Structurally, cellular proliferation causes an increase in the cellularity of the glomerular
tuft due to the excess of endothelial, mesangial, and epithelial cells. The proliferation
may be of two types:
 Endocapillary - within the glomerular capillary tufts
 Extracapillary - in the Bowman space including the epithelial cells
In extracapillary proliferation, parietal epithelial cells proliferate to cause the formation of
crescents which is characteristic of some forms of rapidly
progressive glomerulonephritis.
Thickening of glomerular basement membrane appears as thickened capillary walls on
light microscopy. However, on electron microscopy, this may look like a consequence of
thickening of basement membrane proper, for instance, diabetes or electron-dense
deposits either on the epithelial or endothelial side of the basement membrane. There
can be various types of electron-dense deposits, corresponding to an area of immune
complex deposition, such as subendothelial, subepithelial, intramembranous, and
mesangial.
Features of irreversible injury include hyalinization or sclerosis that can be focal, diffuse,
segmental, or global.
Functional Changes Functional changes include the following:
 Proteinuria
 Hematuria
 Reduction in creatinine clearance, oliguria, or anuria
 Active urine sediments, such as RBCs and RBC casts
This leads to intravascular volume expansion, edema, and systemic hypertension.

Review of Anatomy and Physiology of a Nephron

 The nephron consist of a tubule closed at one end, to form the cup-shaped
glomerular capsule (Bowman’s Capsule), which almost completely enclose a network of
tiny arterial capillaries, the glomerulus. Continuing from the glomerulus capsule, the
remainder of the nephron is about 3 cm long and is described in three parts:

o The proximal convoluted tubule

o Loop of Henle (medullary loop)
o Distal convoluted tubule lead them to collecting duct