Acute Kidney Injury and Tubulointersticial Disease Flashcards
Guidelines for Acute Kideny Injury (AKI) (3)
- Incr in serum creatinine of 0.3mg/dL within 48HR.
- Incr serum creatinine of 1.5x the baseline level within 1 week
- Urine production of <0.5mL/kg/HR.per 6HR (oliguria)
Normal creatinine values males and females
-Males: 0.74-1.3 mg/dL
-Females: 0.5-1 mg/dL
Graph of your AKI
Prenal AKI mayor causes
-NSAIDS (chronic pain),Burns,Cardiogenic shock, Hemorrages,Diarrhea
-Hypo-albuminuria (Hepato-Renal syndrome)
-HF (Cardio-Renal syndrome)
-All relate Hypo-perfusion.
Pathophysiology of Pre-renal AKI..
-Hypoperfusion–>Incr. RAAS system–>Hypertension+reabsp of H2O and Na+(less Na and H2O in urine)–>less H2O in lumen your BUN INCR.
-All this is possible because** tubules are NOT damaged**.
What do you expect in Pre-renal AKI
1.Urine osmolarity: concentrated or Diluted
2.GFR: incre or decr
3.Urine Na+ :incr or decr
4.FE%Na+ :incr or decr
5.serum BUN/Creatinine: incr or decr
1.Increase (>500mOsm/Kg)
2.Decr GFR
3.Decr. (<20)
4.Decr (1%)
5.Incr (20:1 ratio)
Why do you NOT see a AKI when only one kidney is affected?
-The other kidney will be able to withstand the load.
-Dosent permit increase in creatinine nor oliguria.
Post-Renal AKI associated with…(2)
-Pathophysiology
-Obstructions BELOW bladder–>in order to affect both kidneys.
-BPH,Post urethral valve (congenital), advanced stage cervical cancer.
-Backflow–> 1.Damaged Tubules:absp is affected (values as intrarenal)
2.Non-damgaed tubules:absp is FUNCTIONAL (values as Pre-renal)
Intra-Renal AKI sub-divisions(3) ans associations
-Vascular–>Vasculitis
-Glomerular-->Glomerulonephritis (RPGN)
-Tubular–>1.Acute Tubular Necrosis-->a)Ischemia and b)Toxins (myoglobin,aminoglycosides,contrast agents, metals,cisplatin)
2.Tubulointerstitial Nephritis (Tubular Acidosis, Pyelonephritis,Drugs)
What are the Toxins associated with Acute Tubular Necrosis in Intra-renal AKI?
-Myoglobin,Contrast agents, aminoglycosides,cisplatin,metals,MTX,anti-freeze
Pathophysiology of Intra-Renal AKI…
-NO Functional Tubules–>cannot regulate
What do you see in INTRA-RENAL AKI
1.Urine osmolarity: concentrated or Diluted
2.GFR: incre or decr
3.Urine Na+ :incr or decr
4.FE%Na+ :incr or decr
5.serum BUN/Creatinine: incr or decr
1.Diluted (<350)
2.-Decr GFR (specially in Acute Tubular Necrosis–>sloughing of cells casuing obstr–>incr glomerular hydrostatic pressure).
3.(>40)
4.(>2%)
5.(<15:1)
How so we differentiate between** Damaged Post renal AKI vs Acute Tubular Necrosis Intra renal AKI**?
-POST-RENAL Damaged:urianalysis (nothings)
-Acute Tubular Necrosis: urianalysis you see renal tubular cell cast (muddy brown app)
Acute Glomerulonephritis (Intra renal) present similar to…
WHY?
-Pre renal AKI
-Its not affecting Tubules,only the glomerulus
How to diffbetween Pre-renal AKI vs. Acute Glomerulonephritis (Intra-renal)?
-Pre-renal:urianalysis normal or Hyaline cast
-Acute Glomerulonephritis:RBC cast or hematuria
Can your Pre-renal and Post-renal AKI progress to Intra-renal AKI?
-YES
-This is why a patient that suffers a severe burn is given IV fluids immediatly do prevent progression to Intrarenal AKI.
Complications of AKI(3)
-Hyperkalemia, metabolic acidosis and hyperurecemia–>serotitis.
Fill the table:
What are the 2 main causes of Acute Tubular Necrosis?
