Renal/urology Flashcards
Haemoglobinuria / myoglobinuria in UA
No RBCs on microscopy but dipstick pos for blood
Confirm with urine ammonium sulfate test - precipitates haemoglobin but not myoglobin
HUS pathophysiology
- Thrombotic microangiopathy
- Most commonly by Shiga toxin (esp E Coli aka typical HUS)
- Less commonly by activation of alternate complement pathway (aka atypical HUS)
Non AKI causes of creatinine variations
- Low in infants
- Low in kids with low muscle mass (DMD, spina bifida)
- High in muscular adolescents
- High in rhabdomyolysis
- Drugs - probenecid, cimetidine, trimethoprim (high Cr due to impaired secretion)
Fractional excretion of sodium (FENa)
= [(UNa x PCr) / UCr x PNa)] x 100
- Measures % Na excreted in urine
- Can’t be accurately interpreted in setting of diuretics (consider FE-Urea in that case - <30%=azotemia)
- If <1% -> due to prerenal azotaemia
- If >1% -> due to intrinsic causes of AKI
Total body water
70-80% term infants
60% at 1 yr
50% for females after puberty (M stay at 60%)
Osmolarity v osmolality
- Osmolarity - number of osmotically-active particles (osmoles) PER VOLUME of solute (Osm/L)
- Osmolality - number of osmoles PER WEIGHT of solution (Osm/kg)
- Normal serum osmolality ~280 mOsm/kg
ADH
- Secreted by posterior pituitary
- Acts on late distal tubule and CD to increase water permeability
- Regulated by (among others)
1) Osmoreceptors in hypothalamus
2) Volume (stretch) receptors in left atrium and blood vessels - Strongest stimulant = low volume aka hypovolaemia
Clinical clues to hypovolaemia
Tachycardia
Narrowed pulse pressure
Orthostatic hypotension
Orthostatic tachycardia (increase of 15-20 beats)
Prolonged CR
Resting tachycardia with hypotension
Low central venous pressure
Liddle syndrome
Primary Na retention (affects principal cells of distal tubule and CD)
-> low renin and aldosterone levels
-> HTN
-> hypokalaemia metabolic alkalosis
Bartter and Gitelman - common features
Severe Na+ losses -> hypovolaemia
-> Elevated renin/aldosterone levels
-> Hypokalaemia and alkalosis
Rarely hypertensive due to increased prostaglandin production causing vasodilation of renal arterioles
Bartter syndrome
- AR inheritance
- Abnormal solute transport in thick aLOH
- Lose Na, Cl, Ca and Mg in urine
- Similar labs to LOOP DIURETICs
- Type 4 is associated with deafness
- Sometimes presents with stones or nephrocalcinosis in neonatal period or early childhood due to Na wasting and hypercalciuria
Gitelman syndrome
- Defect in Na/Cl cotransporter in early distal tubule
- Similar labs to THIAZIDE DIURETICs, but also have severe Mg wasting
- Symptoms milder than Bartter
- Usually present later in life with muscle weakness, cramps, sapsms
Bartter v Gitelman
- Both cause hypokalaemic metabolic alkalosis & salt wasting WITHOUT HTN
- Bartter - affects aLOH, sometimes associated with deafness, HYPERcalciuria, NORMAL/LOW Mg, clinically = LOOP diuretics
- Gitelman - affects distal convoluted tubule, HYPOcalciuria, HYPOmagnesaemia, clinically = THIAZIDE diuretics
Thiazide diuretics - urinary Ca
DECREASES urinary Ca (can be used to treat kidney stones) and INCREASES serum Ca
Loop diuretics - affect on urinary Ca
INCREASES urinary Ca and DECREASES serum Ca (can be used to treat hypercalcaemia)
RTA type 1
Defective H+ SECRETION from DISTAL tubule
- Low K+, sometimes low Na
- Hypercalciuria
- +ve urinary anion gap (Na + K - Cl)
- AR and AD forms
RTA type II
Inability to reabsorb HCO3 in PROXIMAL tubule
- Low K+, normal Na+
- Normal urine Ca
Anion gap equation
Na - (HCO3 + Cl)
Causes of HAGMA - MUDPILES
Methanol
Ureamia
DKA
Propylene glycol
Iron/isoniazide/inborn error
Lactic acidosis
Ethylene glycol
Salicylates
PUV - overview
- Obstructing membranous folds within the lumen of the posterior urethra.
