Nephrology Flashcards
Differences in urine microscopy comparing Acute tubular necrosis and acute interstitial nephritis?
ATN demonstrates muddy brown casts and/or tubular interstitial cells
Low grade haematuria and pyuria are typical of AIN; white cell casts and urinary eosinophils are suggestive of AIN but not diagnostic.
What does FeNa over 2% more suggestive of?
Either excess sodium is lost due to tubular damage, or the damaged glomeruli result in hypovolemia resulting in the normal response of sodium wasting
ADH is released by the posterior pituitary in response to what?
How big or little the cells are - in response to plasma osmolality
How does vasopressin work?
Binds to tube receptor, increases cAMP and increases aquaporins leading to increased reabsorption of water
What is the gene and mode of inheritance of diabetes insipidus?
AVPR2 gene - X linked recessive (mothers may be mildly symptomatic)
Can also be related to Aquaporin 2 upregulation - Autosomal
How does Fanconi syndrome present?
Limited reabsorption in phosphate (rickets), bicarb, water, Hypouricaemia, Amnicoaciduria
What does carbonic anhydrase in the renal tubules do?
It breaks down H2CO3 into CO2 + H20 and this allows passive transfer of CO@ and H20 into the basolateral cell
What drugs can cause Fanconi syndrome?
Gentamicin, Cisplatnisum, Ifosphamide
What are some inherited causes of Fanconi syndrome?
Cystinosis, Dent’s and Lowe’s syndrome
What are the two main electrolytes absorbed in the PCT?
Na and HCO2
Whats a normal anion gap?
Na + K) - (Cl+HCO3
7-13
SLCA4 gene can cause
Distal RTA (type I)
Major way of differentiating distal and proximal RTA?
Distal - urine PH alkalotic and hypercalcuria
Proximal - normal pH
Distal RTA is more likely to be genetic cause - what other features might you seen
Sensorineural hearing loss
What is the major electrolyte anomaly that helps differentiate Type IV RTA?
High Potassium
Hypokalamia, hypochloraemia and metabolic alkalosis?
Barrter’s Syndrome
Where is the anomaly in Barrter’s syndrome?
Impairment in Na+ and Cl- reabsorption in the thick ascending limb of loop of Henle.
Often anomaly in NKCC2 transporter associated with SLC12A1
You urinate sodium and chloride; in response renina nd aldosterone is secreted and you urinate more K+ in response to losing Na+
Barter’s syndrome is like effect from which diuretic?
Frusemide
Frusemide blocks NKCC2 chanel
In Frusemide, complication is
Hypochloraemic, hypokalaemic, Hypercalciuric
How do you treat Bartter’s syndrome?
You can treat with anti-prostaglandins (NSAIDS - indomethacin)
What are potassium sparing diuretics?
Spironlactone and Amiloride
What are the renal actions of prostaglandins?
- Increase renal blood flow
- Increase GFR
- Decrease sodium reabsorption at TAL/LoH
- Increase renin secretion
- Increase water excretion
Where is the pathology with Gitelman syndrome?
Diminished NaCl transport in the distal CT (like thiazides)
What is the 2 major serum anomaly and 1 major urine anomaly that may help you differentiate Barrters syndrome and Gitelman?
Gitelman you have low serum Mg and Low serum K+ and different to Bartters - in Gitelman you have low Urine Ca
NCCT gene associated with ______ syndrome
Gitelman syndrome
Angiotensin more so acts to constrict ________
whereas prostaglandins act to dilate the _____
Angiotensin more so acts to constrict Efferent artieroles
whereas prostaglandins act to dilate the Afferent arterioles
Aldosterone acts to do what?
It’s main action is to bind to the mineralocorticoid receptor (in the collecting duct); Causes production of ENaC (epithelial sodium channels) and also increases the Na-K-ATPASE channel and also increases excretion of potassium
How does Spironlactone and Amilaride work?
Spironlactone - works to block the Mineralocorticoid steroid receptor
Amilaride acts to block ENac
What is Liddle syndrome genetically?
Causes gain of function of ENaC (keeps it on)
Autosomal dominant
How does Liddle’s present?
Hypokalamia, low plasma renin and aldosterone levels, hypertension and metabolic alkalosis
Thus which antihypertensive does Liddle’s syndrome react well too?
Amiloride - because it blocks the ENaC
Which diuretic blocks the NKCC2?
Frusemide
Which diuretic blocks the NCCT?
Thiazide
What are the three most common types of stones?
1) Calcium Oxalate (50-65%)
2) Calcium Phosphate (14-30%)
3) Struvite (Magnesium, ammonium phsophate) 13%
Which stone is radiolucent on XRAY?
Uric acid
Although Cysteine and Xanthine stones stones are slightly opaque and can be difficult to see
Low citrate, low urine volume and pancreatic insufficiency is a risk factor for which type of stone?
Calcium Oxalate
Primary hyperparathyroidism, distal RTA is a risk factor for which type of stone?