-Ischemia (any hypovolemia states–>cardiogenic shock, hemorrage, burns, sepsis,NSAIDS)–>how it relates to pre-renal injury progressing to intra-renal injury.
-Toxins (myoglobin–>rhabdomyolysis, so -statins may also cause it, cisplatin,MTX, antifreeze, aminoglycosides, metals (Lead), contrast dyes)
Prognosis of Acute Tubular Necrosis
Ischemia–>Poor
Toxins–>Good
Pathophysiology of Acute Tubular Necrosis..
-Ischemia (either toxins or ischemia by hypoperfusion)–>3 changes -Na+/K+ ATPase moves from basolateral to apical surface, -Integrins decr. and -Tight junctions also decr.–>NOT being able to reabsp. Na+, therfore incr lumen sodium promoting H2O to follow** and Epi cells are easier tu slough off–>causing lumen obstruction and **DECR GFR **due to backflow.
-The further decr in volume in blood due to H2O excretion will worsen the necrosis.
Why is Acute TubulaR Necrosis considered a Intrinsic AKI?
-Obstruction it has on renal tubules.
ATN ischemia associated with..
-NSAIDS,cardiogenic shock,Hemmorages,anythings that casues hypoperfusion.
-Same as Pre-renal injury.This is why we sat that pre-renal injuries cause Intrinsic AKI.
ATN toxin type is associated with…
-Aminoglycosides,contrats dyes,cisplation,anti-freeze, myoglobin,uric-acid,Lead poison….
Biopsy and location wise, how do you differentiate ischemia and toxin mediated ATN?
-Ischemia:dscontinous damage/Damages areas high in energy consumption (PCT and Asc Loop of Henle)
-Toxin:continous damage/ Damages first encountered area–>PCT.
What are the stages in ATN and what do you see?
1.Injury:decline urine output
2.Mantainance: INCR BUN/creatinine, oliguria (<400mL/Day),Hyperkalemia–>most comm cause of death due to fatal arrythmias. Last for 3 weeks
3.Recovery: Tubular Re-Epithelization.** HYPOKALEMIA**
Diagnosis and decribe what you see..(3)
-ATN
-Blockage on tubule lumen (WHY?)
-Muddy brown CAST (granular cast)-->necrosis of epi cells,
-Epi cell flattening
Lead posoning presentation?
-Inhb Ferrochelatase–>incr protoporphirin +Microcytic anemia+Basophilic stippling on Blood smear.
Causes of Interstitial nephritis (8)
-Drugs 5P’s (Pee-Diuretics-Thiazide and Furosemide./Pencillin and Chephalosporins /Rimfampin/PPI (Omeprazole)/Pain-free (NSAIDS) and Sulfa drugs)
-Infections:Acute and Chronic Pyelonephritis
-Toxins:Analgesic
-Metabolic:Light chains cast Nephropathy (M.M), Urate Nephropathy, Nephrocalcinosis, **Transplant rejection. **
Diagnosis
Inflamation of Renal interstitium and tubules relating drug use.
-Presentation is malaise,fever rash
-Interstitial Nephritis.
What mechanism of damage does Interstitial nephritis involve?
-Type 1 or 4 Hypersensitivity reaction.
-Drugs will act as a hapten–>triggering of Imm system.
Urianalysis of Interstitial Nephritis relating drugs and what should the history include + presentation?
-Elavated BUN/creatinine, sterile pyuria, EOSINPHILS,WBC cast
-History of drug use. **
-TRIAD:Fever,malaise, rash**–>Hypersensitivity reaction.
Differentiate
Acute vs. Chronic Interstilial Nephritis
-Eosinphils in Acute-Lymphocytes (mononuclear cells) in Chronic.
Complications of Acute Pyelonephritis(2)
Presentation
Where does it affect?
-Perinephric abscess,Renal Papillary Necrosis, Chronic Pyelonephritis
LM:**coagulative necrosis. **
-Fever,malaise,nausea/vomiting,costoverterbral angle tenderness
-Invades interstitium–>spares glomerulus and vessels
Diagnosis
-Acute Puelonephritis (abscess)
Chronic Pyelonephritis gross description?
-How do you describe if you see eosinphilic cast?
-Blunted Calyces and Papilla
-Scarring of same areas.
-Flattening of upper and lower papillae.
Thyrozydation.
