Renal Path 2 Flashcards
80% of pts with a family hx of hematuria or recurrent hematuria during childhood have a hereditary form of nephritis. What are the 2 main conditions?
Alport syndrome
Thin basement membrane disease (benign familial hematuria)
Inheritance and Manifestations of Alport syndrome
X-linked inheritance in 85% of cases
Hematuria with progression to chronic renal failure; accompanied by nerve deafness, and various eye disorders including lens dislocation, posterior cataracts, and corneal dystrophy
Electron microscopy findings of alport syndrome
Irregular thickening of basement membrane
Delamination of lamina dense and foci of rarefaction … “moth-eaten” and “frayed” appearance
Clinical characteristics of thin basement membrane disease; what causes the thin membrane?
Characterized by microscopic, asymptomatic hematuria
Renal function is unremarkable and progression to end stage disease is uncommon
Anomaly of thin basement membranes is d/t mutations in genes encoding a3 or a4 chains of type IV collagen
Most pts are heterozygous for the defective gene (carriers); Homozygotes resemble AR Alport syndrome
Does SLE more commonly present as nephritic syndrome or nephrotic syndrome?
60-70% present as Nephritic syndrome
Secondary renal diseases that present as nephrotic syndrome (proteinuria)
Diabetic nephropathy
SLE (15% of pts)
Hepatitis C —Cryoglobulinemia (MPGN type I)
HIV nephropathy (FSGS)
Secondary renal diseases that present as nephritic syndrome (hematuria)
SLE (60-70% of pts)
Bacterial endocarditis (acute proliferative glomerulonephritis)
Goodpasture (RPGN)
Henoch-Schonlein Purpura (IgA nephropathy)
Compared to non-Hispanic whites, what ethnic groups are 1.5-2x more likely to develop diabetes in their lifetimes?
Native Americans
African Americans
Hispanics
In the US, _____ is the leading cause of ESRD, adult-onset blindness, and non-traumatic lower extremity amputation d/t atherosclerosis of arteries?
Diabetes mellitus
Differentiate type 1 from type 2 DM
Type 1 = autoimmune; characterized by pancreatic beta cell destruction + absolute deficiency of insulin. Abs may include anti-insulin, anti-GAD, anti-ICA512
Type 2 = combo of peripheral resistance to insulin action + inadequate secretory response by pancreatic beta cells
NOTE that the long term complications affecting multiple organs are the same for both types
What 2 major processes play key pathophysiologic roles as diabetic glomerular lesions develop?
A metabolic defect linked to hyperglycemia and advanced glycosylation end products produces thickened GBM and increased mesangial matrix
Hemodynamic effects associated with glomerular hypertrophy also contribute to the development of glomerulosclerosis
Describe histologic features of diabetic nephropathy
Markedly thickened tubular and glomerular basement membranes
Diffuse mesangial sclerosis (increased mesangial matrix — leads to narrowing of capillary lumen)
Nodular glomerulosclerosis — nodular appearance is prototypic/characteristic of diabetic glomerulosclerosis!!
Histologic features of advanced renal hyaline arteriolosclerosis
Markedly thickened, tortuous afferent arteriole
Amorphous (thickened) vascular wall
Gross appearance of end-stage diabetic kidneys
Overall shrunked kidneys with diffusely granular pitted surface
Marked thinning of renal cortex
May see irregular cortical depressions secondary to pyelonephritis
3 renal system lesions prototypical of diabetic nephropathy
- Glomerular lesions
- Vascular lesions (principally arteriolosclerosis)
- Pyelonephritis (including necrotizing papillitis)
T/F: DM starts as a macrovascular disease and progresses to affect smaller and smaller vessels at which point it is classified as a microvascular disease
False!
Starts out as a microvascular disease leading to issues like arteriolar nephrosclerosis
Over time and with poor control it becomes a macrovascular disease, affecting larger vessels and leading to complications such as myocardial infarction, renal vascular insufficiency, and cerebrovascular accidents (most common causes of mortality in long-standing DM)
What disease is characterized by renal glomerular capillary basement membrane with subendothelial dense deposits (“wire loops”) and deposits present in mesangium?
