L 47-50 Glomerulus 1 & 2 Flashcards
Describe the anatomy of the glomerulus
Note location of the afferent and efferent arterioles, mesangial cells, podocytes, bowman’s capsule, etc.
Where do the tubular capillary bed vessels branch off from?
Tubular capillary beds are derived from efferent arterioles which are the vessels leaving the glomerulus. This means that damage to the glomerulus will have an effect on the blood flow to the cortex and medulla of the kidney.
The medulla is the least perfused and therefore the first to be damaged by alterations in blood flow.
What are the layers of epithelium that line the glomerular capillaries?
The first layer of epithelium is the fenestrated capillary wall called the Visceral epithelium, this is often described specifically as the podocytes
Second layer is the Parietal which lines Bowman’s space, this is the outer layer of the capsule and the filtered contents should not cross this layer
What are the layers that filter the contents of the blood into Bowman’s space?
1) Fenestrated capillary wall
2) Basement membrane
3) Podocytes
Juxtaglomerular apparatus
Juxtaglomerular cells contain the renin and are also called granular cells
Macula densa
Nongranular cells = Lacis cells = extraglomerular mesangial cells
What are the most common causes of glomerular, tubule, interstitial pathology?
Glomerular–immunologic
Tubule/Interstitial–toxic/infectious
Azotemia vs Uremia
Azotemia: elevation of BUN and creatinine, can be prerenal and postrenal
Uremia: azotemia with clinical SSx and biochemical abnormalities
What are the three major renal syndromes?
Acute nephritic syndrome: glomerular, acute; has visible hematuria, HTN, and mild-moderate proteinuria
Nephrotic syndrome: heavy prteinuria (greater than 3.5 gm/day), lipiduria, hypoalbuminemia, edema
Asymptomatic hematuria or proteinuria: mild glomerular abnormalities
What kind of renal failure is described by Oliguria or Anuria with recent onset of azotemia?
This describes acute renal failure
What is polyuria?
Producing abnormally large volumes of dilute urine
Name the 5 Glomerular syndromes
Nephritic Syndrome
Rapdily progressive glomerulonephritis
Nephrotic Syndrome
Chronic renal failure
Isolated urinary abnormalities
What are crescents?
Accumulation of cells composed of proliferating epithelial cells and infiltrating leukocytes
Explain the terminology used in the histology of glomeruli such as:
Diffuse, Global, Focal, Segmental, Mesangial
Diffuse: invlolves all glomeruli
Global: involves the entire glomerulus
Focal: involves only some of the glomeruli
Segmental: involves only part of each glomerulus
Mesangial: primarily the mesangial region
What are the two forms of antibody associated injury to the glomerulus?
1) In-situ immune complex deposition
2) Deposition of circulating immune complex
What type of antibody associated injury could be pictured?
The image has a Granular appearance indicating the antibody associated damage could be a number of things including deposition of circulating complexes or in-situ complexes anywhere except in the BM.
What antibody associated injury is pictured?
The image displays a linear pattern consistent with Anti-GBM Nephritis
Describe anti-GBM Nephritis
Fixed intrinsic normal antigens in the GBM are targeted by antibodies inducing a diffuse, linear, immunofluorescent pattern
The antibodies also cross react with other BM’s in the body, namely those in the alveoli. This is called Good Pasture’s Syndrome
Describe Circulating Immune Complex Nephritis
Ag-Ab complexes from elsewhere in the body lodge in the glomerulus and cause damage when complement gets activated. Antigens may be endogenous like in SLE, or exogenous like bacteria.
Describe Nephritic Syndrom
Hematuria, azotemia, variable proteinurua, oliguria, edema, HTN
Describe rapidly progressive glomerulonephritis
Acute nephritis, proteinuria, acute renal failure
Describe nephrotic syndrome
Greater than 3.5 mg/day proteinuria, hypoalbuminemia, hyperlipidemia, lipiduria
Describe Chronic renal failure syndrome
Azotemia leading to uremia and progressing for months to years
Acute Glomerulonephritis
Also called Acute Proliferative GN (Poststreptococcal, Postinfectious)
1-4 wk after strep infection of skin or pharynx
Morphology: enlarged, hypercellular glomeruli, infiltration of PMNs and monocytes, diffuse changes, tubules have red cell casts
Immunofluorescence: granular deposits of IgG, IgM, C3 in mesangium and along BM
EM: discrete amorphous deposits on epithelial side of BM “humps”
Clinical: child, abrupt onset of malaise, fever, nausea, oliguria, hematuria 1-2 weeks after recovery from sore throat; find red casts in urine, mild proteinuria, periorbital edema, mild to mod HTN
Labs: elevated anti-streptococcal ab titers, low serum C3 (being used up)
Recovery: 95% kids recover completely, adults: 60% recover completely
On light microscopy you see a crescent shape and on immuno you see a linear pattern. Patient also has hemoptysis and periorbital edema. What disease are you thinkning this is?