- Caused by disruption in the normal embryologic development of the male urethra.
- Most common cause of chronic renal disease due to urinary tract obstruction in children.
PUV - presentation
- Usually antenatal - bilateral hydronephrosis, dilated bladder, dilated posterior urethra
- Postnatal - newborn with UTI, abdo distension, resp distress (lung hypoplasia)
- Infant - FTT, urosepsis, poor urinary stream, straining while voiding
- Older - UTIs, day and night incontinence, voiding dysfunction
PUV - complications
- VUR
- Bladder dysfunction
- Increased risk of CKD
PUV - diagnosis
Micturating cystourethrogram (MCUG)
PUV - mgmt
- Urgent urology consult
- IDC (NGT, not balloon)
- Manage sepsis, UEC abnormalities, uraemia, acidemia, fluid imbalance
- Ablation
Potter sequence
- Due to severe inutero oligohydramnios
- Positional limb deformities (club feet and hip dislocation)
- Typical facial appearance incl pseudoepicanthus, recessed chin, posteriorly rotated, flattened ears, flattened nose
- Pulmonary hypoplasia
Ureteropelvic junction (UPJ) obstruction description
- Partial or total intermittent blockage of urine flow that occurs where the ureter enters the kidney, resulting in hydronephrosis.
- Most common pathologic cause of congenital hydronephrosis
- Usually due to intrinsic narrowing of musculature between junction of the renal pelvis and ureter, but may be due to extrinsic compression
- More common in males and on left side
UPJ obstruction - presentation
- Usually identified on antenatal US - renal pelvis but not ureter dilated
- Infants - abdo mass (enlarged kidney), UTI, haematuria, FTT
- Older kids - intermittent flank pain and abdo pain (pain after drinking due to dilatation of renal pelvis)
UPJ obstruction - management
- Aimed at preservation of renal parenchyma and function
- Pyeloplasty if decrease function or significant dilatation
Renal embryology
Ureteric bud -> collecting system
Metanephric mesenchyme -> glomerulus and nephrons
Wk 9 - 1st nephrons
Wk 12 - urine excretion
Wk 36 - nephrogenesis complete (or 4 wks postnatally, whichever is sooner)
Urine osmolality (mOsm/kg) - neonates v kids
At birth - 500-600
6-12 mths - 1,200
Indications for renal imaging postnatally
Failure to urinate 1st 24 hrs
Low urine output
Weak urine stream
Suprapubic mass
HTN
Timing of postnatal renal US
After 48 hrs of age - before then will underestimate hydronephrosis due to physiological dehydration
Nocturnal enuresis overview
- Involuntary nighttime voiding after 5 yrs
- By 5 yrs, 90-95% of kids almost completely continent during the day and 80-85% at night
- Primary = nocturnal urinary control never achieved
Nocturnal enuresis - 1st line mx (30-60%) success
Restrict fluids after 6pm
Motivational therapy
Conditioning therapy – sensor alarm
Nocturnal enuresis - medical management
Desmopressin acetate
Oxybutinin
Nephrotic syndrome - most common pathologies
- Minimal change disease (MCD) - >70%
- Mesangiocapillary / membranoproliferative GN (MPGN) – 8%
- Focal segmental glomerulosclerosis (FSGS) – 7%
Nephrotic syndrome - presentation
Facial swelling
Proteinuria
HTN
+/- low C3 (MPGN, PIGN)
+/- strep titres positive (PIGN)
Complement levels in nephrotic sydnromes
Low C3 – MPGN, PIGN
Low C3 & C4 – lupus nephritis
Normal – idiopathic nephrotic syndrome
Minimal Change Disease (MCD) - key features
Typical features
- < 6 yrs
- No HTN, no haematuria
- Normal C3&C4
- Normal renal function
- Usually responds to glucocorticoid therapy in 8 wks
MPGN - key features
- Most common in 10-20 yrs
- Most present with nephrotic syndrome
