Robbins, Chapter 20, Lecture II - tubulointerstitial diseases Flashcards
What am I?
Hearing loss, eye problems (corneal atrophy, lens dislocation), nephritis (micro or macro hematuria and frequently with red cell casts)
Type 4 collagen disorder.
EM=ALTERNATING thickening and thinning of BM, frayed/basket woven/moth eaten
Alport Syndrome
What hereditary nephritis is X-linked?
Alport Syndrome
80% of patinents with family history of hematuria or recurrent hematuria during childhood have one of __what__ disorders?
Defect in type 4 collegen synthesis
Hereditary Nephritis
What are the two types of Hereditary Nephritis?
Which has good prognosis?
Alport Syndrome
Thin Basement Membrane Disease - good prognosis
What am I?
Disease onset at birth, symptoms do not occur until later in life.
Earliest sign is microscopic hematuria detected between 5-20 years. Overt kidney failure between 20-50 years.
Alport Syndrome
Thinning of glom BM confirms dx of what? Asymptomatic hematuria. Type 4 collagen mutation. Most are heterozygous for defective gene >> carriers. Homozygotes resemble AR Alport
Thin Basement Membrane Disease
The following are secondary renal diseases.
Diabetic nephropathy
SLE
Hep C - cryobulinemia (MPGN I)
HIV Nephropathy: FSGN
Do they present with Nephrotic Syndrome or Acute Nephritic Syndrome?
Nephrotic Syndrome
The following are secondary renal diseases.
SLE
BActerial endocarditis - Acute PRoliferative GN
Goodpasture Syndrome: RPGN
HSP: IgA Neph
Do they present with Nephrotic Syndrome or Acute Nephritic Syndrome?
Acute Nephritic Syndrome
What are the consequences of the two major processes play key pathophysiologic roles as diabetic glomerular lesions develop?
Processes:
1. Metabolic defect linked to hyperglycemia
2. Hemodynamic effects associated with glomerular hypertrophy
Consequences: ?
- Advanced glycosylation end products
2. contribute to development of glomeruloSCLEROSIS
What am I? (Based on morphology)
- Capillary BM thickening
- Diffuse mesangial sclerosis - increased mesangial matrix (which then becomes nodular and acellular»_space;)
- NODULAR GLOMERULOSCLEROSIS
Diabetic Nephropathy/Glomerulosclerosis
Clinical course of what?
Systemic HTN»_space; microalbuminuria and elevated GFR»_space; overt PROTEINURIA»_space; ESRF
What can reverse this?
Diabetic Nephropathy/Glomerulosclerosis
Pancreatic transplant can reverse glomerulopathy associated with Type 1 DM
Is (End Stage Diabetic) NEPHROSCLEROSIS a large or small vessels disease?
small vessel
SLE has immune complex deposition of subendothelial or subepithelial dense deposits? (seen on IF)
What do you see on LM?
IF = desposits in SubENDOthelium (and mesangium) LM = "wire loops"
What am I?
Systemic, IgA DEPOSITION IN RENAL MESANGIUM.
Rash on extensor surfaces of arms and legs - lesions contain necrotizing vasculitis with microhemorrhage.
Onset CHILDREN, 3-8yo with excellent prognosis.
Onset often follow respiratory infection.
Henoch-Shonlein Purpura
What am I?
Associated with Multiple Myeloma that produces lytic bone lesions and patients often develop infections with encapsulated bacteria.
Congo Red Positive and Apple Green Polarized Light
Light chain ___ deposited in areas of areas of large bloodflow = INCREASED SERUM PROTEIN LEVELS.
Death due to uremia.
EM = massive BM without deposits
Urinalysis = heavy proteinuria
(amyloid light chain)
Amyloidosis
What am I?
No Congo Red Positive and Apple Green Polarized Light
IF = IgG and C3
Fibrillary Glomerulonephritis
What am I?
Associated with HepC
IgG-IgM compelxes induce vasculitis and membranous GN
Essential mixed cryoglobulinemia
What type of tubulointerstitial disease?
Dirty brown casts in urine, following ischemia
Pathogenesis - ischemia or toxins
Definition - damage to tubular epithelial cells and acutely diminished renal function
Acute Tubular Necrosis
What type of tubulointerstitial disease?
Eosinophilia, rash, fever
Pathogenesis - inflammation
Definition - eosinophilia
Tubulointerstitial fibrosis
What are the two ways that Acute Tubular Necrosis can occur? What part of the nephron does most necrosis occur in each type? Where do casts occur?
