Chapter 20.2 Tubular and Intersitial Diseases Flashcards
What is acute renal failure (acute kidney injury)??
- Acute decline in renal function (fall in GFR => ↑ BUN/Cr) that is usually reversible.
- Often, results in tubular necrosis.
What are 2 major causes of acute renal failure (acute kidney injury)?
Which is the most common?
- Acute Tubular Injury/Necrosis
- Poor renal perfusion
- Most common: acute tubular injury
Most common cause of acute renal failure/AKI is
Acute tubular injury
-due to acute pyelonephritis
- What is damaged in acute tubular injury?
tubular epithelial cells
What are the 2 most common causes of Acute Tubular Injury?
- Ischemia of the kidneys
- Dierct toxic injury of tubules (drugs/ toxins)
How does the pattern of tubular damage in the proximal tubule and ascending loop of henle seen in acute tubular injury differ between ischemic and toxic sources?
- Both see same amount of casts in same areas, but different patterns of necrosis.
-
Ischemia causes
- Patchy necrosis in proximal tubule and TALoH
- Toxic injury causes
- Continuous necrosis in proximal tubule & patchy necrosis in TALoH
- Both have epithelial casts that occlude the lumen of TALoH (patchy) => DCT => CD
Why are tubular epithelial cells particularly vulnerable to ischemia?
- Increased SA for reabsorption
- High NRG requirements because many mT and need O2
- How will toxicities affect proximal epithelial cells?
- widespread injury, resuling in swelling and vacuolization
In ATI, what occurs to necrotic tubular epithelial cells over time?
Leads to?
Die, slough into lumen of tubule and obstruct urine flow, forming granular casts in tubules that are muddy brown.
Can proximal epithelial cells regenerate?
Yes, as long as the BM is intact
How does ischemic ATI cause necrosis of tubular cells?
- Ischemic ATI => vasoconstriction => decrease in GFR and necrosis of tubular cells
- Vasoconstriction occurs due to loss of tubular cell polarity: Na/K ATPase moves from BL side => luminal side of tubular epithelial cell, pumping Na+ into the urine
- Na+ is sensed by macula densa => triggering vasoconstriction
- => decrease in GFR
Ischemic ATI occurs in what situations?
- hypovolemia, cardiogenic shock, massive bleeding
- Toxic ATI is caused by what drugs and toxins?
- Ethylene glycol (anti-freeze)
- Aminoglycosides
- Heavy medals (e.g. lead)
- Myoglobinuria from crush injury
- Radiocontrast dye
- Urate (e.g. tumor lysis syndrome
What are the 3 stages of the clinical course of AKI/ARF due to ATI and major electrolyte/lab findings in each stage?
Which stage is marked by an increases susceptibility to infection?
-
Initiation– Injury occurs
- Lasts 36 hrs, we see a slight decline or pee (oliguria)
- Maintenance
- Low urine output with uremic features
- Hyperkalemia
- Metabolic acidosis
- Recovery (depends on duration and nature)
- High urine output: polyuria (3L/day) => loss of water, Na, K, hypokalemia
- muscle problems
- Susceptible to infection
What is the prognosis of ATI dependent on?
How likely are these pts to survive?
- Magnitude and duration of injury
- Recovery is typical, some may need dialysis
What is Tubulointerstitial Nephritis
- Group of renal diseases that cause inflammation of renal tubules and interstitium.
- Tubulointerstitial Nephritis is generally characterized by what 2 things?
- Insidious onset
- Azotemia due to decrease GFR, making it difficult to concentrate urine (polyuria and nocturia)
- What are the clinical hallmarks of Tubulointerstitial Nephritis that distinguish it from Glomerular diseases?
- NO nephritic or nephrotic syndrome
- Defects in tubular function –> defect in concentrating urine = polyuria and nocturia
- Salt wasting
- Dimished ability to excrete acids (metabolic acidosis)
- What causes tubulointestinal nephritis?