Why blunting of specific lower and upper papillae in chronic pyelonephritis?
-They are compound papillae.
2 types of Chronic Pyelonephritis and how to differentiate?
-Obstructive:hydronephrosis, scarring everywhere, thin cortex
-Reflux:scarring in upper and lower papillaes
What is Xantogranulomatous Pyelonephritis?
What microbe is it associated with and what do you see in Biopsy?
-Ass with Chronic pyelonephritis that has nodules that mimmic tumor–>ass with Proteus Mirabilis infections.
-On biopsy you see Foamy macrophages.
What pre-disposing conditions will cause NSAID Nephropathy?
- **Hypovolemia or setting of renal disease. **
- Giving NSAIDS in this situations will cause NSAID Nephropathy.
What drugs cause Analgesic Nephroptahy and what complications (2) they have?
-Acetaminophen (Tylenol)+Apsirin everyday for varoius yr’s.
-Transitional Urinary Tract Cancer + Renal Papillary Necrosis.
Causes of Papillary Necrosis?(4)
-N**SAIDS, Acute Pyelonephritis, Diabetus Mellitus,Sickle cell dis or trait. **
How to differentiate between Diabetic and Analgesic Renal Papillary Necrosis?
-Diabetic:all cells are in similar stage of damage
-Analgesic:cells are at diff stage
Both cause oxidative damage.
What do you see microscopally in Analgesic Nephroptahy?
-Papillary necrosis + Dysmorphic Calcification.
Where does you analgesic concentrate in kideny?
Medulla
Where do you see Fibrinoid Necrosis?
-Some **Vasculitis, Hyper-acute rejection, and Malignant Hypertension. **
Tumor Lysis syndrome presentation
-Blood work?
-Hyperkalemia,Hyperphosphatemia,Hypocalcemia,
Hyperuricemia.
-arrythmias,peaked T waves, seizures, muscle weakness, Tetany, Acute kideny Injury. **
DIAGNOSIS
Patient has Leukemia/Lymphoma ands gets his first chemotherapy treatment and develops muscle weakness, arrythmias and seizures?
-Tumor Lysis Syndrome (High cell turnover)
**Uric Nephropathy is ass with?
Tumor Lysis Syndrome.
How to we prevent Tumor Lysis Syndrome?
-Allopurinol.Agrresive Hydrated,Rasburicase(inhb allantoin formation)
Why Rasburicase is better than Allopurinol for tretament of prevention of Tumor Lysis Syndrome?
-Prevents Xanthine from precipitating.
-Lower uric acid levels faster
What are the 3 test you do for diagnosing a plasma dyscracia disease and why?
-Serum Protein Electrophoresis–> elevated Ig production (M spike)
-24hr. Urianalyses: Light chain Ig that gets filtered.
-Bones marrow biopsy (confirmation):
Multiple Myeloma pathogenesis:
-Plasma Cell Dyscracia–>IgG overproduction.
-CRAB:HyperCalcemia, Renal Acute Injury, Anemia and Bones lytic lesions. **
-urine dipstick:usually shows for albumin.
-Blood smear:”Rolex Formation”
-Biopsy: monoclonal plasma cells–>reasson of anemia.
-24HR urine test: Bence Jones Protein=Ig**
Complications of Multiple Myeloma?
-Primary amyloidosis–>Renal injury (Ligth Chain Nephropathy)
-incr risk of infection.
Renal Tubular Acidosis types and what they ALL have in common?
-Type 1-cannot secrete H+ from alpha intercalted cells
-Type 2 -not able to reabsp HCO-3 due to decf. of Carbonic Anhydrase in PCT.
-Type 4-aldosterone decf. or aldosterone sensative.
-All have Normal Anion Gap Metabolic Acidosis
Type 1 RTA defective Transporters?
-H+ ATPase **
-H+/K+ ATPase also affected (reabsp K+)**
-Both on **alpha intercalated cells. **
What is associated with Type 1 RTA..(4)
-Complications (2)
-Lithium (mayorly excrted by kidney)
-Genetic mutations
-R.A
-SJorgen Syndrome
-Incr risk of Ca++-Phosphate stones and Hypercalciuria–>fracture–>actions to buffer alkaline urine.
-due to urine pH and bone turnover related to buffering.
What drug ?