(1) Ischemic ATN - PCT, PST, Ascending LoH are all PATCHY
(2) Nephrotoxic ATN - PCT and PST are CONTINUOUS while AscLoH is Patchy
Casts along all patchy parts not necrosed - DCT, CD
Necrotic tubular epithelial cells detach and slough off into tubular lumen - what do these casts cause?
Obstruction of flow!
Clinical course of ATI (3 stages)? What is the largest clinical issue at each stage
(1) Initiation - 36 hours oliguria and rise in BUN
(2) Maintenance - severe oliguric crisis with evidence of uremia. HYPERKALEMIA is the major issue.
(3) Recovery - in a few weeks, initial POLYURIA as water balance is restored. HYPOKALEMIA is clinical problem.
What classifies an oliguric crisis?
40-400mL/day
What is (Primary) Tubulointerstitial Nephritis caused by?
A group of renal diseases that tend to be insidious, generally characterized by azotemia and inability to concentrate urine (resulting in polyuria).
(Gram-negative) E Coli, Proteus, Klebsiella, enterobacter for fecal flora cause what?
Upper or lower infection more common? What sex and age range?
UTI
Lower UTI more common
F>M, 0-40yo
What predisposing anatomic defect usually presents in pyelonephritis?
Is pyelonephritis normally an ascending or descending infection from where? What does scarring look like?
Vesicoureteral reflux (bacteria gains access to ureters from bladder) and association with subsequent intrarenal reflux (each contraction of the bladder = pushes bacteria up >> ASCENDING to kidney from bladder). Polar scarring phenomenon.
What am I? (morphology)
PATCHY INTERSTITIAL SUPPARATIVE INFLAMMATION, *WBC casts on urinalysis, TUBULAR NECROSIS.
In diabetics you see papillary necrosis.
ALWAYS shows FIBROSIS of the underlying renal pelvis and calyces
Acute Pyelonephritis
What am I? (clinical)
Patient comes in SICK with fever, malaise, sudden onset flank pain as costovertebral angle, etc.
POLYOMAVIRUS.
Adult women, due to shorter urethra
Males younger than 1yo - congenital defect
Males older than 40yo - CATHETERIZATION and prostate obstruction
Acute pyelonephritis
Papillary necrosis in acute pyelonephritis:
What three settings?
Male to Female ratio for each.
Length of time for necrosis.
Calcification affects how much of papillae
Color and location of necrosis.
- *See table!!!
(1) DM - F(1:3), 10 years, PALE GRAY necrosis limited to papillae
(2) Analgesic nephropathy (abuse) - F(1:5), 7years, frequent calcification in almost all papillae affected, differnt necrotic stages, RED-BROWN necrotic papilla sloughed INTO CALYX
(3) Obstruction - MALES(9:1), frequent calcification and infection
What am I?
CORTICOMEDULLARY SCARRING OVERLYING DILATED, BLUNTED, OR DEFORMED CALYX.
Caused by recurrent ascending infections, obstructive uropathy, XANTHOGRANULOMATOUS (proteus infection)
Chronic pyelonephritis
What can xanthogranulomatous mimic?
RCC
Inreased scarring in chronic polynephritis can lead to what?
FSGS
What am I?
Fever, rash, eosinophilia, acute renal failure (increased SrCr and oliguria) 2-40 days after exposure to: NSAIDS, synthetic penicillins, or other drugs.
Morphology - see pronounced edema in interstitum and eosinophils/neuts
(Drug associated) Tubulointerstitial Nephritis
What am I?
Small vessel, Hyaline Sclerosis of renal arterioles and small arteries associated with AGING, DM, and HTN.
Sclerosis is due to medial and intimal thickening due to hemodynamic changes. Causes ISCHEMIA of kidney parenchyma.
Benign Nephrosclerosis
What am I?
Morphology - small kidneys with leathery appearance
Clinical - proteinuria, decreased GFR.
What do you have to be careful to look for in african Americans with HTN or Diabetic nephropathy that’s NOT NORMALLY PRESENT?
Benign Nephrosclerosis
Renal insufficiency
In Malignant HTN, what do ischemic kidneys result in elevation of in plasma? This causes abnormal amount of what? What does this ultimately cause?
Renin increased causes abnormal amount of vasoconstriction»exacerbation HTN.
Ultimately causes FIBRINOID NECROSIS and HYPERPLASTIC ARTERIOLITIS, ischemic atrophy, infarct
What are “flea bitten” indicative of?
