Renal 2.77-84 Flashcards
What composes the glomerular barrier?
- Fenestrated capillary endothelium
- Trilaminar glomerular basement membrane
- Foot processes of podocyte cells forming filtration slits
(Barrier is size selective and charge selective; all component are negatively charged, as are plasma proteins)
Symptoms of advanced kidney disease?
Tiredness, peripheral oedema, SOB (pulmonary oedema and anaemia), nausea, fatigue, haematuria (visible or non visible)
Features of acute glomerulonephritis?
May be oedematous, hypertensive; may have cola/smoky urine, may be oliguric/anuric, may have systemic features (rash, eye symptoms, arthralgia, haemoptysis, hair/skin changes)
Features of nephrotic syndrome?
Swelling (over days/weeks); urine frothy (massive protein leak), creatinine may be normal (hence why PCR/ACR is helpful), BP can be normal/low/high if very overloaded (oncotic pressure falls).
Nephrotic vs nephritic?
- Nephrotic is podocyte injury, changed architecture to get scarring and deposition of matrix or other elements i.e. altered permability. Leaky, with low serum albumin, high urine protein, oedema and hypercholesterolaemia. Heavy proteinuria!
- Nephritic is inflammation, with reactive cell proliferation, breaks in GBM, crescent formation. Less leaky, but may see red cell casts. e.g. small vessel vasculitis. More “AKI” like. Haematuria. Still often have proteinuria but not nephrotic range. Usually immune, rapidly deteriorating
Which diseases are more “nephrotic” than “nephritic”?
MOST: Minimal change nephropathy, FSGS, membranous nephropathy, diabetic nephropathy, amyloidosis. SLE is either
Which diseases are more “nephritic” than “nephrotic”?
MOST: anti-GBM, small vessel vasculitis, post-streptococcal glomerulonephritis, MCGN. IgA nephropathy! SLE is either
Clues in history for kidney disease?
- FHx (dialysis, transplant, ADPKD)
- Personal history (HTN, DM (if have retinopathy then will have microvascular disease everywhere), gout, CVA/PVD
- Childhood UTI (some may cause renal scarring)
- Drug history!!! (NSAIDS, antibiotics, recreational)
- Problems in pregnancy (PET)
- Previous kidney stones, cystitis, LUTS, loin pain
- Systemic signs (suggesting inflammationa)
- Swollen ankles!
- Urinary abnormalities
- Occupational (heavy metals, toxins etc.), smoking!!!!!!
Features on exam for kidney disease?
Anaemia (low epo, pulmonary haemorrhage), rash/vasculitic lesions, fevers, arthral/myalgia, eye changes, oedmea, pulses and bruits for renovascular disease, fluid status (BP l+s), palpable kidneys, transplant kidneys, palpable bladder, AAA.
Causes of hyaline casts?
Precipitated Tamm-Horsfall protein; low flow/concentrated urine/acid can cause this; so seen in dehydration/heavy exercise in normal patients.
Categorising CKD?
G1/2/3a/3b/4/5 with ACR <3, 3-30 and >30 for A1/2/3. Corresponds to risk of adverse outcomes.
ACR interpretation?
Done in diabetics. Normal range 0-3.5; microalbuminuria >2.5 (M) or >3.5 (F); proteinuria >30. (A1/2/3). Nephrotic range >220.
Total urinary protein loss interpretation?
Nephrotic is >3.5g/24 hours. Normal loss is <150mg (T-HP and albumin). Sticks only detect albumin.
Tamm-Horsfall protein and hyaline casts?
Precipitates in tubules, according to flow, pH; get casts. In immune damage/inflammation, RBC/WBC pass through damaged GBM/tubules and stick to tubular cast to give cellular casts.
Light microscopy of fresh MSU re casts etc.
Red cell casts diagnostic of glomerular disease, white cell casts of interstitial nephritis, tubular debris in acute tubular necrosis.
Investigations in renal disease?
- U+E, FBC, LFTs, BG, CRP, coag, CK, bone.
- Urinalysis + MCS + PCR
- Renal US
- ECG (K+)
- CXR (systemic/cardiac/overload)
- ABG, MSSU, virology, urate, lactate, KUB (xray), urine biochemistry
- BIOPSY
Renal screen?
Looks for intrinsic causes of disease.
- GN screen: ANCA (MPO + PR3), anti-GBM, complement, ANA/ENA/Igs, ASO/cryoglobulins/RhF
- Myeloma screen: serum (+urine) free light chains/electrophoresis
- Virology (HBV/HIV/HCV)
Imaging of kidneys?
USS + Doppler first line, AXR-KUB for calcification , stones. IVU, CT, MR, nuclear medicine (GFR, excretion, scarring), angiography (RA stenosis). Remember to be wary of contrast! + BIOPSY
What to do if someone presents with very high potassium?
ECG, repeat bloods.
Findings in membranoproliferative glomerulonephritis?
Gives mixed nephrotic/nephritic syndrome. Low C3. C3 nephritic factor usually +ve (i.e. antibody to C3 convertase).
IgA nephropathy?
Most common cause of GN. IgA deposits in glomerulus, increased by concurrent URT infection; occurs in 2-3 days rather than weeks with post-streptococcal GN. Raised serum IgA; can do IgA/G/M electrophoresis
What is pulmonary-renal syndrome?
Bleeding in lungs and GN; usually Wegener’s (GPA) or Goodpasture’s. May be SLE or microscopic polyangitis.
What is crescentic GN?
