Renal - Acute kidney injury (Pathoma)

Definition
  • Acute, severe dec renal fn (50% of baseline, days)
    • cf  chronic - slow, persistent decrease GFR
      • < 60 ml/min/1.73m2 
      • for 3 months
      • and/or persistent albuminuria
        • End stage - GFR <5% 
  • Azotaemia - inc nitrogenous waste in blood (urea [BUN blood urea nitrogen], creatnine [Cr])
  • Pre-, intra- and post-renal azotaemia
  • Pre: dec blood in
  • Intra: problems inside kidney
  • Post: block urine outflow
  • BUN:Cr  and Urea:Cr helps distinguish
    • Prerenal:
      • B >20:1
      • U > 100:1
      • inc BUN reabs (as concentrating urine) so inc in serum cf Cr
      • eg dehydrn, HF (also get frac excrete Na<1%)
    • Intrarenal:
      • B <10:1
      • U < 40:1
      • kidney damage so can't reabs as much BUN
      • eg Membranous Nephropathy, SLE (nephritic syndrome, haematuria, RBC casts)
    • Normal/Postrenal:
      • BUN:Cr - 10-20:1
      • Urea:Cr 40-100:1
      • eg BPH
Pre-renal
  • Common cause of AKI
  • Dec blood so dec GFR
  • Azotaemia
  • Oligouria
  • Reabsorption of fluid and blood urea increase
    • Serum BUN : Cr > 15 at least (20 classically)
    • (normal ratio = 15)
  • Activates renin-angiotensin axis
    • Kidney thinks hypovolaemic
  • Absorb more Na, H2O and BUN
    • Cr never reabsorbed
    • So get more BUN cf Cr
  • Tubular fn intact (not damaged)
    • FENa < 1% - fractional excretion sodium - can still absorb Na, working fine
    • Urine osmolality > 500 - able to conc urine
  • Causes
    • Generalised hypoperfusion - hypoTN, dec CO etc
    • Renal hypoperfusion - thrombi, atherosclerosis, dissection etc
    • Loss of autoregulation - ACEi (dec renal blood flow), NSAIDs
    • Hepatorenal syndrome
      • Also bile cast nephropathy - toxic to PCT
Post-renal
  • Back pressure due to obstructed outflow
  • Decrease GFR
    • Lose pressure gradient
  • Azotaemia
  • Oliguria
  • Early stages
    • Inc tubular pressures - BUN pushed back into blood/flow slower so more chance to reabs
    • Serum BUN : Cr > 15
    • Tubules still ok at this point
      • FENa < 1%
      • Urine osm > 500
  • Long standing
    • Tubular damage
      • Dec BUN reabs 
        • Serum BUN:Cr < 15
      • Dec Na reabs
        • FENa > 2%
      • Can't conc urine
        • Urine osm < 500
INTRA-RENAL

Acute Tubular Necrosis
  • Injury + necrosis of tubular epithelial cells
    • Due to direct toxicity
  • Most common AKI cause
  • Necrotic cells
    • Slough of and bundle
    • Plug tubules + obstruct = back pressure
    • Dec GFR
    • Show as granular brown casts in pee
      • Look granular as individual dead epithelial cells stuck together
    • On microscopy
      • Lose nuclei (necrosis)
      • Detachment of cells from membrane - sloughing
  • Cells dead so Serum BUN : Cr < 15
  • Dec Na reabs - FENa > 2%
  • Can't conc pee - osm < 500
  • Aetiology
    • Ischaemia - patchy, PCT + TAL
      • Often preceded by pre-renal azotaemia
      • Dec blood supply causes ischaemia
        • Multiple causes
        • Renal artery stenosis or thrombosis
        • Emboli
        • Shock
        • NSAIDs - inhibit COX so muck up autoreg (prostaglandins made to relax afferent arteriole) - NB also causes TIN[+/-nephrotic syndrome]; analgesic nephropathy [a form of papillary necrosis--cumulative---although not just NSAIDs--see later]; long term use at "safe" levels can cause subclinical dysfn which is mostly reversed on ceasing drug.
      • Tubules need shit loads of ATP and waste removeal
      • Proximal tubule and medullary segment of thin asc limb most susceptably



    • Nephrotoxic - diffuse; PCT (+~TAL)
      • Toxins
        • Endogenous
          1. Myoglobinuria - crush injuries etc
          2. Urate - tumour lysis syndrome (e.g. Chemo for ALL - rapid breakdown of proteins, lots of uric acid made - to prevent: allopurinol, hydration) etc
          3. Hb
          4. Ig light chains
          5. Phosphate crystals
        •  Exogenous
          • Aminoglycosides (gentamycin)
          • Vancomycin (glycopeptide)
          • Cyclosporin
          • Radiocontrast
          • Heavy metals - Pb...
          • Ethylene glycol - blue and sweet! kiddies drink! BUT ANTIFREEZE! May get oxalate crystals
          • The tubular vacuolisation and tubular dilation here is a result of the toxic effect of ethylene glycol poisoning. ATN resulting from toxins usually has diffuse tubular involvement, whereas ATN resulting from ischemia (as in profound hypotension from cardiac failure) has patchy tubular involvement.