Renal hemorrhage, gross manifestation of Malignant HTN
What BP classifies as Malignant HTN/medical emergency?
What other clinical features?
200/120
Papilledema, Retinal hemorrhage, ENCEPHALOPATHY, CV abnormalities, early symptoms due to increased ICP
How is HTN due to large (UNILATERAL) renal artery stenosis cured?
Surgery
What are the two most common morphologic etiologies of large vessel disease?
Hint: (1) where do plaques originate (2) strong of beaded appearance
- Most common - ATHEROSCLEROSIS - plaques at ORIGIN OF RENAL ARTERY
- FIBROMUSCULAR DYSPLASIA of the RENAL ARTERY- most commonly in younger women
What are the two thrombotic microangiopathies?
TTP - therombocytopenia, microangiopathic hemolytic anemia, thrombosis
HUS - TTP without neuro symptoms, WITH renal failure
What am I?
Pathogenesis of endothelial injury and activation or from platelette aggregation.
Hemolytic Uremic Syndrome / Thrombotic Thrombocytopenic Purpura
What am I?
Adults who are older younger than 40. F>M
Pentad of symptoms - Fever, NEURO SYMPTOMS, microangiopathic hemolytic anemia, thrombocytopenia (dcreased platelets), renal failure in 50%.
Relapsing and remitting.
Deficient in ADAMTS13.
Classic TTP
What am I?
CHILREN and older adults. Associated with SHIGA-like toxin of E. coli O157:H7. Diarrhea positive, prodrome followed by sudden onset of bleeding, severe oliguria, heamturia, neuro changes, HTN.
Long term prognosis?
Typical HUS
Poor
What am I?
ADULT.
NON-DIARRHEAL, inherited mutation of protein that regulates complement (what % have this?).
SLE/antiphospholipid syndrome, PREGNANCY ASSOCIATED (uncomplicated pregnancy followed by renal failure 3 mo later), systemic sclerosis, chemo, Wegner’s/scleroderma/HTN
Atypical HUS
More than 50% have inherited mutations of proteins that regulate complement.
What makes TTP different from Atypical HUS?
TTP MUST HAVE ADAMTS13 deficiency.
TTP has neuro symptoms, but atypical HUS can too.
What does ADAMS13 protein do? What disease is it associated with?
Protease that cleaves vWF to decrease clotting. vWF accumulates in TTP due to deficiency in ADAMS13 because of presnce of autoantbodies that inhibit ADAMTS13 funciton.
What is elevated in Atherosclerotic Ischemic Renal Disease? A decrease in this (if ACE or ARB are given) will result in what?
ANGII
increased RBF but decreased GFR = actue renal failure
Atheroembolic Renal Disease result from emboli from what location?
Proximal to renal artery
Whath am I?
Flank pain, abd pain, hematuria, arrhythmia, nausea/vomiting, oliguria, anuria, arterial HTN.
Atheroembolic Renal Disease
Renal infarcts are dangerous because the kidney has what? White or red and what shape infarct?
has “end organ” vascular supply with a lack of colalteral circulation.
Infarcts are white and wedge-shaped.
What do the following result in?
Mural thrombosis on the left side of the heart (most common).
Less frequent causes - vegetative endocarditis, aortic aneurysms, aortic atherosclerosis
EMBOLISMS that result in RENAL INFARCT
What am I?
Hematuria, hyposthenuria (DILUTE URINE), patchy papillary necrosis, 30% have sub-nephrotic range proteinuria.
Sickle Cell Neuropathy
What does sickling (due to Sickle Cell Neuropathy) in the vasa recta decrease?
Decreases concentrating ability and increase thrombosis
What am I?
Follow malignant HTN, obstetric emergency, Septic Shock surgery.
Ischemia and necrosis limited to CORTEX (gom and tubules?)»_space; white infarcts.
THROMBOSIS of glom and renal artery, hemorrhage may be present.
Systemic hypoperfusion and hypoxia
Diffuse Cortical Necrosis
???
What are the only two things that affect the calyces?
CPN - reflux nephropathy and chronic obstructive pyelonephritis
Causes of hematuria: SCHITTT
Stones (Nephrolithesis) Congenital Abnormalities (of the bladder) Hematologic abnormalities Infection Trauma Tumor TB
What am I?
Hyalizing arteriolar sclerosis, increasing susceptibility to pyelonephritis and PAPILLARY NECROSIS»_space; causing TUBULAR LESIONS and RBC in urine.
Diabetic Nephropathy
Membranous glom associated with what adenocarcinoma?
Lung
