Renal Path 2

Question 1

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?

Answer 1

Alport syndrome

Thin basement membrane disease (benign familial hematuria)

Question 2

Inheritance and Manifestations of Alport syndrome

Answer 2

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

Question 3

Electron microscopy findings of alport syndrome

Answer 3

Irregular thickening of basement membrane

Delamination of lamina dense and foci of rarefaction … “moth-eaten” and “frayed” appearance

Question 4

Clinical characteristics of thin basement membrane disease; what causes the thin membrane?

Answer 4

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

Question 5

Does SLE more commonly present as nephritic syndrome or nephrotic syndrome?

Answer 5

60-70% present as Nephritic syndrome

Question 6

Secondary renal diseases that present as nephrotic syndrome (proteinuria)

Answer 6

Diabetic nephropathy
SLE (15% of pts)
Hepatitis C —Cryoglobulinemia (MPGN type I)
HIV nephropathy (FSGS)

Question 7

Secondary renal diseases that present as nephritic syndrome (hematuria)

Answer 7

SLE (60-70% of pts)

Bacterial endocarditis (acute proliferative glomerulonephritis)

Goodpasture (RPGN)

Henoch-Schonlein Purpura (IgA nephropathy)

Question 8

Compared to non-Hispanic whites, what ethnic groups are 1.5-2x more likely to develop diabetes in their lifetimes?

Answer 8

Native Americans
African Americans
Hispanics

Question 9

In the US, _____ is the leading cause of ESRD, adult-onset blindness, and non-traumatic lower extremity amputation d/t atherosclerosis of arteries?

Answer 9

Diabetes mellitus

Question 10

Differentiate type 1 from type 2 DM

Answer 10

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

Question 11

What 2 major processes play key pathophysiologic roles as diabetic glomerular lesions develop?

Answer 11

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

Question 12

Describe histologic features of diabetic nephropathy

Answer 12

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!!

Question 13

Histologic features of advanced renal hyaline arteriolosclerosis

Answer 13

Markedly thickened, tortuous afferent arteriole

Amorphous (thickened) vascular wall

Question 14

Gross appearance of end-stage diabetic kidneys

Answer 14

Overall shrunked kidneys with diffusely granular pitted surface

Marked thinning of renal cortex

May see irregular cortical depressions secondary to pyelonephritis

Question 15

3 renal system lesions prototypical of diabetic nephropathy

Answer 15

1. Glomerular lesions
2. Vascular lesions (principally arteriolosclerosis)
3. Pyelonephritis (including necrotizing papillitis)

Question 16

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

Answer 16

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)

Question 17

What disease is characterized by renal glomerular capillary basement membrane with subendothelial dense deposits (“wire loops”) and deposits present in mesangium?

Answer 17

SLE

Question 18

Clinical features + Histologic changes in diffuse proliferative lupus nephritis

Answer 18

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!

Question 19

Diffuse proliferative lupus nephritis would show mesangial and subendothelial capillary wall ____ localization

Answer 19

IgG

Question 20

What are the 6 patterns of glomerular disease seen in SLE pts? Which one is most vs. least common?

Answer 20

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

Question 21

Most common cause of acute renal failure

Answer 21

Acute tubular injury/necrosis

Question 22

2 most common etiologies of acute tubular injury

Answer 22

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]

Question 23

Primary clinical manifestation of reduced GFR d/t acute tubular injury

Answer 23

Oliguria

Question 24

Patterns of tubular damage in acute tubular injury d/t ischemia vs. toxicity

Answer 24

Ischemic damage:
Patchy necrosis of PCT, PST, and TAL

Toxic damage:
Continuous necrosis of PCT and PST, patchy necrosis of TAL

Question 25

What renal tubular cells are especially susceptible to ischemia?

Answer 25

Proximal tubular epithelial cells are quite susceptible to ischemia, particularly d/t exceptionally high energy requirements (many mitochondria seen on histology)

Question 26

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

Answer 26

True

Question 27

3-phase clinical course of AKI/ARF

Answer 27

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

Question 28

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?

Answer 28

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.