Calcium Phosphate
Which stones are associated with urease positive UTI (proteus, Pseudomonas, klebsiella, Serratia, Cirtobacter, Morganella)?
Struvite stones
Urinary alkalinisation and excessive ammonia production -> precipitation of struvite (Mg-ammonia-P04) and CaP04
Lesch Nyhan and G6PD is associated with ______ stones
Uric acid stones
Also short gut syndrome (due to chronic dehydration and acidosis)
How do you treat Ca stones?
Do not treat with NaHC03 as increased Na will increase Ca urinary excretion (use K-citrate to alkalose instead)
What are the causes of hyperoxaluria?
Primary and Secondary
Primary hyperoxaluria a rare metabolic condition -> mutation in liver enzymes which enhances conversion of glyoxylate to oxalate (poor prognosis)
Secondary hyperoxaluria due to increased intake of oxalate, pyridoxine deficiency and those with intestinal malabsorption
Hyperoxaluria occurs with disorders such as IBD, pancreatic insufficiency and biliary disease. It is precipitated by fat malabsorption.
Please describe enteric hyperoxaluria
- There is GI malabsorption of fatty acids, which bind intraluminal Ca and form salts that are freely excreted in feces
- Normally Ca forms a complex with oxalate to decrease oxalate absorption but if Ca is unavailable there is increased absorption of unbound oxalate
Cannot treat hypercalciuria with low Ca diet, as oxalate and Ca compete for absorption: if decrease Ca absorption (from reduction in diet or excretion with FAs) will just get oxalate absorption and oxalate stones instead
How do you treat Calcium Oxalate stones that occur due to secondary hyperoxaluria?
Cannot treat with low dose Ca diet
Increase fluid intake, moderate oxalate restriction, low fat diet, high dose pyridoxine and RDA for calcium
How does hypocitrituria predispose to stones?
Low excretion of citrate, which usually increased the solubility of Ca in urine -> more Ca precipitation.
Thus, chronic diarrhoea, intestinal malabsorption and RTA (acidotic urine) may -> hypocitruria
Name the disease:
X-linked renal tubular disorder, associated with proteinuria, hypercalciuria and nephrocalcinosis
Dent’s disease
Name the disease:
CLCN5 gene (X-chromosome)_
Dent’s disease
Normally a protein expressed in the proximal tubular cells
Cysteinuria is an autosomal recessive disorder of the epithelial cells of the renal tubule that prevents absorption of the four basic AAs _______________ therefore -> urinary excretion of these
Cystine, ornithine, Lysine, arginine
Think COLA
How do you treat Cysteinuria?
- Na increases excretion of cystine therefore reducing dietary Na can treat cystine stones
- Alkalisation of urine (pH 7.5) with potassium citrate
- We use penicillamine in Australia to form a pencillamine-cysteine complex which is more soluble
Uric acid, cystine, and calcium oxalate stones tend to form in _____ urine, whereas struvite (magnesium ammonium phosphate) and calcium phosphate stones form in _______ urine
Uric acid, cystine, and calcium oxalate stones tend to form in acidic urine (pH <5), whereas struvite (magnesium ammonium phosphate) and calcium phosphate stones form in alkaline urine (pH>6)
4 key features of Nephrotic syndrome?
- HypoAlbuminaemia
- Proteinuria (protein:creatine >200mg/mmol)
- Peripheral oedema
- Hyperlipidaemia
Nephrotic syndrome is a ___ cell mediated disease
T cell mediated disease; thus responds to steroids and cyclophosphamide
Indications for biopsy in nephrotic syndrome:
- Atypical features (not 1-12yo, elevated creatinine)
- Non-responsive to medication (30 days +/- pulse methylpred
> __% of typical NS will respond to steroid
___% of the remaining will go onto have a relapse
__% of the responders will have frequent relapses (2 in first 6 months, 4 in 12 months)
> 90% of typical NS will respond to steroid
80% of the remaining will go onto have a relapse
50% of the responders will have frequent relapses (2 in first 6 months, 4 in 12 months)
Minimal change disease -> ______ -> ______ are probably a spectrum of disease on histology
Minimal change disease -> Mesangial hypercellularity -> FSGS are probably a spectrum of disease on histology
______ is helpful in steroid sensitive disease; but nowadays we use ______
Cyclophosphamide, but nowadays we use Calcineurin inhibitor (CSA or tac - tac preferred over CSA now)
Also can consider adding on Levamisole to Pred first
SE of Cyclophosphamide: hairloss, leukopenia, hemorrhagic cystitis
If steroid RESISTANT -> trial calcineurin inhibitor
Rituximab (anti-CD20) now proven to be effective in steroid sensitive NS or Steroid resistant NS?
Steroid sensitive NS
Alport syndrome is due a defect in which protein?
Type IV collagen in the GBM (thin GBM)
What is the pathognomonic eye finding in Alport syndrome?
Bonus marks for other findings too!
Pathognomonic - Anterior Lenticonus
Other findings:
- Retinal changes (dot and fleck retinopathy)
- Corneal damage
Causes of increased anion gap acidosis?