Mood stabilizer for bipolar disorder; treats acute** manic episodes** and prevents relapse.
Adverse effect
Lithium.
-Diabetus Insipidus** (Amiloride)**
Type 2 RTA pathogenesis..
-PCT cannot reabsp. HCO-3–> metabolic acidosis
-Excess HCO-3 in lumen–>osmotic diuresis–>mild hypovolemia–>RAAS activation->Na+reabsp. and K+ excretion–>Hypokalemia.
-When urine is not acidic–>theres no need to excrete HCO-3–> it will be reabsp.–>Acidic urine
Associated events with Type 2 RTA? (3)
-Everything that excretes HCO-3
-Acetozolamide, Topiramate (Carbonic Anhydraze Inhb.)
-Faucconi syndrome (disorder with PCT reabsp.)..
-Multiple Myeloma (Light Chain Nephropathy)
Why urine pH is acidic in Type 2 RTA?
-Because as you decr H+ in lumen of tubules you reabsp. more HCO-3–>causing a acidic urine.
Diagnosis
glycosuria,aminoaciduria,phosphouria,and uric acid on urine.
-Faucconi syndrome(defective PCT)
Type 4 RTA pathogenesis
Defc in aldosterone or alsodterone sensitivity.
-Non-functional aldosterone–>NO H+ nor K+ excretion–>metabolic acidosis and Hyperkalemia.
-Collecting tubules.
Disorders associated with Type 4 RTA? (4)
-Spironolactone chronic use
-Addison disease
-Diabethic nepgropathy.
-ACHE inhb., ARB,Aloskiren
Location of pathology of each RTA
Type 1
Type 2
Type 4
-ALPHA intercalted cell
-PCT
- collecting tubules (aldosterone recep)
Diagnosis
normal anion Gap metabolic acidosis
**urine pH >5.5 **
**Hypokalemia **
Type 1 RTA
-ATPase mutation,R.A, SJorgen syndrome, Lithium
Diagnosis RTA
Normal Gap Metabolic Acidosis
Hyperkalemia
urine pH<5.5
Type 4 RTA
-pH <5.5 because HCO-3 starts to get reabsp.
-Spironolactone, Addison disease, Diabetic Nephropathy.
Normal Anion Gap Metabolic Acidosis
urine pH <5.5
Hypokalemia
Type 2 RTA
-Hypokalemia due to activation of RAAS by HCO-3 by osmotic diuresis–>mild hypovolemia.
Hyperkalemia RTA. Think off
TYPE 4 RTA
Hypokalemia RTA, what do you see next?
-Type 1 and 2–>you look at pH
-pH>5.5–>Type 1
-ph<5.5–>Type 2
Hyperacute Transplant rejection pathogenesis
-type 2 hypersensitivity, preformed antibodies towards donar graft.
-Within minutes.
-Excessive endothelial injury–>**Thrombosis–>Fibrinoid necrosis due to ischemia
-After transplantation
-Hyper-acute transplant rejection.
Acute Transplant rejection pathogenesis
-Type 4 Hypersensitivity
-Humoral (antibodies) and Cellular response–>CD8+ and CD4+–>they acts against donor MHC.
Type of Transplant Rejection
-Inflamation of Interstitium and tubules–> you see lymphocytes in interstitium–>vasculitis
-Well prevented with immunosupression since it has **cytokine mediated damage. **
-Hyperacute
Chronic Graft Rejection
-Type 2 and 4 Hypersensitivity.
-CD4+ reacting to recipient APC presenting Donor peptides. (MHC)
-Specific for arteriolosclerosis–>occluding vessels for long times–>damage.
-Proliferation of smooth muscle–>paranchymal atrophy **and interstitial fibrosis.
-Thrombosis
-Interstitial inflamation
-Arteriolosclerosis (smooth muscle proliferation)
Nephrocalcinosis
-Presents as Diabetus Insipidus__> NO dysuris, poluris and inability to concentrate urine/;
-Nephrolithiasis
-Tubular defects - poor concentrating
ability (polyuria), salt wasting, and
renal tubular acidosis.
Ass disease with nephrocalcinosis
-PTH tumor, excess vit. D, sarcoidosis, renal osteodystrophy, mil-alki syndrome.
post rena AKI long term gross app(2)
-Dilation pelvis and kidney and tubules atrophy