A form of rapidly progressive GN (along with focal necrotising). Glomerular tuft compressed by surrounding hypercellular (macrophages, epithelial cells) in Bowman’s space. Crescents are not diagnostic of ANCA vasculitis, but do indicate severe glomerular injury
What is rapidly progressive GN?
Syndrome of glomerular haematuria (dysmorphic red cells or red cell casts), rapidly developing kidney failure, and glomerular necrosis with or without crescent development. Causes include IgA nephropathy, ANCA, HSP, SLE, post-infectious etc.
Which renal functions are principally affected in AKI?
Excretion of nitrogenous waste (raised urea) and fluid/salt homeostasis (overload, electrolyte disturbance)
Consequences of sudden loss of renal function?
- K+ rises; death/arrhythmia/muscle weakness
- Uraemic toxins accumulate. N+v, malaise, pericarditis/pleurisy, fits, coma. (and bleeding risk)
- Salt and H20 accumulate; get fluid overload and rapid death with pulmonary oedema
- Metabolic acidosis (kidney normally secretes H+). Get haemodynamic instability, cellular function disrupted. Can be fatal.
Stage 1 AKI?
Cr 1.5-1.9* baseline in 7 days, or increase of >26.4 in 48 hours. UO <0.5ml/kg for 6-12 hours
Stage 2 AKI?
Cr 2-2.9* baseline in 7 days; UO <0.5ml/kg for >12 hours.
Stage 3 AKI?
Cr >3* baseline in 7 days, reaching >354, dialysis. Or UO <0.3ml/kg for >24 hours or anuria for >12 hours.
Causes of pre-renal azotaemia?
- Volume depletion
- Low cardiac output (tamponade, massive PE, MI)
- Distributive (sepsis, ana, pancreatitis, hepatorenal)
- Vasoconstrictors (NSAIDs)
Effect of NSAIDs and ACEI on kidneys?
NSAIDs constrict aa; get reduced perfusion AND GFR; ACEI dilate efferent so perfusion normal but GFR drops. Neither are nephrotoxic as such but do decrease GFR, particularly if given together.
Tubulo-interstitial AKI?
Less likely to have protein and blood than in glomerular disease (as this is where they would be filtered)
Types of tubulointerstitial AKI?
- ATN (cells lining tubules)
- Tubular obstruction by casts (myoglobin, paraprotein, urate)
- Acute allergic interstitial nephritis. May get rash!
What is ATN?
Acute tubular necrosis. Proximal tubule cells work hardest (as with hepatocytes) (ie ‘return’ most of GFR) and are most vulnerable to ischaemia. Get cell death, blocked tubules, lower GFR, oligo/anuria. Recovery may take weeks or be incomplete
Causes of ATN?
- Ischaemia/hypotension (i.e. progression from persistent pre-renal azotaemia, renal artery stenosis.
- Toxins (aminoglycosides, cisplatin, contrast
Diagnosing ATN?
FENa >3% (fractional excretion of sodium) and presence of muddy casts (type of granular cast) on urinalysis. Can confirm with biopsy; necrosis and tubular obstruction.
Tubular obstruction by casts (a type of tubulointerstitial AKI)?
Can be paraprotein (free light chains clump with Tamm-Horsfall), myoglobinin from rhabdomyolysis, urate from TLS. If myoglobin, see DARK URINE and haematuria dipstick may be positive! Low flow favours precipitation so give IVT
Three types of rapidly progressve/crescentic glomerulonephritis?
- Immune complex GN (lupus, IgA, post-infectious)
- Anti GBM (if involves lung and kidney = Goodpasture’s syndrome).
- ANCA-associated vasculitis
HUS?
A microvascular cause of intrinsic AKI. Damage to endothelium by 0157 Shiga toxin/complement dysregulation; get microthrombi in response to damage, which ‘cut’ RBCs so see fragments (MAHA) and thrombocytopenia +/- anaemia. May have diarrhoea as precipitant
Cholesterol embolisation syndrome?
Another microvascular cause of intrinsic AKI; occlusion of microvasculature by atherosclerotic plaques; can be spontaneous or following arterial instrumentation!
Oliguria in AKI?
A feature of hypoperfusion and ATN specifically, but not oliguria reflects hypoperfusion (may be instrinsic/post) so IVT may not resolve it. Also, not all AKI oliguric. Recovering ATN often polyuric phase, relief of chronic obstruction can be polyuric. Means must push fluids or become volume deplete again!
AKI Ix?
Pre = fluids, post = USS etc. Intrinsic = CK, ANCA, electrophoresis, blood film, complement, DS DNA, biopsy (if suspect intrinsic,GN/interstitial nephritis cause other than ATN).
Indications for dialysis in AKI?
Refractory hyperkalaemia, pulmonary oedema, symptoms and signs of uraemia, acidosis. Also, removal of some toxic substances in OD.
How to give fluids in AKI?
If deplete, give bolus/challenge and reassess. Be cautious if overloaded/pulmonary oedema. Match input to output of previous hour. Do not just give according to creatinine; give according to fluid status.
What does/doesn’t get filtered in glomerulus?
Creatnine, glucose, inulin, K etc. all freely filtered; 75% myoglobin filtered (hence why rhabdomyoloysis causes cast formation and ruins kidneys); Hb and albumin <0.1%.
What is thin BM disease?
Inherited collagen defect; only diagnosed biopsy. Common cause of (asymptomatic) haematuria, along with IgA nephropathy.