Kidney: Diseases Affecting Tubules and Interstitium Flashcards
What are the most common forms of tubular injury that also involve the interstitium?
Inflammatory diseases
Acute Tubular (Kidney) Injury
What is the example of inflammatory tubular injury?
Tubulointestinal nephritis (pyelonephritis)
What are the types of acute tubular (kidney) injury?
Toxic
Ischemic
What is tubulointerstitial nephritis?
Inflammatory disease of the kidneys affecting the interstitium and tubules
What happens during the late course of the tubulointerstitial nephritis?
The glomeruli may be affected
What are the causes of tubulointerstitial nephritis?
Mostly by bacterial infection with pelvis involvement: pyelonephritis
What is the term interstitial nephritis used for?
Typically for non-bacterial origin
What are examples of non-bacterial origins of interstitial nephritis?
Drugs
Metabolic Disorders; hypokalemia
Physical Injury; irradiation
Viral Infections
Immune reactions
Can TNI and IN be acute and chronic?
Yes can be both acute or chronic regardless of etiology
What is acute pyelonephritis?
SUPPURATIVE inflammation of kidney and pelvis
What usually causes acute pyelonephritis?
Examples?
Bacteria; E. coli, Klabsiella, Proteus, Enterobacter, Pseudomonas
What are the typical manifestations of acute pyelonephritis?
Same as typical manifestations of UTIs
What is acute pyelonephritis associated with?
Lower UTI
Less commonly associated with upper UTI
What are examples of lower UTIs?
Cystitis, prostatitis, uretheritis
What are examples of upper UTIs?
Pyelonephritis (pelvis and kidneys)
What is the route of infection of acute pyelonephritis?
- Lower urinary tract –> ascending infection
- Through the bloodstream –> hematogenous infection
What is the pathogenesis of acute pyelonephritis? (4)
- Distal urethra: adhesion of bacteria to mucosal surfaces, followed by colonization through fimbriae
- Bladder: expansive growth of the colonies & moving against the flow of urine (obstruction, diabetes)
- Ureters: incompetence of the vesicoureteral orfice, resulting in vesicoureteral reflux (VUR). Allows for bacteria to ascend to ureter into the pelvis
- Pelvis: pyelonephritis
How do the bacteria ascend from the contaminated bladder urine (acute pyelonephritis)?
Along the ureters
What is VUR?
Can either be a congenital defect that results in incompetence of the ureterovesical valve
OR
Acquired in persons with a flaccid bladder
How does acquired VUR result?
From spinal injury or with neurogenic bladder dysfunction secondary to diabetes
What can lead to seeding of the kidneys and thus acute pyelonephritis?
Septicemia
Infective endocarditis
What are the predisposing factors for acute pyelonephritis? (9)
- Urinary Obstruction
- Instrumentation of the UT
- Vesicoureteral reflux
- Pregnancy
- Female gender
- Male gender and age
- Pre-existing renal lesions
- DM
- Immunosuppression and immunodeficiency
How is urinary obstruction a predisposing factor of acute pyelonephritis?
Results to stasis –> facilitates bacterial growth
How is male gender and age a predisposing factor of acute pyelonephritis?
As a result of the development of prostatic hyperplasia, which causes urinary outflow obstruction
Why are pre-existing renal lesions a predisposing factor for acute pyelonephritis?
Causes intrarenal scarring and obstruction
How is DM a predisposing factor for acute pyelonephritis?
This leads to infection and bladder dysfunction
What are the gross features of acute pyelonephritis?
One or both kidneys may be involved
The affected kidney may be normal in size or enlarged
Characteristically, discrete, yellowish, raised abscesses are grossly apparent on renal surface
What are the histological features of acute pyelonephritis (primary)?
Patchy interstitial purulent (consisting of pus)
Tubular destruction in the involved area
Neutrophilic casts in collecting ducts –> pyuria
Where do the neutrophil casts in the urine originate from (primary AP)?
Distal renal tubules and collecting ducts (distal nephron)
What is the second form of AP?
Necrosis of the renal papillae (papillary necrosis)
What are the predisposing conditions to the second form of AP?
Diabetes
UT obstruction
Sickle cell anemia
What are the gross features of second form of AP?
Gray-white to yellow necrosis of the apical 2/3 of the pyramids
One or several papillae may be affected
What are the microscopic features of second form of AP?