- May also present with acute nephritic syndrome with gross haematuria or asymptomatic microscopic haematuria and proteinuria
- Renal function normal or decreased
- HTN common
- Often low C3
MPGN v PSGN
- Both may have haematuria, HTN, low C3, positive strep titres
- PSGN – improve within 2 mths
- MPGN – nephritic syndrome, proteinuria & low C3 persist
AIN causes
- Drug induced immune response (esp NSAIDs, antimicrobials, anticonvulsants)
- Infection
- SLE
AIN presentation
- Classic triad – fever, rash, arthralgia (only present in minority)
- Low grade haematuria and pyuria - typical
- WC casts and urinary eosinophils – suggestive but not diagnostic
AIN management
- Stop medication
- Supportive care
- Occasionally corticosteroids
RTA - key common feature
- Disorders of tubule characterised by NORMAL anion gap (hyperchloremic) metabolic acidosis with relatively well preserved GFR
- Either hypoK (type 1&2) or hyperK (type 4)
RTA type I (dRTA) - key features
= Defective H secretion from DISTAL tubule
- Urine pH > 5.5 (no H+ in urine)
- PCT reabsorbs all alkali including citrate (normally makes Ca soluble) therefore HIGH urinary Ca +/- nephrolithiasis, nephrocalcinosis
- Low K+, sometimes low Na+
- +ve urinary anion gap (equation = Na + (K - Cl))
- NO FANCONI syndrome
- AR and AD forms
- Seen in Sjogren’s syndrome, SLE, primary biliary cirrhosis, autoimmune hepatitis
- TREATMENT - alkali and K+ replacement
RTA type II (pRTA) - key features
= Wasting HCO3 in PROXIMAL tubule (aka inability to reabsorb)
- Urine pH < 5.5 (distal tubules secrete excess H+)
- Low K+, normal Na+
- Normal urine Ca - no renal stones
- Associated with Fanconi syndrome (PAGU - phosphaturia, aminoaciduria, uricaciduria, glycosuria)
- Also seen in Myeloma, drugs (tenofovir, acetazolamide)
- TREATMENT - alkali (large doses) and K+ replacement
RTA type IV (aldosterone)
- Decreased production or diminished responsiveness of CD to aldosterone
- Most common type
- Present with HYPERkalaemia
- Associated with DM (most common), NSAIDs, ACE-I, calcineurin inhibitors (cyclosporine and tacrolimus), K sparing diuretics, high dose heparin
- MANAGEMENT
- if normotensive, fudrocortisone (mineralcorticoid)
- if hypertensive - thiazide or loop diuretic -> increases distal delivery of Na causing urinary secretion of H+ and K+
HUS triad
- Microantiopathic haemolytic anaemia
- Thrombocytopania
- AKI
HUS causes
- Infection, drugs, genetics, systemic
- Most common - E Coli (shiga like toxin O157:H7) - diarrhoea
- 2nd most common - strep pneumonia
- Other countries - Shigella toxin
HUS presentation
- Fever (low grade), N&V, abdo pain, BLOODY diarrhoea
- HUS at ~6 days -> increasing pallor and AKI
- Anaemia, low plts, hyperK+
- CNS involvement (sz (20%), encephalopathy) due to microthrombi
HUS diagnosis/labs
- Haemolytic anaemia (PT and PTT normal, cf DIC)
- High WCC
- LOW plts
- Schistocytes (fragments) on urine microscopy DIAGNOSTIC
- Coombs neg (unless associated with strep pneumo - empyema etc)
HUS treatment
Supportive care and dialysis:
- IVH
- Control HTN
- Transfusions (RBC, not plts) + electrolytes
- 50% need 2/52 dialysis
- Antibiotics contraindicated
HUS recovery
- Plts recover 1st, then AKI, then anaemia
- Worse prognosis if strep pneumonia
- Genetic form relapse and remit with a poorer prognosis and have low C3 (Eculizumab for genetic)
Poor prognostic features HUS
- Anuria > 2 wks
- Initial neutrophil count > 20K cells/uL
- Coma on admission
- Atypical forms (diarrhoeal better)
Age at which GFR ~reaches adult value?