- 1. Infection: acute, chronic, other
- 2. Toxins
- 3. Metabolic diseases
- 4. Physical factors (chronic obstruction)
- 5. Neoplasm (Bence-Jones proteins)
- 6. Immunological reactions
- 7. Vasular diseases
- 8. Other
Acute Tubulointerstitial Nephritis has what 3 characteristics?
- Rapid onset
- Characterized by
- interstitial edema
- leukocytic infiltration in tubules and interstitium
- Tubular injury
Chronic Tubulointerstitial Nephritis has what 3 characteristics?
- mononuclear leukocytes
- interstitial fibrosis
- lots of tubular atrophy
- How can we tell if it is acute/chronic tubulointerstitial nephritis ?
- If edema is present with eosinophils/neutrophils => acute
- If fibrosis and tubular atrophy => chronic
What is a UTI?
- An infection anywhere along the urinary tract from urethra => renal cortex.
- Can cause tubulointestitial nephritis
85% of UTIs due to what?
Enteric bacteria (e.coli)
What are the most common causes of UTIs?
Gram (-) rods:
- 1. E.coli
- Proteus
- Klebsiella or Enterobacter
- streptococcus faecalis
- staph
What bacteria causes UTIs and produces urease, which can cause struvite kidney stones?
Proetus mirabilis
Most UTIs are ________ infections.
Ascending, from a lower urinary tract infection: urethra => cystitis => pyelonephritis
- _______________ is what allows bacteria to gain access to ureters, while stasis makes it easier
-
Vesicoureteral Reflux (VUR)
- Congenital: malformed or incompetent valve
- Acquired: atony of bladder
What is the Intrarenal Reflux?
- Infected bladder urine d/t VUR => renal pelvis and deep into the renal parenchyma through via tips of the papillae
- Absence of VUR cause what types of infections?
Lower UTI (cystitis and urethertiis): infection remains localized to the bladder.
What is the source of infections in UTI and who are they more common in?
- Patients fecal flora
- Women bc shorter urethra
What type of UTIs do we most commonly see in clinical practice?
Lower UTIs
What is cystitis?
What is it mainly due to?
- Infection and inflammation of the LUT (bladder mucosa)
- 95% due to bacteria (e.coli)
Cystitis is a lower urinary tract that causes what symptoms?
pain with urination (dysuria), frequency/urgency, suprapubic pain, NO systemic symptoms (no fevers, chills, sweats)
Pyelonephritis is an infection of the
kidneys; tubules, interstitium, renal pelvis
Most common cause of clinical pyelonephritis arises from what?
Ascending infection from the bladder
Who is most likely to get pyelonephritis?
Patient with a predisposing anatomic defect: VUR and intrarenal reflex
What are 2 of the common predisposing medical conditions for Pyelonephritis?
1. DM
2. Pregnant people
What is the vesicoureteral reflux?
- Incompetence of the vesicoureteral valve that causes urine to reflux from bladder => ureter => kidney
How can vesicoureteal reflux be acquired in both children and adults?
- Children –> congenital defect (most common) when the intravesical protion of the ureter does not NTR the bladder oliquelym causing a backflow of piss.
- Adults –> obstruction, often due to prostatic hypertrophy
Vesicoureteral reflux can be diagnosed via a ______________.
- What will we see
-
Voiding cystourethrogram.
- Hydronephrosis (Dilated ureter)
Although ascending infection is the most common route of bacteria entering the kidney, they may also do so hematogenously, which is most often occurs in what clinical setting?
Sepsis
Acute Pyelonephritis is acute bacterial infection of the kidney that is almost always the result of
[ascending cystitis infection + predisposing anatomic defect [vesicoureteral junction or obstruction of bladder outlet].
What is a viral pathogen causing pyelonephritis in kidney allografts often leading to the development of nephropathy/allograft failure?
Polyomavirus
Drug and toxin-induced tubulointersitial nephritis is the SECOND most common cause of what?
AKI (acute renal failure)
Acute pyelonephritis is most common in who?
Females from infancy to age 40
What are sx of acute pyelonephritis?
- Sudden onset CVA tenderness
- SYSTEMIC SIGNS – fever and malaise (whereas with cystitis there are no systemic signs)
- WBC Casts
Which has systemic signs: cystitis or acute pyelonephritis?
acute pyelonephritis
What are the morphological hallmarks of Acute Pyelonephritis?