Question 29

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

Answer 29

Chronic pyelonephritis

Question 30

UTI etiologies

Answer 30

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)

Question 31

Pyelonephritis etiology (including predisposing factors)

Answer 31

>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

Question 32

Histological/gross features and complications of acute pyelonephritis

Answer 32

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

Question 33

Hematogenous infection causing acute pyelonephritis is rare; if it does occur, the clinical setting is usually ongoing ____

Answer 33

Sepsis

Question 34

Causes/diseases associated with papillary necrosis

Answer 34

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]

Question 35

2 major entities associated with damage and distortion of renal calyces

Answer 35

Chronic pyelonephritis Analgesic nephropathy

Question 36

VUR with chronic pyelonephritis frequently results in ____ scarring of the kidney

Answer 36

Polar [characteristic scar pattern = broad U-shaped scars at poles]

Question 37

What type of pyelonephritis exhibits large, yellow areas in the kidney and is often associated with Proteus sp.?

Answer 37

Xanthogranulomatous pyelonephritis

Question 38

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?

Answer 38

Fever, eosinophilia, and interstitial renal parenchymal infiltrates May also be complicated by papillary necrosis

Question 39

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?

Answer 39

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]

Question 40

Types/examples of renal vascular diseases

Answer 40

Benign or malignant nephrosclerosis HUS and TTP Renal artery stenosis Atherosclerotic disease Sickle cell nephropathy Diffuse cortical necrosis

Question 41

Define benign nephrosclerosis and its effects

Answer 41

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

Question 42

3 main etiological factors contributing to benign nephrosclerosis

Answer 42

Increasing age —> mild changes HTN —> moderate to severe changes DM —> moderate to severe changes [certain ethnic populations at higher risk = African Americans in US]

Question 43

Pathogenesis of benign nephrosclerosis

Answer 43

Medial and intimal thickening in response to hemodynamic changes, aging, etc. Hyaline protein depositions in arteriolar walls

Question 44

Gross and histologic features of kidney with benign nephrosclerosis

Answer 44

Histology: hyaline arteriolosclerosis, fibroelastic hyperplasia, ischemic atrophy, glomeruli may be spared Gross appearance — somewhat fibrotic/granular surface with tight adherence of scarred capsule

Question 45

T/F: the primary clinical feature of benign nephrosclerosis is renal insufficiency

Answer 45

False — benign nephrosclerosis is not usually associated with renal insufficiency d/t functional reserve of healthy glomeruli

Question 46

Define malignant arteriolosclerosis and its pathologic effects

Answer 46

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

Question 47

Malignant HTN pathogenesis

Answer 47

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

Question 48

Clinical features of malignant HTN as a syndrome

Answer 48

BP = systolic > 180, diastolic > 120 Papilledema Retinal hemorrhage Encephalopathy (early sxs d/t increased ICP) Cardiovascular abnormalities Renal failure

Question 49

What is a potentially CURABLE form of HTN?

Answer 49

Renal artery stenosis

Question 50

Etiologies (including most common cause) of large vessel diseases affecting the kidney, such as renal artery stenosis

Answer 50

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

Question 51

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?

Answer 51

HUS; TTP Consequences include vascular obstruction(s), vasoconstriction, ischemia

Question 52

Pathogenesis and endothelial injury triggers of thrombotic microangiopathies

Answer 52

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

Question 53

Typical vs. atypical HUS classifications

Answer 53

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

Question 54

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

Answer 54

ADAMTS13; neurologic (encephalopathy)

Question 55

Classic features of TTP

Answer 55

Fever Neurologic symptoms (DOMINANT FEATURE) Microangiopathic hemolytic anemia Thrombocytopenia Renal failure in 50% Usually adults <40; more common in females

Question 56

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?

Answer 56

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

Question 57

Signs and symptoms of atheroembolic renal disease (renal infarction)

Answer 57

Flank pain or abdominal pain Hematuria Arterial HTN Arrhythmia Nausea/vomiting Oliguria, anuria

Question 58

What puts the kidneys themselves at higher risk of renal infarction?

Answer 58

High risk is due to quantity of blood flow (25% of cardiac output), “end-organ” vascular supply, and lack of collateral circulation

Question 59

Most renal infarctions are due to ____ d/t mural thrombosis from _____ as the most common source

Answer 59

Embolism; left side of heart [less frequent is vegetative endocarditis, aortic aneurysm, and aortic atherosclerosis]

Question 60

Describe features of sickle cell nephropathy

Answer 60

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