SLE
Clinical features + Histologic changes in diffuse proliferative lupus nephritis
Clinically: pts are usually symptomatic with hematuria as well as proteinuria. HTN and mild to severe renal insufficiency are also common
Histology:
Hypercellularity
Glomerulus greatly enlarged, appearing “stuffed” into Bowman’s capsule with resultant decrease in urinary space
Appears almost identical to diffuse proliferative glomerulonephritis seen in post-strep cases — so must correlate biopsy with patient history!
Diffuse proliferative lupus nephritis would show mesangial and subendothelial capillary wall ____ localization
IgG
What are the 6 patterns of glomerular disease seen in SLE pts? Which one is most vs. least common?
Class I: Minimal mesangial lupus nephritis (LEAST common)
Class II: Mesangial proliferative lupus nephritis
Class III: Focal lupus nephritis
Class IV: Diffuse lupus nephritis (MOST common)
Class V: Membranous lupus nephritis
Class VI: Advanced sclerosing lupus nephritis
Most common cause of acute renal failure
Acute tubular injury/necrosis
2 most common etiologies of acute tubular injury
Ischemia — either d/t decreased ECV (hypotension, shock) or diffuse involvement of intrarenal blood vessels in conditions such as malignant HTN; microangiopathies and systemic conditions associated with thrombosis (HUS, TTP, DIC)
Direct toxic injury (drugs, toxins like ethylene glycol/antifreeze)
[uncommon causes include acute tubulointerstitial nephritis or urinary obstruction]
Primary clinical manifestation of reduced GFR d/t acute tubular injury
Oliguria
Patterns of tubular damage in acute tubular injury d/t ischemia vs. toxicity
Ischemic damage:
Patchy necrosis of PCT, PST, and TAL
Toxic damage:
Continuous necrosis of PCT and PST, patchy necrosis of TAL
What renal tubular cells are especially susceptible to ischemia?
Proximal tubular epithelial cells are quite susceptible to ischemia, particularly d/t exceptionally high energy requirements (many mitochondria seen on histology)
T/F: Some necrotic tubular epithelial cells are detached and sloughed off into the tubular lumen as casts that may obstruct urine flow; however some remain as viable, swollen cells that can regenerate
True
3-phase clinical course of AKI/ARF
Initiation: ~36 hours; oliguria
Maintenance: oliguric crisis with evidence of uremia; HYPERKALEMIA
Recovery: large urine volumes (3L/day), large loss of water, Na, K, HYPOKALEMIA, susceptibility to INFECTION
Tubulointerstitial nephritis consists of a group of renal diseases that tend to be insidious — generally characterized by azotemia and decreased GFR as well as the inability to concentrated urine (therefore abormalities in specific gravity: polyuria) and may be acute or chronic.
What are some primary etiologies of tubulointerstitial nephritis?
Infections (acute or chronic like VUR)
Toxins (including acute hypersensitivity interstitial nephritis)
Metabolic disease
Physical factors like chronic obstruction
Neoplasms (association with Bence Jones proteins)
Immunologic reactions
Vascular diseases (like HTN)
Others may include urate nephropathy, hypercalcemia and nephrocalcinosis, bile cast nephropathy, etc.
Recurrent or continuous long-term chronic infection of the kidney with resultant damage to pelvis/calyceal system and parenchyma — resulting in anatomic distortion. May be associated with VUR and/or obstruction
Chronic pyelonephritis
UTI etiologies
Gram-negative bacteria: Commonly E.coli (85%), sometimes Proteus, Klebsiella, or Enterobacter spp.
