Renal Pathology II Flashcards
What is Hereditary Nephritis?
It’s a group of heterogenous familial renal diseases associated with mutations in collagen genes and manifest mostly as glomerular injury.
What 2 diseases are classified as Hereditary Nephritidies?
Alport syndrome
Thin basement membrane disease (benign familial hematuria)
What symptoms predispose many patients (85%) to developing a hereditary nephridity?
Family history of hematuria or recurrent hematuria in childhood
What is the clinical manifestation of Alport syndrome?
Hematuria with progression to CRF, along with:
- nerve deafness
- various eye disorders: lens dislocation, posterior cataracts and corneal dystrophy
What is the progression of Alport syndrome?
Approx. 90% of affected males (X-linked disease) will progress to ESRD by 40 y/o.
What is the pathogenesis of Alport syndrome?
Mutations in genes coding for subunits of collagen IV, which is crucial for GBM, lens and cochlea.
What is the morphological appearance of the GBM on EM in Alport syndrome?
Irregular thickening of BM
Lamination of lamina densa
Foci of rarefraction
*Considered to appear “moth-eaten”
At what age do most patients present with Alport syndrome? What is the major presentation? AT what point does it progress to RF?
Hematuria (gross or microscopic) generally at age 5-20 y/o and renal failure by 50 y/o in men
Thin basement membrane disease’s presentation:
Often ASX with microscopic hematuria. If proteinuria is present, it is mild to moderate.
Thin basement membrane disease is “characterized by…”
Hematuria due to thinned GBM, only approx. 150-250 nm.
What us the progression of Thin basement membrane disease?
Renal function is unremarkable and progression to ESRD is uncommon.
What is the pathogenesis of Thin basement membrane disease?
What is the inheritance (homo- or hetero-)?
Mutations in genes encoding a3 or a4 chains of type IV collagen.
Mostly are heterzygous.
Which systemic diseases can cause secondary renal diseases that present with Nephrotic syndrome? (4)
Diabetic nephropathy
SLE
Hep C (MPGN type I)
HIV nephropathy (FSGS)
Which systemic diseases can cause secondary renal diseases that present with acute nephritic syndrome - or hematuria? (4)
SLE
Bacterial endocarditis (acute proliferative GN)
Goodpasture syndrome
Henoch-Schonlein purpura (IgA nephropathy)
30% of ESRF patients are due to:
Diabetic kidney disease. 40% of DM patients will progress to ESRD.
What are the 2 major processes that play a role in the development of diabetic glomerular lesions?
A metabolic defect linked to hyperglycemia
Hemodynamic effects associated with glomerular hypertrophy
What is the major morphological appearance of diabetic nephropathy? (3 features)
Diffuse capillary BM thickening
Diffuse mesangial sclerosis
**Nodular glomerulosclerosis
How do kidneys appear grossly in end-stage diabetic nephrosclerosis?
Diffuse granular, pitted surface
Marked thinning of renal cortex
Irregular cortical depressions, secondary to pyelonephritis
What are the typical renal system lesions associated with diabetic nephropathy?
- Glomerular lesions
- Vascular lesions
- Pyelonephritis
What is the classic appearance of SLE on EM?
On PAS:
EM:
“Wire loops”
Subendothelial dense deposits that are focal and diffuse
PAS stain:
Increase in cellularity
Glomerular size is enlarged and appears “stuffed” in Bowman’s capsule
Reduced size of urinary space
Henoch-Schonlein purpura
What disease is it related to?
Childhood syndrome consisting of purpura, abdominal pain and GI bleeding, and arthralgias along with renal abnormalities.
IgA nephropathy, because IgA deposits are commonly found in the mesangium.
GN associated with bacterial endocarditis clinically:
On histology:
On immunofluorescence:
Hematuria and proteinuria of various degrees. An acute nephritic presentation is not uncommon, or even progression to RPGN in rare circumstances.
Vary from focal, to global exudative and proliferative, and may have an MPGN pattern.
Glomerular immune deposits.
Microscopic polyangiitis and Granulomatosis with polyangiitis can also cause…
Glomerular lesions
How is Acute tubular injury characterized clinically?
Acute renal failure and often evidence of tubular injury in the form of necrosis of tubular epithelial cells.
What are the 2 major causes of Acute tubular injury?
- Ischemia due to interrupted blood flow. This can be from microscopic polyangiitis, malignant HTN, or microangiopathies.
- Direct toxic injury to the tubules by endogenous (Mb, Hb, Ig, etc.) or exogenous (drugs, contrast, etc.) sources.
Simply put, the pathogenesis in both ischemic and nephrotoxic ATI is believed to be from:
How does each play a role in decreasing urine output and GFR?
Tubular injury and persistent and severe distrubances in blood flow.
Tubular injury causes interstitial inflammation, sloughing of cells and tubular backleak, all of which cause decreased urine output, obstruction and decreased GFR.