The papillary tips show characteristic coagulative necrosis, with surrounding neutrophilic infiltrate
Coagulative necrosis rimmed by acute inflammation
What are the clinical manifestations of AP?
- Sudden pain at the costovertebral angle !!
- Evidence of infection
- Localizing UT signs of dysuria, frequency, and urgency
- Urine appears turbid
- Predisposing factors
What causes the turbid appearance of the urine?
The pus (pyuria)
What are the predisposing factors preset in the clinical course of AP?
The disease may become recurrent or chronic
The development of papillary necrosis
What is the prognosis like if there is papillary necrosis?
Poor prognosis
What are the clinical manifestations that indicate infection?
Fever
Chills
Malaise
What is chronic pyelonephritis?
Interstitial inflammation and scarring of the renal parenchyma followed by the deformity of the pelvicalyceal system in patients with a history of UTIs
What are the two forms of chronic pyelonephritis?
- Chronic obstructive
- Chronic reflux-associated pyelonephritis (reflux nephropathy)
What is the pathogenesis of chronic obstructive pyelonephritis?
Obstruction predisposes kidney to infection
Recurrent infection is superimposed on obstructive lesions, leading to recurrent bouts of renal inflammation and scarring
Does chronic pyelonephritis affect one or two kidneys?
It can be unilateral or bilateral
If CP is bilateral which regions of the kidneys are affcted?
Posterior urethral valves
If CP is unilateral which regions of the kidneys are affected?
Calculi in ureter
What is the pathogenesis of chronic reflux-associated pyelonephritis?
Superimposition of a UTI on congenital vesicoureteral reflux
Can chronic reflux-associated pyelonephritis affect one or both kidneys?
It can be both unilateral or bilateral (scarring and atrophy)
What can chronic reflux-associated pyelonephritis lead to?
Chronic renal insufficiency
What are the gross features of CP?
Scarring involving the pelvis or calyces, or both
What does scarring involving the pelvis/calyces lead to?
Papillary blunting
Marked calyceal deformities
What are the gross features of CP in bilateral involvement?
Kidneys are not equally contracted with uneven scarring
What are the microscopical features of CP?
Uneven interstitial fibrosis and inflammatory infiltrates of lymphocytes and PLASMA CELLS
Tubules are either contracted or dilated and lined atrophic epithelium and contain colloid casts
Glomeruli are usually normal except late when glomerulosclerosis occurs
What is drug-induced interstitial nephritis?
An important cause of renal injury
What can drug-induced interstitial nephritis lead to?
Acute drug-induced tubulointerstitial nephritis (TIN)
What causes drug-induced interstitial nephritis?
Occurs as a result of adverse reaction to many drugs (2 to 40days after exposure)
What are the examples of drugs that can lead to drug-induced interstitial nephritis?
Penicillin
Diuretics
NSAIDs
Other drugs (Phenindione, cimetidine)
What is the pathogenesis of drug-induced interstitial nephritis?
Both type I and type IV HSR
Analgesic nephropathy
What is type I HSR?
IgE mediated
What is type IV HSR?
T-cell mediated
What is the pathogenesis behind type I and IV HSR that lead to drug-induced interstitial nephritis?
- Drug acts as a hapten
- Bind to tubular component (cytoplasmic or extracellular component) during secretion by tubules
- Becomes immunogenic
- Results in tubulointerstitial injury by IgE and cell mediated reactions
What is the pathogenicity behind analgesic neuropathy?
- Phenacetin and aspirin inhibit PG production
- inhibit its vasodilatory effects
- Predisposes interstitial nephritis associated with papillary necrosis
What does Phenacetin do?
Injures cells by oxidative damage
What is drug-induced interstitial nephritis microscopically characterized by?
Interstitial inflammation (lymphocytes and macrophages –> common, eosinophils and neutrophils –> in large numbers)
Glumeruli are normal
In which cause of drug-induced interstitial nephritis are glomeruli not normal?
NSAIDs
What is analgesic nephropathy characterized by? (microscopically)
Coagulative necrosis
How is acute kidney injury defined clinically?
Acute rise in serum creatinine
What are the classifications of AKI?
Prerenal
Intrarenal
Postrenal
What causes pre-renal AKI?