      • Proximal tubule most susceptible
  • Features
    • Oligouria
    • Brown granular casts
    • Serum BUN and Creatnine
    • Hyperkalaemia - dec renal excretion
    • Metabolic acidosis - can't swap acid for K+
      • inc anion gap
    • Inflammation - due to inc adhesion molecules on cells
  • Reversible
    • Supportive dialysis often needed
    • But electrolyte imbalances due to ATN can be fatal
    • Oligouria may persist
      • 2-3 weeks
      • Tubular cells are stable cells
        • May re-enter cell cycle
        • But currently quiescent
        • So takes time to reenter and regenerate

Acute Interstitial Nephritis or Tubulo-Interstitial [TIN]
  • Interstitial ⇒ connective tissue + tubules in kidney
  • -itis ⇒ inflammatory infiltrate between tubules
  • Causes Intrarenal AKI
  • Type I (IgE, eosinophilic) or Type IV (delayed, cell mediated, granulomatous, +ve skin test) hypersensitivity
  • Mainly drug induced - fortnight after taking
    • NSAIDs
    • Abx
      • Rifampin
      • Penicillins - e.g. methicillin
      • Cephalosporins
    • Diuretics - e.g. thiazides, loop
    • Cimetidine - H2 antag
    • Allopurinol
    • Sulfonamides
  • Presents
    • days to weeks post starting drug
    • Oliguria
    • Fever
    • Rash
    • Eosinophils in urine
    • Histo
      •  Oedema
      • Macrophages
      • Lymphocytes
      • Eosinophils if type I
      • Possible neutrophils
      • Poss most inflm in medulla - contrating zone!
      • Non-necrotising granuomas - mrthiclin, thiazides
      • NSAIDs: also get glomerular involvement as causes nephrotic, minimal change also
      • Analgesic Nephropathy (phenacetin - banned) - papillary necrosis
    • Resolves on cessation (hypersens rxn)
    • May progress to Renal  Necrosis

Renal Papillary Necrosis
  • Papillae die
  • Gross heamaturia
  • Flank pain
  • Kids and adults
  • Causes
    • Chronic analgesia abuse - long term aspirin, Phenacetin (old, banned paracetamol pro drug), paracetamol
    • Diabetes mellitus
    • Sickle cell disease or trait
    • Severe acute pyelonephritis
    • Progression from acute interstitial nephritis
    • Ascending infection
    • POSTCARDS = causes:
      • pyelonephritis
      • obstruction of the urogenital tract
      • sickle cell disease
      • tuberculosis
      • chronic liver disease
      • analgesia/alcohol abuse
      • renal transplant rejection
      • diabetes mellitus
      • systemic vasculitis

  • The pale white areas involving some or all of many renal papillae are areas of papillary necrosis. This is an uncommon but severe complication of acute pyelonephritis (an infective cause), particularly in persons with diabetes mellitus. Papillary necrosis may also accompany analgesic nephropathy.

NSAID nephropathy
  • AKI
    • dec PG so less vasodil - ischaemia
  • Acute hypersen intersitial nephritis (above)
  • " " " + minimal change disease 
    • Renal failure + nephrotic syndrome
    • interstital, glomerular and podocyte injury
  • Membranous nepthropathy
    • Nephrotic

Other tubulointerstitial diseases
  • Urate Nephropathy
    • Acute
      • Crystals in collecting ducts
      • Obstruct
      • Tumour lysis sundrome
      • Inc risk if acidic pH
    • Chronic
      • Gouty
      • Monosodium urate
      • Distal tubule, colelcting ducts, interstitium
      • Granuloma - tophus
      • Pb?
    • Nephrolithiasis
  • Hypercalcaemia: nepthocalcinosis
    • Hyperthyroid, multiple myeloma, xs VitD, mets, milk-alkali syndrome
    • Calcium stones
    • Can't conc
    • ATN with acidosis, salt wasting
  • Acute phosphate nephropathy
    • Calcium phosphate


Dialysis may be required
  • Fistulae complications
    • NO SHITS

    • Neuropathy (ischaemic)
    • Oedema

    • Stenosis
    • Heart failure
    • Infection
    • Thrombosis
    • Steal syndrome





Acurte renal failure 1_2.pdf

Acurte renal failure 3_4.pdf
Acurte renal failure 5_6.pdf

Robbins Basic Pathology, Robbins Pathologic Basis of Disease, Robbins Review of Pathology (MCQs - very path-y), Robbins Flash Cards, Baby Robbins, Robbins Atlas - some exact same images come up in the exam, 100 Cases in ClinicalPathology - possibly the best Qbank for the practical