Pathology of Glomerular Diseases Flashcards
What are the three layers of the glomerulus that fluid filtrates through?
Endothelial layer with fenestrated capillaries
Glomerular Basal Membrane composed of type IV collagen
Epithelial layer composed of filtration slits
What kind of barrier is the glomerular filtration barrier?
Size and charge barrier
How is the glomerular filtrate barrier a size barrier?
Filtration depends upon the size of the molecular
Which molecules are small enough to pass through the glomerular filtration barrier?
Glucose and amino acids
Which molecules are not small enough to pass through the glomerular filtration barrier?
Plasma proteins, red blood cells, white blood cells, and platelets
How is the glomerular filtrate barrier also a charge barrier?
Positively charged ions are filtered more easily compared to negatively charged ones, which are repelled
Why would a kidney biopsy be obtained?
To establish a diagnosis, help guide therapy, ascertain the degree of active and chronic changes
What does the routine evaluation of percutaneous kidney biopsy involve?
Examination of tissue through:
LM
IF
EM
What is the purpose of LM?
It uses H&E, which is the standard stain, as well as special stains to define glomerular structures
What is the purpose of IF?
It localizes and identifies the class of immunoglobulins and complement components
How does IF work?
It is based on the use of specific antibodies which have been chemically conjugated to fluorescent dyes. They bind directly or indirectly to identify the deposition of abnormal molecules and proteins in the tissue
What is the purpose of EM?
To show the presence and precise location of immune complexes
What do immune complexes present as under EM?
Irregular deposits of electron-dense material and other deposits such as amyloid, diabetic changes, structural changes to GBM and podocytes
What are the classifications of glomerular diseases?
Nephrotic Syndrome
Nephritic Syndrome
Asymptomatic hematuria or non-nephrotic proteinuria
Rapidly progressive glomerulonephritis with acute renal injury and rapid loss of renal function
CKD
ESRD
What is the presentation of CKD?
Uremia, increased urea levels in the blood.
What is the management of ESRD?
Requires renal transplantation or dialysis
What are the clinical presentations of nephrotic syndrome? (4)
Massive proteinuria
Hypoalbumenia
Hyperlipidemia
Lipiduria
What is considered massive proteinuria?
> 3.5 g/day
What does hypoalbuminemia lead to?
Massive edema (anasarca)
What causes the proteinuria seen in nephrotic syndrome?
Damage to podocytes, compromised glomerular filtrate barrier –> loss of charge barrier –> proteinuria
Can Nephrotic syndrome be primary or secondary?
Both primary and secondary
Primary (FSGN in adults, minimal change disease in children)
Secondary (systemic process; diabetes)
In which cases can nephritic syndrome present with nephrotic syndrome features?
In severe cases of nephritic syndrome where, there is enough damage to GBM to damage the charge barrier.
What is the pathophysiology of edema in the nephrotic syndrome?
Hypoalbuminemia –> decraese in oncotic pressure –> edema
Decrease in renal perfusion –> RAAS activation –> vasoconstriction –> increase in hydrostatic pressure –> edema
Increase in aldosterone –> Na and H2O retention –> edema
What is the effect of hemoconcentration?
It will trigger osmoreceptors in the brain to secrete ADH –> more water retention –> more edema
What does the decrease in cardiac secretion of natriuretic factors cause?
Exacerbation of edema
How are natriuretic factors secreted?
Through the stretching receptors of the atrium
What are the complications of nephrotic syndrome?
Infections
Arterial and Venous thrombosis
Iron defecinecy anemia
What causes infections to be a complication of NS?
Loss of complement proteins and immunoglobulins in the urine
What is a more common complication, arterial or venous thrombosis?
Renal vein thrombosis
Why is thrombosis a complication of NS? (6)
- Increased urinary loss of endogenous anticogulant antithrombin - III
- Hyperfibrinogenemia from increased synthesis in liver
- Decreased fibrinolysis
- Increased platelet aggregation
- Endothelial changes from hyperlipidemia
- Altered levels of complement proteins
What causes the increased platelet aggregates?
Hyperlipidemia
What causes IDA to be a complication of NS?
Transferrin also might leak in chronic cases
What is nephritic syndrome?
Inflammatory process
What are the clinical presentation of nephritic syndrome?
Hematuria, and RBC casts in urine
Oliguria
Azotemia
Hypertension
Proteinuria with/without edema
Why is there oliguria in nephritic syndrome?
The glomerulus is busy with the inflammation and is not able to the urine
What causes the RBC casts?
RBCs leak and accumulate in the tubule and take the shape of the tubule
What is the difference between proteinuria in NS and nephritic syndrome?
In nephritic syndrome, the protein found in the urine is within the subnephrotic range
What is seen in biopsy of nephritic syndrome?
Hypercellular/inflamed glomeruli
Can the nephritic syndrome be primary or secondary?
Primary and secondary
Primary: post-infectious glomerular nephritis, crescentic glomerulonephritis
Secondary: systemic process; SLE
What can cause abnormalities of the glomerular function?
Damage to major components of the glomerulus, epithelium (podocytes), basement membrane, capillary endothelium or mesangium
What are the mesangial cells?
Extracellular matrix, support cells
What is the main mechanism under most of the primary causes of glomerular disease?
Immune mechanisms
What are some non-immune mechanisms that can also cause glomerular diseases?
Podocyte injury & nephron loss
What is nephron loss?
Nephron will die, the adjacent will proliferate, the fibrosis will spread to the adjacent, and so on
What is the immune mechanism of glomerular injury?
Formation of antibody-antigen immune complexes –> complement activation & leukocyte recruitment
How does neutrophil activation cause glomerular injury?
Release of cytokines, immune activation –> glomerular damage