Reduced blood flow to the kidneys
What causes intrarenal AKI?
Injury to the renal parenchyma
What causes post-renal AKI?
Urinary tract obstruction
What are the further categorizations of intra-renal AKI?
Which portion of the kidney is mainly injured:
1. Glomerulus
2. Vessels
3. Tubules
4. Interstitium
What is the most common cause of intra-renal AKI?
Ischemic acute tubular injury
What is the morphological change to ATI?
Damaged tubular epithelial cells
What are the clinical characteristics of ATI?
Acute decline of renal function, with granular casts and tubular cells observed in urine
Reduced GFR –> oliguria with concurrent elevation of serum creatinine followed by electrolyte imbalances and uremia
What are some of the causes of ATI?
Severe glomerular disease
Acute tubular injury caused by diffuse renal vascular diseases
Acute-drug-induced allergic interstitial nephritis
What are examples of diffuse renal vascular diseases?
Microscopic polyangiitis and thrombotic microangiopathies
What are the two forms of ATI?
Toxic
Ischemic
What causes toxic ATI?
Poisons, organic solvents and drugs
What causes ischemic ATI?
Generalized or localized reduction in blood flow
What is the morphology of ischemic ATI?
Lesions in the straight portions of the proximal tubule and the ascending thick limbs
Tubular injuries
What are examples of tubular injuries seen in ischemic ATI? (6)
- Attenuation of proximal tubular brush borders
- Blebbing and sloughing of brush borders
- Vacuolization of cells
- Detachment of tubular cells from their underlying basement membranes with sloughing of cells into the urine
- Presence of proteinaceous casts
- Casts also contain myoglobin
What are examples of proteinaceous casts present in ischemic ATI?
Tamm-Horsfall protein
Hemoglobin
What is the morphology of the interstitium in ATI?
Generalised edema
Mild inflammatory infiltrate (polymorphonuclear leukocytes, lymphocytes and plasma cells)
What is the morphology of toxic ATI?
Similar to ischemic but:
Overt necrosis is most prominent in the proximal tubule
The tubular basement membranes are generally spared
Epithelial regeneration (if the patient survives for a week)
What are the clinical features of ATI?
Rapidly rising serum creatinine, usually decreased urine output
Electrolyte abnormalities, acidosis, signs and symptoms of uremia and fluid overload
What might urinalysis do in the case of ATI?
Help differentiate between the three major intrinsic renal diseases that cause acute renal failure
What are the urine analysis findings of ATI?
Dirty brown casts (tubular cell casts) and epithelial cells
What are the urine analysis findings in acute glomerulonephritis?
Red blood cell casts and proteinuria
What are the urine analysis findings in acute tubulointerstitial nephritis?
White blood cells and pyuria
How does decreased urine output lead to decreased GFR? (ATI Pathogenesis)
- Decreased urine output
- Fluid from damaged tubules may leak into the interstitium (back-leak)
- Increased interstitial pressure
- Decreased tubular fluid flow
- Oliguria and collapse of tubules
- Decreased GFR
How does tubular injury lead to decreased GFR (ATI Pathogenesis)?
- Injury to the epithelial cells
- Detachment of the damaged cells from the basement membrane –> shedding into the urine
- Debris build-up
- Obstruction by casts –> block the outflow of urine
- Increase in intratubular pressure
6 Decrease in GFR
How does interstitial inflammation cause decrease in GFR (ATI Pathogenesis)?
- Interstitial inflammation
- Ischemic tubular cells express chemokines, cytokines, and adhesion molecules
- Recruit leukocytes and cause precipitate in tissue injury
- Decrease in GFR
What is the pathway that ischemic ATI follows?
Ischemia
Vasoconstriction
Tubular Injury
Tubular Backleak OR Slaughed cells OR Interstitial Inflammation
Decreased urine output OR Obstruction OR Decreased GFR
How does ischemia cause a decrease in GFR? (ATI Pathogenesis)
- Ischemia causes numerous structural alterations in the epithelial cells
- Loss of cell polarity leads to the redistribution of membrane proteins
- Increased sodium reabsorption by proximal tubules and hence reduced sodium chloride in distal tubules
- Decreased sodium chloride in distal tubules –> renin production activation –> afferent arteriolar vasoconstriction
- Decreased GFR