(most commonly enterics from pts own fecal flora; community acquired more common in females; Lower UTI most common in clinical practice)
Pyelonephritis etiology (including predisposing factors)
> 95% arise via ascending infection from bladder
Predisposing anatomic defect usually present: vesicoureteral reflux and association with intrarenal reflux
Predisposing medical conditions: poorly controlled diabetes; pregnancy, prostate hypertrophy, indwelling catheters
Histological/gross features and complications of acute pyelonephritis
Histology and gross appearance: acute inflammation in tubules with relative GLOMERULAR SPARING; cortical surface with multiple foci of yellow-grey areas of acute inflammation (pus) and abscess formation
Complications: papillary necrosis, pyonephrosis, perinephric abscess
Hematogenous infection causing acute pyelonephritis is rare; if it does occur, the clinical setting is usually ongoing ____
Sepsis
Causes/diseases associated with papillary necrosis
Diabetes mellitus [females more common, usually w/i 10 years of dz, infection in 80%, calcification is rare]
Analgesic nephropathy [usually NSAIDs, females more common, usually takes ~7 years of NSAID abuse, infection in 25%, frequent calcification, almost all papillae affected in different stages of necrosis]
Obstruction [males more common, variable time course, infection in 90%, frequent calcification]
2 major entities associated with damage and distortion of renal calyces
Chronic pyelonephritis
Analgesic nephropathy
VUR with chronic pyelonephritis frequently results in ____ scarring of the kidney
Polar
[characteristic scar pattern = broad U-shaped scars at poles]
What type of pyelonephritis exhibits large, yellow areas in the kidney and is often associated with Proteus sp.?
Xanthogranulomatous pyelonephritis
Acute drug-induced interstitial nephritis may occur as a reaction to many drugs. Analgesic nephropathy is a common example, but in some, this condition may be an idiosyncratic IMMUNE reaction that is not dose-related. What might an immune-mediated acute drug-induced interstitial nephritis exhibit in terms of clinical/lab/biopsy findings?
Fever, eosinophilia, and interstitial renal parenchymal infiltrates
May also be complicated by papillary necrosis
With drug induced tubulointerstitial nephritis, renal function may stabilize or improve with cessation of the drug, but a small percentage of those with analgesic nephropathy may develop what complication?
Urothelial carcinoma of the renal pelvis
[remember that the carcinoma of the pelvis will involve urothelium/transitional epithelium, while carcinoma involving parenchyma is considered adenocarcinoma]
Types/examples of renal vascular diseases
Benign or malignant nephrosclerosis
HUS and TTP
Renal artery stenosis
Atherosclerotic disease
Sickle cell nephropathy
Diffuse cortical necrosis
Define benign nephrosclerosis and its effects
Benign nephrosclerosis is a small vessel disease, and is a general process, not a specific dx
Defined as morphologic changes associated with hyaline sclerosis of the renal arterioles and small arteries
Results in multi-focal ischemia of the kidney parenchyma supplied by the sclerotic vessels
3 main etiological factors contributing to benign nephrosclerosis
Increasing age —> mild changes
HTN —> moderate to severe changes
DM —> moderate to severe changes
[certain ethnic populations at higher risk = African Americans in US]
Pathogenesis of benign nephrosclerosis
Medial and intimal thickening in response to hemodynamic changes, aging, etc.
Hyaline protein depositions in arteriolar walls
Gross and histologic features of kidney with benign nephrosclerosis
Histology: hyaline arteriolosclerosis, fibroelastic hyperplasia, ischemic atrophy, glomeruli may be spared
Gross appearance — somewhat fibrotic/granular surface with tight adherence of scarred capsule
T/F: the primary clinical feature of benign nephrosclerosis is renal insufficiency
False — benign nephrosclerosis is not usually associated with renal insufficiency d/t functional reserve of healthy glomeruli
Define malignant arteriolosclerosis and its pathologic effects
Malignant HTN is a clinical syndrome and medical emergency
Defined as a renal vascular disorder exhibiting injury associated with malignant or accelerated HTN
Pathologic effects: ischemic kidneys, elevated renin, self-perpetuating cycle of damage and HTN, malignant arteriolosclerosis/nephrosclerosis are the tissue analogues/morphologic manifestations
Malignant HTN pathogenesis
Renal vascular damage —> increased permeability of small vessels —> irreversible endothelial injury —> focal vascular death (and focal hemorrhage) —> platelet deposition (and thrombosis) —> FIBRINOID necrosis of arterioles and small arteries —> hyperplastic arteriolitis aka malignant arteriolosclerosis
Clinical features of malignant HTN as a syndrome
BP = systolic > 180, diastolic > 120
Papilledema
Retinal hemorrhage
Encephalopathy (early sxs d/t increased ICP)
Cardiovascular abnormalities
Renal failure
What is a potentially CURABLE form of HTN?