Ischemia causes vasoconstrction, which reduces GFR also.
What cells are highly susceptible to ischemia? Why?
Proximal tubular epithelial cells, due to their high energy requirements
Clinical course of Acute tubular injury (3 phases)
It is variable, however 3 phases exist:
Initiation
-oliguria at 36 hrs.
Maintenance
- oliguric crisis w/ uremia
- hyperkalemia often a clinical issue
Recovery
- large urine vol (up to 3 L/day)
- large water, Na+ and K+ loss
- hypokalemia
- susceptibility to infection
What is the prognosis for Acute tubular injury?
Varies, but if the toxin does not cause significant damage to other organs (liver or heart), they can be OK. 95% of those pts. recover.
What toxin is associated with Acute tubular injury?
Ethylene glycol
Tubulointerstitial nephritis is a group of…
What is it “characterized by”?
Group of renal diseases that are insidious and characterized by azotemia and inability to concentrate urine.
It can be acute or chronic.
Etiologies of primary tubulointerstitial nephritis
Infection Toxins Metabolic DZs Physical factors (chronic obstruction, etc.) Neoplasms (Bence-Jones proteins) Immunologic reactions Vascular diseases
Morphologic appearances of acute vs. chronic of tubulointerstitial nephritis
Acute - interstitial edema, leukocyte infiltration and tubular injury.
Chronic - infiltrate of mostly mononuclear leukocytes, prominent interstitial fibrosis and tubular atrophy
85% of UTIs are from:
Other possible bacteria:
Enteric bacteria (E coli)
Proteus, Klebsiella, Enterobacter spp.
95% of cases of cystitis are from:
Inflammation (bacterial) of urinary bladder mucosa
Chronic pyelonephritis definition
Recurrent or continuous long-term chronic infection of the kidney w/ resulting damage to pelvis/calyces and parenchyma that can cause anatomic distortion.
What causes pyelonephritis?
What is a predisposing anatomic defect?
What are predisposing medical conditions?
> 95% arise via ascending infection from the bladder to the kidneys
Vesicoureteral reflux and associated intrarenal reflux
DM, pregnancy
3 major complications of pyelonephritis
Papillary necrosis
Pyelonephrosis
Perinephric abscess
Morphological hallmarks of acute pyelonephritis (4)
Patchy interstitial suppurative inflammation
Intratubular aggregates of neutrophils
Neutrophilic tubulitis
Tubular necrosis
Acute pyelonephritis is almost always the result of:
Ascending cystitis infection combined with a predisposing anatomic defect
What is vesicoureteral reflux?
At the vesicoureteral junction, the ureter is supposed to enter obliquely, but in reflux, there is not an oblique entrance of the ureter, and predisposes pts. to bacteria traveling up the ureters during micturition.
Papillary necrosis cause: DM
M-to-FM ratio:
Time course:
Infection:
Calcification?
M-to-FM ratio: 1:3
Time course: 10 yrs
Infection: 80%
Calcification? Rare
Papillary necrosis cause: analgesic nephropathy
M-to-FM ratio:
Time course:
Infection:
Calcification?
M-to-FM ratio: 1:5
Time course: 7 yrs of abuse
Infection: 25%
Calcification? Frequent
Almost all papillae effected
Papillary necrosis cause: obstruction
M-to-FM ratio:
Time course:
Infection:
Calcification?
M-to-FM ratio: 9:1
Time course: variable
Infection: 90%
Calcification? Frequent
Gross appearance of papillae in DM vs. analgesic nephropathy
DM: pale grayish necrosis limited to papillae
Analgesic nephropathy: red-brown necrotic papillae sloughed into calyces
What percentage of pts. with chronic pyelonephritis did ESRD result?
10-20% required transplant/dialysis, but those numbers are decreasing due to less prevalence of DZ in US
What causes polar scarring of the kidney?
VUR with chronic pyelonephritis
What bacteria is associated with Xanthogranulomatous pyelonephritis?
Proteus spp.
2 most common causes of AKI
- Pyelonephritis
2. Tubulointerstital nephritis induced by drugs/toxins
Clinical representation of Tubulointerstital nephritis induced by drugs/toxins (3)
What can complicate it?
Fever
Eosinophilia
Interstitial renal parenchymal infiltrates
Complicated by papillary necrosis
What is the progression of Tubulointerstital nephritis induced by drugs/toxins?
With cessation of drugs and therapy for infection, renal function can stabilize or improve.
A small percent with analgesic nephropathy may develop urothelial carcinoma of renal pelvis.
Benign nephrosclerosis is a…. instead of a….
General process, not a specific diagnosis
Benign nephrosclerosis definition:
What is the result?
Morphologic changes associated with hyaline sclerosis of renal arterioles and small arteries.
