Glomerular Flashcards
What major function of kidney?
MAJOR FUNCTION :-
• excretion of waste
• fluid hemostasis (require ADH activity)
• electrolyte hemostasis (require aldosterone, renin)
• hormone and vitamin synthesis – renin, erythropoietin, vitamin D (calcitriol)
Nephron Function: Glomerular and tubular
Glomerular Function : Filtration
Tubular Functions : Reabsorb, secrete , excrete, concentrate urine
Kidney rich with blood supply – receive ~ 25% cardiac output
Glomerular functions:
Glomerular filtrate is ultra filtrate of plasma
which contain similar composition of
plasma except almost free of protein.
Reason: Glomerular basement membrane
provide mechanical barrier to cells (RBC,
WBC) and impermeable to macromolecules
(protein)
Glomerular basement membrane is
permeable to water and low molecular
weight substances.
Tubular functions :
• Almost all glucose , amino acids, potassium, bicarbonate and 75%
of sodium is reabsorbed.
• Sodium reabsorption require Aldosterone
• Water reabsorption require ADH
• Tubular fluid then flows to collecting ducts which is impermeable to
water, but in the presence of ADH water reabsorption will be
increased leading to concentrated urine.
• Thus, if ADH level is low, water reabsorption will be reduced leading
to diluted urine.
• At the collecting duct, sodium is also further reabsorbed by the
action of Aldosterone.
Physiology to pathology:
Any pathological
condition affecting
kidney function can be
manifested by the
abnormalities in the :
•electrolyte and
water hemostasis
•waste excretion
•macromolecule
filtration and
reabsorption.
Pathologic changes of glomerulus:
a) Proliferation of Cells in the Glomerulus
• Mesangial (Phagocytic cells)
• Endothelial–
obliterate capillary
lumen
• Epithelial -
obliterate
Bowman’s space.
b. Infiltration inflammatory cells
- glomerulonephritis
c. Capilary Basement Membrane(BM)
thickening
- increased BM material
- immune complexes deposition
- caused increased glomerular capillary
permeability - PROTENURIA
d. Increased Mesangial Matrix Material
- immune complex dep. in mesangium
e. Epithelial foot process Fusion
- detectable by Electron Microscope
- a result from increased protein leakage
- damage filtration slit
f. Fibrosis
- Global – impaired function
- Caused atrophy and fibrosis of tubules
2 disease in glomerulus:
- Glomerulonephritis (inflammation of glomeruli) by autoimmune and infection
- Glomerulopathy (disease of glomeruli)
Pathogenesis of glomerulonephritis
Immune complex disease
- common cause glomerular injury
- deposition of circulating immune complexes lead to inflammation!
- Immunofluorescence – visible granular deposits
In situ Anti-glomerular basement membrane (GBM) antibody
- deposition of anti-GBM antibody
- glomerular lesions
- immunofluorescence – shows linear deposition of immune complexes
In situ Antigen-antibody complexes (anti non-GBM antibody)
- antigens are not uniformly distributed
- antibody deposition – granular pattern
- example : intrinsic / extrinsic antigen ( drugs / infectious agents)
Types of GN:
A. Minimal change
B. Acute post-streptococcal
Proliferative Glomerulonephritis
(APSGN)
C. Rapidly progressive GN
D. Goodpasture’s syndrome
E. Membranous GN
A. Minimal change
• MOST COMMON NEPHROTIC SYNDROME IN CHILDREN
• loss of BM polyanions
• reduces –ve charge on membrane
• decreased filtration barriers to anionic molecules in plasma – eg. Albumin.
• Common complications : Proteinuria.
• lead to fusion of foot processes (FFP)
• cause – unknown! BUT – mostly related to immunologic attack.
• Pathology : LM and IFM – no abnormality (got the name from). EM –
shows FFP
• Clinical Feature: Proteinuria - LMW anionic proteins.
B. Acute post-streptococcal
Proliferative Glomerulonephritis
(APGN)
Etiology
-After streptococcal infection
-Host antibody target antigen on the
surface of streptococcal
-Induce Type III hypersensitivity and
form immune complexes
-Circulating in blood and can deposit
on BM causing inflammation
-Can lead to glomerular injury
Pathological changes : NEPHRITIC SYNDROME
• enlarged glomeruli due to infiltration of inflammation cells,
proliferation of mesangial cells / matrix and endothelial
cells (hyper cellularity)
• Glomerular basement membrane thickening – increased
permeability to macromolecules and cells – damage
podocyte
• Causing hematuria, proteinuria
• Hypercellularity causing obliteration of capillary and
Bowman space – leading to reduce GFR – oliguria (less fluid
excreted)
• Causing more fluid retention – peripheral edema and
periorbital edema
Clinical Features
• Hypertension, edema, hematuria
• hyperuremia, increased creatinine →
Indicate renal failure!
• elevated serum anti-streptococcal
antibodies
C. Rapidly progressive GN
• known as crescentic GN, rare
• proliferation of epithelial cells in Bowman’s space
• crescent epithelial – irreversible damage –
scarring – severe glomerular disease – renal failure
• Lead to NEPHRITIC SYNDROME
CAUSES:
• Idiopathic
• Immunological injury : Anti –GBM as in Good pasture
• syndrome or due to deposition of immune-complexes as in
autoimmune disorders (SLE) or APSGN.
• Pauci-immune : ANCA (anti neutrophilic cytoplasmic
antibody) in blood.
• Deposition of immune complex on GBM causing
glomerular injury and release of fibrin , red blood cells and
plasma proteins into Bowman space
• This process trigger proliferation of mesangial cells
(monocytes) and parietal epithelial – forming an area of
crescentic shape
• Poor prognosis
• Treatment
• Anticoagulants – REDUCED FIBRIN
• Immunosuppressant & plasmapheresis
• DIALYSIS
• TRANSPLANT
D. Good pasteur’s syndrome
Etiology:
• anti-GBM disease, rare
• Antibody specifically targeting collagen in the basement membrane
• Mostly affecting lung and kidney
• serum +ve for antibody against anti-GBM – immune complexes deposit
Pathology :
• LM- necrosis + fibrosis.
• Immunofluorescence-shows linear Immune Complex along BM.
Clinical features:
• proteinuria , hematuria,
• chronic blood loss- lead to iron deficiency anemia.
E. Membranous GN
•In situ Ag-Ab complexes deposition
• Etiology mostly idiopathic (primary)
or secondary due to auto-antibodies
generated in response to infection,
cancer, medication, autoimmune
disorders
• BM thickening and inflammation
leading to damage GBM
Etiology:
• Primary (Unknown)
• Secondary : SLE, drugs, cancer
Pathological Changes:
• FFP, Immune Complexes deposits, BM thickening.
Clinical Features
• Proteinuria, hematuria
Diabetic nephropathy
Diabetic nephropathy
Hyperglycemia in diabetes mellitus
leads to:
- Glycosuria
- Non-enzymatic glycation of protein
- Glycation of basement membrane of efferent arteriole
leading to hyaline arteriosclerosis – OBSTRUCTION of
blood flow - Initially, there is constriction of the efferent arterioles
and dilation of afferent arterioles - Resulting into glomerular capillary hypertension,
increased in GFR and hyperfiltration at early stage. - This gradually changes to hypofiltration over time.
