Tubular and Interstitial Diseases Flashcards
What two major processes lead to clinical manifestations in acute kidney injury?
- Ischemic or toxic tubular injury
- Inflammation of the tubules and interstitium
What is ischemic ATI due to?
- Due to decreased or interrupted blood flow
What is nephrotoxic ATI due to?
- May be caused by endogenous agents
What are present and considered pathognomonic of ATI? What is the association?
- Abundance of the “extreme” coarsely granular casts
- Associated with a greater likelihood of dialysis requiring acute kidney injury
What is responsible for the color of the casts seen in ATI?
- Mitochondrial pigments or lipofuscin
When is the initiation phase of AKI?
- Lasts 36 hours
What is seen in the initiation phase of AKI?
- Dominated by the inciting medical, surgical, or obstetric event
- Only renal involvement sign is a slight decline in urine output with a rise in BUN
What is the maintenance phase characterized by?
- Sustained decreases in urine output to between 40 and 400 mL/day
- Salt and water overload
- Rising BUN concentrations
- Hyperkalemia
- Metabolic acidosis
- Other manifestations of uremia
What is seen in the recovery phase of AKI?
- Steady increase in urine volume that may reach up to 3L /day
- Tubules are still damaged, so large amounts of water, sodium, and potassium are lost in the flood of urine
What is a big clinical problem in the recovery phase of AKI?
- Hypokalemia due to potassium loss
How are tubulointerstitial disorders distinguished from glomerular diseases?
- Absence of nephritic or nephrotic syndrome
- Presence of defects in tubular function such as impaired ability to concentrate urine, evidenced clinically by:
1. Polyuria or nocturia
2. Salt wasting
3. Diminished ability to excrete acids
4. Isolated defects in tubular reabsorption or secretion
What is acute pyelonephritis?
- Generally caused by bacterial infection and is associated with UTI
- Suppurative inflammatory process involving the kidney that is the result of bacterial and sometimes viral infection
What is chronic pyelonephritis?
- More complex disorder
- Bacterial infection plays a dominant role, but other factors predispose to repeat episodes of acute pyelonephritis
What are some associations with acute pyelonephritis?
- Urinary tract obstruction
- Instrumentation
- VUR
- Pregnancy
- Gender and age
- Pre Existing renal lesions
- Diabetes
- Immunosuppression and immunodeficiency
How does acute pyelonephritis present?
- CVA tenderness
- Systemic features (fever, elevated WBC)
- Dysuria, frequency, urgency
How can uncomplicated E. coli cystitis be treated?
- With a single dose of antibiotics or a 3 day course of TMP/SMZ or nitrofurantion
What is a viral pathogen that causes pyelonephritis in kidney allografts?
- Polyomavirus
What is polyomavirus infection characterized by?
- Nuclear enlargement and intranuclear inclusions visible by light microscopy in tubular epithelial cells
What are some complications of pyelonephritis?
- Papillary necrosis
- Pyonephrosis
- Perinephric abscess
Who is most likely affected with papillary necrosis?
- Diabetics
- Sickle cell disease
- In those with urinary tract obstruction
What is papillary necrosis?
- One or all of the pyramids of the affected kidney may be involved
- On cut section, tips or distal two thirds of the pyramids have areas of gray-white to yellow necrosis
What is seen on microscopic examination in papillary necrosis?
- The necrotic tissue shows characteristic ischemic coagulative necrosis, with preservation of outlines of tubules
What is pyonpehrosis?
- Is seen when there is total or almost complete obstruction, particularly when it is high in the urinary tract
- Suppurative exudate is unable to drain and fills the renal pelvis, calyces, and ureter with pus
What is a perinephric abscess?
- An extension of suppurative inflammation through the renal capsule into the perinephric tissue
What is a staghorn calculus?
- Dilated calyces
- Cystic cavities
- Yellow tissue
What is seen on histology in a staghorn calculus?
- Fibrosis and chronic granulomatous inflammatory infiltrate with lipid laden foamy macrophages and necrotic debris
What types of agars are used for pus and urine samples?
- Blood agar
- MacConkey agar
What can grow on blood agar?
- Proteus grows in successive waves to form a thin filmy layer of concentric circles
What is the treatment for an uncomplicated UTI due to P. mirabilis?
- 3 day course of TMP/SMZ or an oral fluoroquinolone
What is the treatment for a complicated UTI due to P. mirabilis?
- Outpatient setting with oral antibiotics for 10 to 21 days as long as they receive adequate follow up
What is the second most common cause of AKI?
- Drug- and toxin-induced tubulointerstitial nephritis
What are some causes of drug- and toxin-induced tubulointerstitial nephritis?
- Sulfonamides
- Synthetic penicillins
- Other synthetic antibiotics
- Diuretics
- NSAIDs
How can toxins and drugs injure kidneys?
- Trigger an interstitial immunologic reaction, exemplified by the acute hypersensitivity nephritis induced by drugs
- Cause ATI
- Cause subclinical but cumulative injury to tubules that takes years to result in chronic kidney disease
What is drug induced acute interstitial nephritis characterized by?
- Fever
- Eosinophilia
- Rash
- Renal abnormalities (hematuria, mild proteinuria, and leukocyturia)
- Rising serum creatinine or AKI with oliguria
What are the three types of nephropathy with hyperuricemia?
- Acute uric acid nephropathy
- Chronic urate nephropathy
- Nephrolithiasis
What does tumor lysis syndrome result from?
- Release of intracellular electrolytes and nucleic acids from malignant cells that were lysed by anticancer therapies
What is tumor lysis syndrome characterized by?
- Increases in serum levels of uric acid, potassium, and phosphorus
- Accompanied by hypocalcemia
What can disorders associated with hypercalcemia lead to?
- Kidney stones
- Chronic tubulointerstitial disease
- Renal insufficiency
What distinctive genetic mutations are seen in autosomal dominant tubulointerstitial kidney disease (ADTKD)?
- MUC1 encodes mucin-1
- UMOD encodes uromodulin
- REN encodes preprorenin
- HNF1B encodes hepatocyte nuclear factor 1B
What are some contributing factors to kidney damage in multiple myeloma?
- Bence Jones proteinuria and nephropathy
- Amyloidosis of AL type
- Light chain deposition disease
- Hypercalcemia and hyperuricemia
What does uromodulin do?
- Tamm-Horsfall protein
- Guardian of urinary and systemic homeostasis
What do mutations in THP (uromodulin) cause?
- Increased risks of UTI, kidney stone, hypertension, hyperuricemia, and acute and chronic kidney diseases
What is hepatorenal syndrome?
- Form of renal failure occurring in individuals with liver failure in whom there is no intrinsic morphologic or functional cause for kidney dysfunction
What marks the onset of hepatorenal syndrome?
- Drop in urine output and increasing levels of urea and creatinine in the blood
What is seen in patients with hepatorenal syndrome?
- Portal hypertension due to cirrhosis
- Severe alcoholic hepatitis
- Metastatic tumors