2 yrs
Electrolyte abnormality associated with unilateral renal artery stenosis and why
Hypokalaeamia
Due to activation of RAAS -> aldosterone causes Na reabsorption and K secretion (aka hypoK+)
What is nephrotic syndrome?
- Damage to GBM -> causes protein loss
- Triad of proteinuria, hypoalbuminaemia and oedema
- May have hyperlipidaemia due to liver’s compensatory synthesis of proteins (incl albumin and lipoproteins) in response to hypoalbuminaemia
- May have microscopic haematuria
- Diagnostic criteria:
- Proteinuria (dipstick 3-4+ or Ur P/Cr ratio >0.2 gm/mmol (200 mg/mmol)
- Hypoalbuminaemia (<25 g/L)
Acute management for nephrotic syndrome
- Admit
- Treat sepsis if present (high risk of infection)
- Manage oedema -> 1) no added salt 2) daily wts 3) daily dipstick 4) strict fluid balance 5) monitor input and output 6) +/- albumin infusion 7) +/- frusemide
- Steroids (defer live vaccines while on high dose steroids)
- Prophylaxis against infection
Complications of nephrotic syndrome
- Infection - due to IgG losses, steroids, oedema (esp SBP, cellulitis, sinusitis, pneumonia)
- Thrombotic disease - due to hypercoagulable state and haemostatic abnormalities
- Oedema, with risk of anascara (massive generalised oedema)
- AKI -> CKD
- Hyperlipidaemia
- Cataracts and osteopaenia if long term steroid use
Nephritic syndrome - core features
- AKI
- Haematuria (with RBC casts and dysmorphic RBCs)
- HTN
- Oedema
+ Oliguria
+ Variable proteinuria
Commonest nephrotic and commonest nephritic syndromes
Nephrotic - MCD
Nephritic - IgA nephropathy
Nephritic syndromes with LOW complement levels + DDx
Nephritic syndromes
- PIGN
- Membranoprolifiterative GN
- SLE
Ddx
- Subacute bacterial endocarditis
- Complement mediated thrombotic microangiopathy
- Shunt nephritis
Nephritic syndromes with NORMAL complement levels
- IgA nephropathy
- IgA vasculitis (HSP)
- Pulmonary-renal diseases eg anti-glomerular basement membrane disease with pulm haemorrhage
- Granulomatosis with polyangitis
Conditions with nephritic urine sediment
Nephritic urine sediment = RBC casts, WBC or granules
Conditions:
- IgA nephropathy
- PIGN
- Membranoproliferative GN
- SLE
- Rapidly progressive GN
Tubular reabsorption of Na and water
Na
- 70% PCT
- 25% aLOH
- 5% DCT
- 1-2% CD (supported by aldosterone)
Water - independent of Na
- through ADH and aquaporin channels in CD
Where ions are absorbed in renal tubules
Diuretics - general mechanism of action
- Inhibit tubular Na reabsorption
- Causes secondary hyperaldosteronism -> low K, low H -> hypokalaemia and metabolic alkalosis
- K sparing diuretics (aldosterone antagonists) -> K and H retention -> hyperkalaemia, metabolic acidosis
Proximal convoluted tubule
- Reabsorbs 65% Na (Na-H)
- Key area for regeneration of HCO3 (via carbonic anhydrase)
- Na reabsorption coupled to reabsorption of glucose (SGLT), amino acids, phosphate, uric acid
- Defect causes RTA type II (proximal, impaired HCO3 regeneration)
Barrter syndrome - overview
- Defect in Na reabsorption in TAL of LOH
- Presents with metabolic alkalosis and hypokalaemia with LOW to NORMAL BP
- HIGH urinary Ca
- Multiple types/genes
- Type 4 associated with SNHL
- May have normal to low Mg
- Usually presents young
Frusemide - site and MOA
Inhibits NKCC2 transporter in TAL
Therefore also inhibits paracellular reabsorption of Ca and Mg aka HYPOcalaemia
Site and MOA Thiazides
- DTC - inhibits NaCl cotransporter (NCCT)
- Causes upregulation of NKCC2 in TAL, leading to Ca reabsorption aka HYPERcalaemia
- Gitelman syndrome also due to impaired NCCT (hence similar affects)
Gitelman
- Impaired Na reabsorption by NCCT (NaCl cotransporter) in DCT
- Similar to Thiazide
