glomerulosclerosis: definition
Secondary changes in the glomeruli due to narrowing of atherosclerotic renal arteries and their branches.
glomerulonephritis: definition
Antibody-mediated disease of the glomeruli.
Polycystic kidney disease: describe the 2 forms
Adult form is autosomal dominant mutation of polycystin (85% -1; 15%- 2) typically presents in age 40-50.
Infantile form is autosomal recessive and causes Potter’s faces (compression due to reduced amniotic fluid volume from fetal anuria).
multicystic renal dysplasia
A relatively benign disease with a unilateral enlarged kidney. Lesions can be removed without consequences, often leaving a normal kidney.
What is the most common developmental kidney disorder?
one-sided renal agenesis (one kidney) or horseshoe kidney (formed by fusion of kidneys at midline).
Occur in 1:800 births.
What are the 3 categories of glomerular diseases?
- Immune-mediated (glomerulonephropathy)
- Metabolic
- Circulatory
What are the 4 clinical syndromes associated with immune-mediated glomerular disease?
- Acute Renal Failure (Crescentic GN, Goodpasture’s)
- Nephritic syndrome (Acute GN, SLE, IgA nephropathy)
- Nephrotic syndrome (Membranous nephropathy, lipoid nephrosis, focal segmental glomerulosclerosis)
- Isolated hematuria (SLE)
Differentiate nephrotic from nephritic syndrome:
Nephrotic: characterized by increased protein (>3.5) in urine, generalized edema, hypoalbuminemia, hyperlipidemia, and lipiduria. NO BLOOD!
Nephritic: characterized by hematuria (with RBC casts), edema, HTN, proteinuria (<3.5), hypoalbuminemia.
What is the clinical significance of transitional epithelium?
It lines the calices, pelves, ureters, urinary bladder, and most of the urethra. It is impermeable to urine and water.
Which portion of the tubule is most susceptible to damage via hypoxia or anoxia?
Proximal tubule.
Uremia: definition
“poisoning with urine” due to renal failure or inability to filter/secrete toxic wastes. It is characterized by retention of water, electrolytes, and nitrogen-rich wastes (measured by blood urea nitrogen – BUN).
Correlate the pathogenesis to the symptoms of autosomal dominant polycystic kidney disease:
A mutation in the gene encoding polycystin-1 (or 2), a cell-cell adhesion molecule. The result is tubular obstruction and the formation of multiple cysts on the kidneys BILATERALLY. Cystic changes impair renal function and cause enlargement of the kidneys.
Most pts. develop renal failure by age 40-50
What is multicystic renal dysplasia?
In contrast to ADPKD, multicystic renal dysplasia is usually unilateral and the lesions can be removed without consequence.
List the important metabolic glomerulopathies:
Diabetes and Amyloidosis
Explain how circulatory disorders affect the glomeruli:
- Atherosclerosis of the renal arteries causes hypoperfusion leading to involution and hyalinization of the glomeruli.
- Sudden onset HTN (malignant) causes fibrinoid necrosis of the glomerular capillaries.
- DIC- formation of microthrombi in the glomerular capillaries.
Explain the pathogenesis of acute glomerulonephritis (AGN) and correlate the pathologic and clinical findings:
immune-mediated inflammatory glamerulopathy that occurs 1-2 weeeks after an acute infection (usually strep), and is common in children. Antigen-antibody complexes accumulate in the glomeruli and recruit inflammatory cells and complement.
Histologically the glomeruli are hypercellular, with fusion of foot processes, narrowed capillaries, and increased numbers of mesangial cells and PMNs. Immunofluorescence reveals subepithelial immune complexes (humps).
Clinically patients present with oliguria, murky brown urine, edema (esp periorbital–due to Na retention), headache, somnolence.
Labs show a nephritic syndrome (blood, albuminuria), elevated renin.
Explain the pathogenesis of crescentic glomerulonephritis and relate the pathologic and clinical findings:
Crescentinc glomerulonephritis usually occurs after focal necrosis of glomerular capillaries, as can occur in Goodpasture’s syndrome (anti-collagen IV), Wegener’s (anti-neutrophil cytoplasmic antigen), or in polyarteritis nodosa and poststreptococcal glomerulonephritis.
Pathogenesis is formation of an exudate in bowman’s space. Macrophages are replaced by fibroblasts which lay down collagen causing fibrosis and ultimately destruction of the glomerulus.
Clinically, this results in nephritic syndrome, oliguria or anuria, and rapidly progressive glomerulonephritis (RPGN) - this is Acute Kidney Failure.
Explain the pathogenesis of membranous nephropathy and relate the pathologic and clinical findings:
Immune-mediated and characterized by diffuse thickening of the glomerular basement membranes secondary to accumulation of immune complexes. Usually complexes are idiopathic, but can be complexes from tumor, drugs, or infection (hepB, treponema pallidum).
Histologically glomerulii have thickened basement membranes, but are normocellular. Immunofluorescence reveals even, granular deposits of IgA and C3 throughout basement membrane.
Clinically patients present with NEPHROTIC syndrome (no evidence of inflammation). Prognosis is rule of 1/3.
How is lipoid nephrosis diagnosed?
AKA minimal change disease. Pt. (usually a child) will present with NEPHROTIC syndrome. Tx presumably with corticosteroids. If it responds, it’s minimal change. If it doesn’t, get a biopsy. It’s probably FSG.
Light microscopy is normal. Immunofluorescence is negative. EM will show fusion of foot processes.
Focal segmental glomerulosclerosis: differentiate primary from secondary.
Primary: nephrotic syndrome of kids. Clincially not distinguishable from minimal change, but will not respond to steroids.
Secondary occurs in obese people, those with Sickle Cell, and those with HIV (worst prognosis).
Focal- affects less than half of glomeruli. Segmental- only some capillaries in affected glomerulus are scarred.
What do most forms of chronic proliferative glomerulonephritis have in common?
it is essentially the progression of other nephrotic or nephritic syndromes including IgA nephropathy, FGN, and especially SLE glomerulonephritis.
They all have a chronic course, don’t respond to treatment (except SLE which responds to steroids), and slowly but inexorably lead to ESRD.
What is the cause of end-stage kidney disease and how does it present clinically?
It is the progression of any glomerulopathy resulting in widespread fibrosis and destruction of glomeruli. Grossly, kidneys are shrunken bilaterally with granular surface. Histology shows hyalinization of glomeruli and tubular atrophy.
How does diabetes mellitus affect the kidneys?
Deposition of glucose in the lumen of the arterioles causes hyalinosis, thickening of the vessel wall, and narrowing of vascular lumen. This ultimately leads to ischemia and tubular atrophy, along with activation of the RAA. Ultimately this can cause papillary necrosis and post-renal disease.
The glomerular basement membrane thickens and there is hypertrophy of the mesangial matrix.
DM pts are also susceptible to pylonephritis.
List the 4 most common forms of kidney stones:
- Calcium stones (75%- associated with hyperexcretion of Ca, often inherited)
- Struvite stones (15%- complication of UTI, larger and more irregular, can fill whole renal pelvis)
- Uric acid stones (5%- most pts. have gout, not all though).
- Cystine stones (1%- associated with rare genetic conditions).