Is the glomerulus affected?
- Patchy interstitial suppurative inflammation
- Aggregates of neutrophils (WBC) in tubules
- Neutrophilic tubulitis
- Tubular necrosis
- Glomerulus is NOT affected
Grossly, what does acute pyelonephritis look like?
multiple foci of areas of yellow-greyish-white acute inflammation (liquefactive necrosis, pus) & abscesses
What complications are assocaited with Acute Pyelonephritis?
- Papillary Necrosis
- Pyonephrosis: pus accumulation in pelvis, calyx, ureter that obstructs kidney
- Perinephric abcess
What is Chronic Pyelonephritis?
chronic tubuloiterstitial inflammation and renal scarring with of the calyces, pelvis and parenchyma.
What are hallmarks of Chronic Pyelonephritis?
- Corticomedullary scaring with blunted/deformed calyces and flattened papilla in upper/lower poles
- Interstitial fibrosis and atrophy of tubules
- Hyaline arteriosclerosis
- Thyroidiization of the kidney: tubules contain eosinophil-protein materal and look like thyroid follicles
VUR w/chronic pyelonephritis à
polar cortical scarring
Xanthogranulomatous Pyelonephritis is a rare form of chronic pyelonephritis associated with ______
proteus
Xanthogranulomatous pyelonephritis is a rare form of chronic pyelonephritis characterized by the accumulation of what?
Associated with what infection?
The large, yellowish orange nodules may be clinically confused with?
- accumulation of foamy macrophages w/ plasma cells, lymphocytes, PMN leukocytes, giant cells
- Proteus infection
- Renal cell carcinoma
*
Chronic Pyelonephritis may develop into ?
FSGS => ESRD
Papillary necrosis is a complication of acute pyelonephritis most often seen in which 4 patients/settings?
- 1) Diabetics
- 2) Analgesic Nephropathy
- 3) Urinary tract obstruction
- 4) Sickle Cell Disease
What is papillary necrosis?
- Coagulative necrosis of renal papillae.
- Sloughing off of the tissue causes gross hematuria that is often painless; renal function is often NL.
What is the M:F ratio for papillary necrosis associated with diabetes mellitus?
Time course?
How do the papillae appear and are they calcified?
- F
- 10 years
- Pale, greyish necrosis of ONLY papilla
What is the M:F ratio for papillary necrosis associated with Analgesic Nephropathy (NSAIDS)?
Time course of abuse?
How does the necrosis appear on the papillae, how diffuse is the necrosis and is there calcification?
- F
- 7 years
- Red-brown necrotic papilla sloughed into calyces with frequent calcification
Which gender has a higher incidence of papillary necrosis as a result of obstruction?
Are calcifications rare or frequent?
- Males
- Frequent
Only what 2 entities causing renal damage affect the calyces,making pelvocalyceal damage an important diagnostic clue?
1) Chronic pyelonephritis
2) Analgesic nephropathy
What is Acute (Drug-Induced) TubuloInterstitial Nephritis?
- Hypersensitivity Type I and 4 reaction to a number of drugs that cause tubulitis and acute renal failure
TUBULOINTERSTITIAL NEPHRITIS CAUSED BY DRUGS (ALLERGIC NEPHRITIS)
Why is it clinically important to recognize drug-induced acute interstitial nephritis?
Withdrawl of the offending drug is followd by recovery, which may take several months
Does Acute (Drug-Induced) TubuloInterstitial Nephritis depend on the dose?
NO
How do drugs cause Acute (Drug-Induced) TubuloInterstitial Nephritis?
- Drugs acts as a hapten until concentrated in the tubules to be excreted in urine.
- Then, they activate IgE and T/B/Plasma cells in the localized area
- What are patients with analgesic nephropathy more likely to develop?
- Urothelial carcinoma of the renal pelvis
NSAIDs have been shown to cause what 2 renal syndromes developing concurrently?
- Acute interstitial nephritis
- Minimal change disease
