9/21- Tubular Disorders Flashcards Preview

MS2 Renal > 9/21- Tubular Disorders > Flashcards

Flashcards in 9/21- Tubular Disorders Deck (37)
1

What is the kidney interstitial space?

Space between tubules and glomeruli containing vasculature and connective tissue cells

- May be damaged by primary disease or secondary process

- Interstitial space, tubule, and glomerulus function as a unit; damage to one component will affect others

2

What is seen here? 

Normal kidney anatomy

- Glomerulus and Bowman's capsule

- Tubules- (columnar epithelium)

3

What is seen here? 

Acute changes: edema and cellular infiltrates

- Many "black dots" and "red jello"

- Top arrow = black dot with surrounding red = eosinophilia

- Can see space between tubules; edema and swelling (multicellular infiltrates between tubules)

4

What is seen here? 

Chronic renal changes:

- Tubule dilation and degeneration

- Fibrosis

- Interstitial space (space between tubules) but without inflammatoryinfiltrate

5

What is seen here?

Chronic renal changes:

- Glomerulosclerosis

- Vascular sclerosis

6

What are urinary findings and disease examples in damage to:

- Tubule

- Interstitial space

- Urinary obstruction

- Glomerular disease

- Renal cystic disease

- Metabolic disease

Tubule

- Ex: ATN (acute tubular necrosis)

- Urine: granular casts

Interstitial space

- Ex: pyelonephritis

- Urine: WBC (neutrophils), bacteria, culture

Also IS space:

- Ex: Allergic IN

- Urine: WBC (eosinophils), (-) culture

Urinary obstruction

- Ex: BPH

- Urine: Benign urine

Glomerular disease

- Ex: Membranous GN

- Urine: Proteinuria, hematuria

Renal cystic disease

- Ex: Polycystic kidney disease

- Urine: Hematuria

Metabolic disease

- Ex: Cystinuria

- Urine: Urinary crystals

7

List of etiologies of interstitial diseases (don't memorize)?

- Infections: bacterial, fungal, viral, mycobacterial

- Drugs: NSAIDS, herbals, cisplatinum, lithium, others

- Hematopoietic Diseases: sickle cell, myeloma and lymphoproliferative disorders

- Obstruction: VUR, mechanical

- Heavy Metals: lead, cadmium, etc

- Hereditary Diseases: PCKD, medullary cystic dis., hereditary nephritis, medullary sponge kidney, juvenile nephronophthisis, etc

- Metabolic Disorders: diabetes mellitus, hyperuricemia, cystinosis, K+ depletion, oxaluria, hypercalcemia

- Immunologic Diseases: SLE, Transplanted kidney, cryoglobulinemia, Sjögrens, Goodpasture

8

What are methods of bacterial kidney infection (spread)?

- Systemic seeding by staph and strep

- Ascending infections: gram neg organisms, enterococcus (may present as cystitis)

9

Common infectious agents that may cause kidney infection/tubulo-interstitial inflammation?

Bacteria

- Staph, strep

- Gram (-) organisms, enterococcus

Viral: CMV, HIV, BK (polyoma), EBV, Hantavirus, herpes

Fungal: typ candida

Mycoplasma

Other: malaria, leptospira

10

What is seen here?

Pyelonephritis on CT scan

- Striated nephrogram- poorly perfused area 

11

What can cause interstitial inflammation from a urinary reflux/obstruction standpoint?

- Clinical presentation

- Treatment

Vesico-urethral reflux nephropathy

- Caused by combo of VUR and infection, beginning in childhood

Clinically:

- Recurrent UTIs in childhood

- Slowly progressive loss of kidney function

Treatment

- Treat UTIs

- Correct severe VUR in children

- No benefit of surgery in adults

12

What is involved in acute drug induced interstitial nephritis and heavy metal toxicity as etiologies for interstitial inflammation? (Basic principles)

- The drugs causing interstitial inflammation are an unrelated group of agents that aren't dose related and only occur in small number of exposed

- Overall, it's a hypersensitivity reaction; recurs (severe) upon re-exposure

- May involve systemic manifestations

13

What drugs can cause interstitial inflammation?

Antibiotics

- Penicillins, methicillin, ampicillin

- Cephalosproins, floroquinolones (cipro)

- Rifampin

Sulfonamides

NSAIDs (analgesics)

Miscellaneous:

- Anticoags (Phenindione)

- Anticonvulsants (Phenytoin)

- Diuretics (Thiazides, Furosemide)

- Others: Cimetidine, Allopurinol, Cyclosporine, Omeprazole

14

Acute physical findings of tubule and interstitial disease?

- Fever, 50-75%

- Rash, 25-40%

- Eosinophilia, 40-60%

- Flank pain, 25-40%

- Hypertension, 10-20%

15

What is the association between Aristolochic acid and nephropathy?

Aristolochic acid nephropathy (AAN) aka Chinese herbal nephropathy

- Extensive paucicellular interstitial fibrosis and tubular atrophy typically found in end-stage CHN

16

Describe NSAID (analgesic) nephropathy:

- Clinical Presentation

- Onset

- Urinalysis

- Resolution

- Permanent damage (prevalence)

- Systemic manifestations

- Clinical Presentation: AKD +/- Nephrotic Syndrome

- Onset: 2 wks - 18 mo

- Urinalysis: microhematuria, pyuria

- Resolution: 1 mo - more than 1 yr

- Permanent damage (prevalence): perhaps > 15%

- Systemic manifestations: eosinophilia, fever, rash

17

Clinical Features of NSAID nephropathy?