The linear immuno is indicative of anti gbm
Crescent shape always = Type I Rapidly Progressing GN
The above accompanied with hemoptysis = goodpasture syndrome
Membranous GN morphology
Light Microscopy: diffuse, uniform thickening of capillary wall, silver stain shows spikes of BM between deposits
Immuno: granular deposits of IgG and C3
EM: irregular dense subepithelial deposits that crawl into the BM and make it appear thicker, epithelial foot processes are lost
What disease is the image showing? And what is the major feature being shown?
Image shows uniform thickening of the capillary walls
This is indicative of Membranous GN which is a type of Nephrotic Syndrome
45 y/o Patient presents with mild HTN and hematuria, proteinuria found in the nephrotic range
Immuno shows granular deposits of IgG and C3
EM shows dense subepitheliam deposits
Light microscopy is as shown
What is the condition?
Image shows uniformly thickend membranes of the glomerulus
That combined with EM showing subepithelial deposits that invade the BM and make it appear thicker, and this being a nephrotic syndrome, and an adult indicate this is Membranous GN
Has good outcome thoug many patients will have long-term proteinuria
Young boy presents with edema, lethargy, albuminuria, lipiduria, 4g protein/day
Glomeruli appear normal on light microscopy
EM is as shown below
This is a nephrotic syndrome in a child. The most common cause of this presentation is Minimal Change Disease (Lipoid Nephrosis)
Light microscopy appears normal
Only finding is that of effeced foot processes on EM
What is the disease represented by the image?
Image shows a focal/segmental pattern of sclerosis in the glomeruli
Focal because it is not all the glomeruli, and segmental because it only affects a portion of the glomerulus
Therefore, the disease is Focal Segmental Glomerulosclerosis
What is membranoproliferative GN?
Alterations in BM and proliferation of glomerular cells with leukocyte infiltration
Seen in older children and young adults
Divided into two types, look similar on light micro (large glomeruli, hypercelllar, lobular appearance, GBM thickened, capillary walls appear split (tram track) on silver stain) but different on EM, immuno and pathogenesis of each
Type I: subendothelial deposits, granular on immuno with C3, IgG deposits
Type II: intramembranous deposit, granular with C3, but also linear in BM’s and mesangium, IgG is absent
Patient presents with recurrent hematuria, IgA staining shows up as seen in the image. What is it?
Classic presentation for IgA nephropathy
Describe features of Hereditary Nephritis or Alport syndrome
Hereditary renal disease that affects males more. Defined as a think membrane disease caused by defective GBM synthesis. Accompanied by nerve deafness and various eye disorders.
Clinical: gross or microscopic hematuria, SSx at age 5-20, renal failure in 20-50 years
Renal function is usually normal and prognosis is good
Summarize the prognosis for the glomerular diseases discussed in terms of becoming chronic and leading to potential death
Best outcome: MCD, Poststreptococcal
Intermediate outcome: IgA nephropathy, membranous nephropathy, little worse is membranoproliferative GN
Worst outcome: Crescenteric (RPGN), Focal Segmental glomerulosclerosis
Describe Chronic Glomerulonephritis
This is the end stage of glomerular disease
Morphology: kidneys are symmetrically contracted, hyaline obliteration of the glomeruli, acellular, eosinophilic, PAS positive masses, atrophy of the tubules, interstitial fibrosis, lymphocytic infiltrate
Outside Kidney: uremic state, uremic pericarditis, gastroenteritis, secondary hypoparathyroidism with nephrocalcinosis and renal osteodystrophy, LVH 2nd to HTN
Clinical: Most patients progress insidiously to death, most have HTN with cerebral or CV manifestations, must be on dialysis or recieve transplant
Morphology of diabetic glomerulosclerosis
Capillary BM thickening
Diffuse glomerulosclerosis–PAS positive mesangial matrix deposition
Nodular glomerulosclerosis–Kimmelstiel Wilson disease: spherical, laminated hyaline masses