Multi-focal ischemia of the kidney parenchyma supplied by the sclerotic vessels.
Benign nephrosclerosis severity in the following conditions:
Increasing age:
HTN:
DM:
Increasing age: mild changes
HTN: mod-severe changes
DM: mod-severe changes
Pathogenesis of benign nephrosclerosis (2)
Medial and intimal thickening in response to hemodynamic changes, aging, etc.
Hyaline protein depositions in arteriolar walls.
Morphologic changes in benign nephrosclerosis (3)
Hyaline arteriosclerosis
Fibroelastic hyperplasia
Ischemic atropy
What is the progression of benign nephrosclerosis?
Not usually associated with renal insufficiency, but there are some exceptions:
- AAs may have renal insufficiency
- when superimposed on severe HTN
- diabetic nephropathy
Pathologic effects of malignant HTN on the kidneys (2)
They lead to…
Ischemia to the kidneys
Elevated renin
Both lead to a perpetuating cycle of damage and HTN
Malignant arteriosclerosis =
Malignant nephrosclerosis in the kidneys
Hyperplastic arteriolitis is an…
What is it associated with?
Adaptive response of arterioles that are irreversibly injured
Associated w/ renal failure
Gross manifestations of kidneys with malignant HTN
“Flea-bitten” appearance of renal hemorrhages
BP of malignant HTN
180/120
Clinical features of malignant HTN (5)
Papilledema Retinal hemorrhages Encephalopathy CV abnormalities Renal failure
What large vessel disease is possible curable?
What does it resemble?
Renal a. stenosis
Resembles pts. w/ essential HTN
Pathophysiology of unilateral renal a. stenosis lead to… (4)
Stenosis -> renin release -> +RAAS which leads to:
CV hypertrophy
Systemic VC
Increased BV
Renal Na+ and fluid retention
Most common etiology of renal a. stenosis:
What etiology is more common in women?
70% from atherosclerosis
Fibromuscular dysplasia
Thrombotic microangiopathies include clinical syndromes with… (2)
Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS)
What causes TTP and HUS?
Certain triggers cause excessive activation of platelets, including thrombi in capillaries and arterioles in various tissue beds, including the kidneys.
What are the features of HUS and TTP? (3)
What are the consequences of HUS and TTP? (3)
Thrombi in capillaries and arterioles and renal failure
Microangiopathic hemolytic anemia
Thrombocytopenia
Vascular obstructions
Vasoconstriction
Ischemia
Endothelial injury triggers that may cause HUS/TTP (5)
Bacterial toxins Cytokines Viruses Some meds Anti-endothelial Abs
Typical HUS is associated with…
Who does it affect?
What other bacteria can cause it?
Mostly associated w/ diarrhea as a consequence of eating food contaminated w/ Shiga-like toxin (E. coli)
Mostly kids, but can be in some adults.
Shigella spp.
Atypical HUS is associated with…
Inherited mutations of proteins that regulate complement.
Multiple acquired causes of endothelial injury, usually in adults.
Antiphospholipid syndrome, pregnancy, systemic sclerosis, malignant HTN, chemo, kidney radiation, etc.
TTP is caused by…
Involvement of what system is paramount in TTP?
Inherited or acquired deficiencies of ADAMTS13, a protease that regulates function of vWF; leads to unregulated platelets aggregation
Neurologic involvement is prominent in TTP
Classic features of TTP (5)
Who is more likely to get TTP?
Fever Neurological SX** Microangiopathic hemolytic anemia Thrombocytopenia Renal failure (50% of pts.)
Adults <40 y/o; more common in females
Atheroembolic renal disease cause…
SX depend on…
Embolization of fragments of plaques from aorta and renal a. into intrarenal vessels in older pts. w/ atherosclerosis, especially post-op on the aorta, etc.
Clinical SX depend on the number of emboli and pre-existing state of renal function.
What are the SX of Atheroembolic renal disease? (6)
Flank pain Hematuria HTN Arrhythmia N/V Oliguria
Most renal infarcts are due to…
Underlying process is…
Embolism
Mural thrombosis from left heart usually, but can be from endocarditis, aortic aneurysms or atherosclerosis
Sickle cell nephropathy is seen in pts. w/…
What is the presentation?
How many exhibit proteinuria?
The disease and may manifest in pts. w/ sickle trait also.
Generally hematuria and hyposthenuria with papillary necrosis
30% proteinuria that is usually sub-nephrotic range; however, some may progress to full nephrotic syndrome progressing to glomerulosclerosis
What nephrotic process occurs in the kidney diffuse cortical necrosis?
Diffuse cortical necrosis with coagulative necrosis of glomeruli and tubules
What causes diffuse cortical necrosis? (3)
They lead to…
Obstetric emergencies
Sepsis
Surgical complications
… which lead to systemic hypoperfusion or hypoxia