- Gender

- Age

- Symptoms

- Gender: female > male (60-85%)

- Age > 30 yrs

- Personality disorder (Major 35% Minor 40% Introvert, dependent, anxiety, emotional disorder, neurotic, familial instability)

- Addictive syndrome (Smoking, alcohol, laxatives, sedatives, psychotropics)

- Cause of analgesic dependency (Headache 40-60%, mood 6-30%, musculoskeletal pain 20-30%)

18

Pathogenesis of NSAID nephropathy?

APC tabs or powders

- Aspirin blocks synthesis of prostaglandin (a vasodilator)

- Phenacetin (Acetaminophen)* lowers glutathione, which is needed to block intracellular oxidative stress

- Caffeine increases adenosine, a vasoconstrictor (works in headaches by decreasing CNS edema)

Results in papillary ischemia

*Can take Tylenol rather than Phenacitin/Acetaminophin

19

What is seen here? 

NSAID nephropathy

- Dying papilla

- Dead tissue coming out in urine

20

How can creatinine levels be normal early on?

- Cortical nephron spared

- Decreased GFR, but early creatinine is normal ?

21

Treatment for NSAID Nephropathy?

- Discontinue analgesics

- Control blood pressure (ACEIs)

- Treat urinary infections

- Expand vascular volume

- Psychological support and guidance

- Monitor for uroepithilial neoplasms (5-10% of phenacetin users)

22

What heavy metals can cause nephrotoxicity?

Chronic TIN

- Lead

- Bismuth, Cadmium, Chromium, Copper, Iron, Mercury, Platinum, Silicon, Uranium

Acute TIN

- Bismuth

- Mercury

- Uranium 

- Arsenic, Cadmium, Chromium, Copper, Gold, Iron, Lead, Silver

23

ATN and cortical necrosis can cause tubulo-interstitial inflammation. What does ATN involve?

Acute tubular necrosis involves multiple renal insults

- Preexisting renal damage

- Prerenal state: volume depletion, sepsis, heart failure

- Nephrotoxin exposure or kidney ischemia

24

What is the pathogenesis of ATN?

- Cell death due to toxin or ischemia

- With reperfusion, damaged cells undergo apoptosis

- Damaged cells sloughed off and new cells take their place

- Combination of vasoconstriction (pre renal state), ischemia, and toxin

- Vacuolization of tubules, loss of transport polarity

- Sloughing of cells, cast formation

- Recovery typically 1-3 weeks

- Clinical objective, keep patient alive till kidneys recover

25

What is seen here? 

ATN in kidney biopsy

- Cells sloughing off in collecting tubule and forming cast

26

What nephrotoxins can cause acute tubular necrosis?

- IV iodinated radiographic contrast

- Heme pigments (myoglobin and hemoglobin)

- Certain antibiotics (aminoglycosides)

- Heavy metals (cis-platinum)

- Carbon tetrachloride and solvents

27

What can cause cortical necrosis?

Ischemia of cortex

- Microvascular thrombosis, glomerular and tubule damage

- Medulla may survive

- Damage is patchy, some renal function may remain

Obstetrical disorders, DIC, HUS (E. coli infxn)

Anuria or oliguria is common

28

What is seen here? 

Cortical necrosis

29

What conditions can cause urinary crystals?

- Metabolic disease

- Medications

- Chemicals

- Other

Metabolic disease

- Cysteine

- Hyperuricemia

- Hypercalcemia

Medications

- Indinavir

- Foscarnet

- Sulfa drugs

Chemicals

- Antifreeze (oxalic acid crystals)

Triple phosphate crystals and staghorn calculi (chronic kidney infection with urea splitting agents)

30

What can cause Cysteinosis? Cysteinuria?

Cysteinosis- autosomal recessive

- Cysteine accumulates in cells

- Proximal nephron damaged, unable to reabsorb filtered glucose, bicarb, AAs (Fanconi syndrome)

Cystinuria- autosomal recessive

- Filtered cysteine not reabsorbed by proximal nephron

- High urinary levels precipitate in pH neutral or acid urine, causing cysteine kidney stones

31

What crystals are these? 

32

What is Myeloma Cast Nephropathy?

- Plasma cell clone produces defective antibody parts, excessive kappa or lambda chains

- Direct proximal tubule toxicity, cast formation in collecting duct

- Associated bone lesions, proteinuria (kappa and lambda proteins not detected by urinary dip stick)

- Anemia

- Small anion gap (kappa and lambda are positively charged proteins)

33

What is seen here? 

Myeloma Cast Nephropathy

- Due to toxicity of filtered light chain (kappa, lambda) proteins; Bence Jones

- Directly toxic to proximal tubular cells

- Precipitate int he distal and collecting tubules

34

What is papillary necrosis?

- Necrosis of papilla: long loops of Henle, vasa recta, collecting duct

- Flank pain, tissue in urine

- Sickle cell, analgesic abuse, pyelonephritis...

- Not usually oliguric or anuric (humans have multiple papilla) 

35

What happens to the nephrone/tubule in renal papillary necrosis? GFR?

- Loss of justamedullary nephrons

- Cortical nephrons preserved

- Tubular dysfunction but GFR maintained until disease advanced

36

What is seen here? 

Left: Normal

Right: Sickle cell renal disease

37

Summary:

- Tubule and interstitial diseases share a common inflammatory pathogenesis

- Interstitial renal disease results in characteristic tubule defects

- Multitudes of common substances can cause TIN-be suspicious and pay attention to prescribed and over-the-counter medications

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