- Presents with hypokalaemic metabolic alkalosis (highish bicarb) AND hypomagnesaemia AND lowish BP
- LOW urinary Ca (due to reuptake of Ca++ in TAL)
- Presents older, sometimes with tetany due to low Mg
Causes of metabolic alkalosis with hypoK
- Bartter, Gitelman (will have low BP)
- Hyperaldosteronism (will have high BP)
- Chronic vomiting (will have low Cl due to increased NaCl reabsorption)
- Diuretic abuse (variable urinary Cl levels - depends on time of use)
Water reabsorption in the collecting duct
- Principal cells contain AQP2 (reabsorb water)
- ADH moves AQP2 from endosomes to the otherwise water impermeable luminal surface
Diabetes insipidus (excessive water loss) - types
- Central - vasopressin deficiency
- Nephrogenic - kidneys fail to respond to ADH
- Lithium - nephrogenic DI due to decreased expression of AQP2 genes
Action of Vasopressin receptors
V1 - located on vascular smooth muscle - cases vasoconstriction, increases SVR and increases BP
V2 - located on renal tubular cells - mediate water absorption through activating AQP2 channels
RAAS overview
- Macula densa cells in the DCT sense urinary Na and Cl -> when low stimulates juxtaglomerular cells
- JG cells on afferent arterioles -> secrete renin
- Renin cleaves angiotensinogen (liver) -> AGI
- Angiotensin converting enzyme (ACE) in lung cleaves AI -> AII
- AII = vasoconstrictor + increases aldosterone secretion
- Nb AII constricts efferent arterioles > afferent
- ACEI and ARB decrease intraglomerular pressure and therefore filtration (make less urine) -> less proteinuria BUT also may have resultant rise in creatinine
Aldosterone action
- Secreted by the zona glomerulosa of adrenal cortex
- Causes Na reabsorption + K & H excretion
- Upregulates basolateral Na-K-ATPase - causes concentration gradient with low intracellular Na
- Upregulates epithelial Na channel (ENaCs - increases apical membrane permeability for Na+
- Intraluminal movement of Na causes K secretion
- Intraluminal negativity causes H secretion by alpha intercalated cells
Cells in DCT
90% principal cells
10% - alpha (acid) and beta (bicarb) intercalated cells
How hyper K+ potentiates metabolic acidosis
- Excess K+ enters the cell and in exchange H+ is secreted
- K+ competes with H+ for secretion at collecting duct
- HyperK decreases renal ammonia production and so inhibits H+ excretion (ammonia is the chief buffer for H+)
How hypoK potentiates alkalosis
Augments H-K-ATPase pumps in the collecting duct (type A intercalated cells) which secrete H+ and reabsorb K+
Pathophysiology of hyperPTH in CKD
- Phosphate retention (initial trigger)
- Decreased Ca concentration
- Decreased calcitriol concentration
- Increased FGF 23 concentration
- Reduced expression of CaSR, FGF23 receptors and klotho (co-receptors for FGF23)
Proteinuria & albuminuria - levels
Types of GN
GN - investigations
PIGN - management
Fluid/salt retention
Diuretics - frusemide
Antihypertensives - frusemide, CCB +/- ACEI
Proteinuria/haematuria may persist for 3-4 mths
Recheck C3 in 8 wks - if post infective will resolve in 8 wks (if still low ?MPGN)
IgA nephropathy - treatment
HSP (IgA vasulitis) treatment
ANCA associated vasculitis - types
ANCA-associated vasculitis - overview
Tubular channels
Fanconi syndrome - causes
Cystinosis - overview
- Storage disorder
- AR
- Defect in CTNS gene (chr 17) - encodes cystinosin protein (cystine transport protein)
- > 50 diff mutations, single large gene deletion in ~50%
Cystinosis - management
14 yr boy, seizures, liver disease, renal calculi
4 mth, Vit D resistant rickets, renal calculi. Elevated cysteine levels in leuks.
8 yr boy, polyuria, microscopic haematuria, abdominal pain