MUDPILES
Methanol/metformin/disease Uraemia Diabetic ketoacidosis Paraldehyde Isoniazid/iron Lactate Ethylene glycol/ethanol Salicylates
LTKR Lactate Toxin Ketones Renal
Complete the sentence on how the kidneys primarily participate in acid base balance:
Bicarbonate reabsoprtion from the _______________ with acid secretion from the ___________________-
Bicarbonate reabsoprtion from the proximal tubule with acid secretion from the collecting duct alpha intercalated cells
What kind of RTA does cisplatin cause?
Proximal tubule RTA (Type 2)
Late stages of ureteric bud involvement involves?
Collecting duct
ischaemia/drowning affects which region of the nephron the most?
Loop of Henle and proximal tubule
These areas need high O2 requirement
What are the congenital causes of Fanconi syndrome:
- In neonate?
- In infant?
- In childhood?
Neonatae - Galactosemia, Mitochondrial disorder, Tyrosinaemia
Infant - Fructosemia, cystinosis, Fanconi-Bickel syndrome, Lowe syndrome
Childhood - Dent’s disease, Wilson’s disease, cystinosis
How do you treat Cystinosis
Cystaemine (Mercaptamine), free access to water
Which diuretic works in the proximal tubule?
Acetazolamide
Carbonic anhydrase inhibitor; causes increased wasting of sodium
Which two diuretics can lead to metabolic acidoses with long term use?
Spironlactone and acetazolamide
Think of Acetazolamide causing Type 2 RTA and Spiro causing Type I RTA
90% of mutation with Nephrogenic DI are in the ADH receptor (_______); the inheritance pattern is ______
AVPR2 gene; X linked recessive
Timeline of resolution of C3, Proteinuria, Hypertension and haematuria in PSN?
- Hypertension for upto 2 weeks
- Microhaematuria can persist upto 1mo (but Gross Haem should resolve by 2-4 weeks)
- C3 should improve by 2mo
- Proteinuria can persist upto 6mo (but should be improving)
What do you see in kidney biopsy in PSGN?
Infiltrating neutrophils in the glomerular capillaries
Why is C3 low in PSGN?
Due to activation of alternate pathway
What are the findings of Membranoproliferative GN on kidney biopsy?
Double contouring of glomerular basement membrane on kidney biopsy (Spliti
What is the glomerular finding in Alport syndrome?
Basket weave appearance of glomerular basement membrane with some splitting
COL4A5 associated with…
Alport syndrome
Kids with nephrotic syndrome are more coagulable because….
Reduced levels of antithrombin III (lost in urine)
What is the disorder?
Later, the glomeruli may develop mesangial proliferation and capillary wall thickening, leading to progressive glomerular sclerosis. Tubular atrophy, interstitial inflammation and fibrosis, and lipid-containing tubular or interstitial cells, called foam cells, develop as the disease progresses.
In most patients, electron microscopy reveals diffuse thickening, thinning, splitting, and layering of the glomerular and tubular basement membranes
Alport syndrome
All patients with Alport syndrome have …
Asymptomatic microscopic hematuria
Single or recurrent episodes of gross hematuria commonly occurring 1-2 days after an upper respiratory infection are seen in approximately 50% of patients
What are the occular anomalies seen with Alport Syndrome?
Ocular abnormalities, which occur in 30–40% of patients with X-linked AS, include anterior lenticonus
Which biologic can help you manage atypical HUS?
Ecluzimab
How do you differentiate Gitelman and Barrters?
Magnesium and calcium
Gitelman’s have low serum magnesium and typically reduced/normal urinary calcium.
Barrter’s have increased urinary calcium.
Barrter’s traditionally also affects slightly younger children
Nephrogenesis occurs until what age?
36 weeks
Anti-histone antibody is associated with?
Drug induced lupus
What biological medication can be used to manage HUS?
Ecluzimab
If complement doesnt normalise within 3 months of PSGN -> what GN do you worry about?
Membranoproliferative - MPGN
What is the triad of prune belly syndrome?
1) deficient abdominal muscles,
2) undescended testes, a
3) urinary tract abnormalities probably results from severe urethral obstruction in fetal life
What is MAG3 scan useful for?
It is useful for detecting obstruction in the kidney -> you insert dye and see how it travels down the kidney and is excreted.
Can be helpful in detecting obstruction in duplex kidneys
Similar to DTPA but [referred in neonates?
What is DMSA scan used for?
Looking for scarring and kidney function/damage
What is the renal function in a unilateral MCKD?
The affected kidney has no function, but the other way does enough so normal renal function.
What drug inhibits the terminal compliment pathway?
Eculizumab (used for atypical HUS)
What is the type of GN?
Nephrotic syndrome that is not responsive to steroids…. after 2 months
FSGS
Congenital nephrotic syndorme is due to abnormality in which gene?
Nephrin gene (NPHS1)
Fanconi syndrome + cataracts + neurological symptoms =
Lowe syndrome
oculocerebrorenal syndrome