Renal artery stenosis
Etiologies (including most common cause) of large vessel diseases affecting the kidney, such as renal artery stenosis
Most common etiology (70%) = atherosclerosis — atheromatous plaques often at origin of renal a.
Other possible etiology is fibromuscular dysplasia (intimal, medial, or adventitial hyperplasia) — occurs most frequently in younger age group, most commonly young women
Thrombotic microangiopathies include ____ and _____, which are caused by diverse insults that lead to excessive activation of platelets, inducing thrombi in capillaries and arterioles in various tissue beds, including those of the kidney
What are the consequences of these diseases?
HUS; TTP
Consequences include vascular obstruction(s), vasoconstriction, ischemia
Pathogenesis and endothelial injury triggers of thrombotic microangiopathies
Pathogenesis:
HUS = endothelial injury and activation, intravascular thrombosis
TTP = platelet activation and aggregation
Endothelial injury triggers: bacterial toxins (e.g., Shiga-like toxin with O157:H7 E.coli), cytokines, viruses, certain medications, anti-endothelial Abs
Typical vs. atypical HUS classifications
Typical HUS: most frequently associated with diarrhea as a consequence of consuming food contaminated with bacteria producing Shiga-like toxin (E.coli O157:H7); mostly children but adults also at risk. Shigella spp may also be associated
Atypical HUS: non-epidemic and non-diarrheal. D/t inherited mutations of proteins that regulate activation of complement, multiple acquired causes of endothelial injury (chemo and immunosuppressives), mostly affects adults; other causes may include antiphospholipid syndrome, pregnancy, systemic sclerosis, malignant HTN, chemo, and kidney irradiation
Thrombotic thrombocytopenic purpura (TTP) is often associated with inherited or acquired deficiencies of ______, a protease that regulates the function of vWF (via inhibitory autoantibodies); _____ system involvement is usually prominent and plasmapheresis is a tx option
ADAMTS13; neurologic (encephalopathy)
Classic features of TTP
Fever
Neurologic symptoms (DOMINANT FEATURE)
Microangiopathic hemolytic anemia
Thrombocytopenia
Renal failure in 50%
Usually adults <40; more common in females
Atrophy, fibrosis, hemorrhage, and necrosis are dominant histologic features in atheroembolic renal disease (leading to renal infarction)
What are some risk factors of developing this?
Severe atherosclerosis, AAA repair, aortography, intra-aortic cannulization
Afib, mitral valve disease, coronary heart disease, heart failure, cardiac surgery, aneurysm or atherosclerosis of renal arteries
Remember that HEMORRHAGIC renal infarctions are due to renal VEIN thrombosis
Signs and symptoms of atheroembolic renal disease (renal infarction)
Flank pain or abdominal pain
Hematuria
Arterial HTN
Arrhythmia
Nausea/vomiting
Oliguria, anuria
What puts the kidneys themselves at higher risk of renal infarction?
High risk is due to quantity of blood flow (25% of cardiac output), “end-organ” vascular supply, and lack of collateral circulation
Most renal infarctions are due to ____ d/t mural thrombosis from _____ as the most common source
Embolism; left side of heart
[less frequent is vegetative endocarditis, aortic aneurysm, and aortic atherosclerosis]
Describe features of sickle cell nephropathy
Generally hematuria and hypothenuria
Patchy papillary necrosis
30% exhibit proteinuria, usually sub-nephrotic range, but in a small number of cases true nephrotic syndrome occurs associated with progressive glomerulosclerosis
Histologically: diffuse cortical necrosis, coagulative necrosis of both glomeruli and tubules
Grossly: cortex is pale d/t ischemia, angiography shows vascular disruption
Causes include obstetric emergency, septic shock, surgical complication etc. which lead to systemic hypoperfusion or hypoxia
