Nephrology Flashcards
(111 cards)
1
Q
What are the two sets of capillary beds within kidneys?
A
Glomerular - high pressure, filtration
Peritubular - low hydrostatic pressure, fluid resorption
Renal artery 🡪 branches into interlobar arteries 🡪 arcuate arteries 🡪 interlobular arteries 🡪 afferent arterioles (approaching) 🡪 glomerular capillaries 🡪 efferent arterioles (exiting) 🡪 peritubular capillaries
2
Q
What is the physiological function of renin?
A
produced by the the juxta glomerular cells of the kidney
Converts angiotensinogen to angiotensin 1
Stimulus for release - baroreceptors of afferent arteriole, decreased NaCl in distal tubule detected by macula densa
3
Q
In which organ is ACE produced?
A
The lungs
Converts angiotension 1 to angiotension 2
4
Q
What are the physiological effects of angiotensin II?
A
Systemic – vasoconstriction (increase MAP)
Thirst
Posterior pituitary ADH release – promotes water reabsorption
Adrenal aldosterone secretion – sodium and water retention in DCT/CD
Renal
Construction of efferent > afferent arterioles – increases GFR
In higher doses – afferent and efferent constriction
Strongly promote NaCl and water reabsorption in PCT
5
Q
What are the physiological effects of aldosterone?
A
Secreted by zona glomerulosa of the adrenal cortex
Acts on the principal cells of cortical collecting tubule
Stimulates Na/K/ATPase pump on basolateral side of cortical collecting tubule AND increases sodium permeability on luminal side of the membrane (activates ENAC)
Stimulated = ↑ extracellular potassium levels, AngII
Net effects = retention of sodium, secretion of K+ and H+
6
Q
What is the primary defect in Alport’s disease?
A
Abnormal type 4 collagen - impaired glomerular basement membrane
Associated with haematuria (initially) followed by proteinuria and CKD, in addition to hearing loss and eye abnormalities
7
Q
Which of the following is NOT part of the filtrate in the nephron?
a. sodium
b. potassium
c. magnesium
d. calcium
A
d calcium
Calcium and free fatty acids not filtered as they are bound to plasma proteins
8
Q
Define GFR
A
Total volume of plasma leaving the glomerular capillaries and entering Bowman’s capsule
9
Q
Where are the juxtaglomerular cells located?
A
Sm ms cells in the afferent areriole
If decreased BP, will relax + release rennin
10
Q
Where are the cells of the macula densa located?
A
Distal convoluted tubule, sense NaCl levels
11
Q
What is absorbed in the proximal convoluted tubule?
A
Reabsorption of 65% of filtered Na+/K+/Ca2+/Mg2+
Reabsorption of 85% NaHCO3
Reabsorption of 100% of glucose and amino acids
Isosmotic reabsorption of H2O
12
Q
What is absorbed in the thin descending loop of Henle?
A
Water passively resorbed through aquaporins
13
Q
What is absorbed at the thick ascending loop of Henle?
A
Active reabsorption of 15-25% of filtered Na+/K+/Cl-
Secondary resorption of Ca2+ and Mg2
Loop diuretics, low K
14
Q
What is absorbed at the DCT?
A
Active reabsorption of 4-8% of filtered Na+ and Cl-
Ca2+ reabsorption under PTH control
Thiazide diuretics
15
Q
What is resorbed in the cortical collecting duct?
A
Na+ reabsorption (2-5%) coupled to K+ and H+ secretion
16
Q
What is resorbed in the medullary collecting duct?qq
A
Water resorption under ADH control
17
Q
True or false?
The nephron primarily regulates acid base through the secretion of bicarbonate and the resorption of H+
A
False
Basic principles
Two mechanisms of acid base control = resorption of bicarbonate + secretion of H+
Hydrogen ion secretion from tubule cells into the lumen is the key in reabsorption of HCO3- and the formation of a titratable acid (H+ bound to buffers such as HPO42-) and ammonium ions (NH4+)
Because loss of filtered HCO3- is the equivalent to addition of H+ to the body, all filtered bicarbonate should be absorbed before dietary H+ should be excreted
Resorption of HCO3- much more important than secretion of H+
In alkalosis 🡪 kidneys resorb less HCO3-
In acidosis 🡪 kidneys secrete additional H+ and do not excrete HCO3-
This occurs at all parts of the tubule except the ascending thin limb of the loop of Henle
18
Q
At what age to children achieve an adult GFR (approx 120 ml/min)?
A
2 years
19
Q
Which of the following is the most precise way of calculating GFR?
a. inulin clearance study
b. DTPA
c. EDTA
d. Schwartz method
A
Answer = A
GFR = the volume of a substance that can be cleared from plasma per unit time
OR
the volume presented to the nephrons during urine formation, typically in ml per minute
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198668/ - covers much of the material above, doesn’t go into detail regarding nuclear medicine techniques
https://tech.snmjournals.org/content/41/2/67 - this article is about nuclear medicine techniques for estimating GFR
Two main types:
Cr labelled EDTA
Tc labelled DTPA
Both considered reliable when estimating GFRs >30 ml/min
Complicated equations are then derived from multiple plasma samples - see link for further details
20
Q
You are seeing a 9 year old patient with haematuria and a recent URTI. Which of the following features would make IgA nephropathy MORE LIKELY than acute post streptococcal nephritis?
a. Onset of haematuria 8-14 days after URTI
b. hypertension
c. biochemical evidence of streptococcal infection
d. normal C3
A
A = d, normal C3
21
Q
What proportion of children with IgA nephropathy experience ESRD?
A
20-30%, takes till 15-20 years from disease onset
22
Q
Which of the following DOES NOT make Alport syndrome more likely?
a. male patient
b. microscopic haematuria becoming macroscopic with URTIs
c. anterior lenticonus
d. sensorineural hearing loss present from birth
A
d. = sensorineural hearing loss present from birth
Never congenital
Develops in the higher frequency hearing range then progressively worsens
Alport = defect in alpha chain of collagen type 4
COL4A1-6
Most commonly X-linked gene of COLA4 (85%)
23
Q
Which is the most common mode of inheritance for Alport’s disease?
A
X-linked
COLA5 (alpha chain of type 4 collagen)
24
Q
What is the most common presenting feature of Alport’s disease?
A
All patients have microscopic haematuria
25
You see a patient with persistent microscopic haematuria.
Microscopy and culture is otherwise negative. There is normal renal function and blood pressure. Renal tract ultrasound is also normal.
Audiogram and ophthalmic examination are normal.
What is the most likely diagnosis and what will your plan be?
Thin basement membrane disease
Yearly BP and urine PCR is warranted - overlap with Alport's, requires surveillance
26
A patient with a rapidly progressive glomerulonephritis undergoes renal biopsy.
Light microscopy shows diffuse mesangial proliferation and polymorphonuclear infiltration.
EM shows electron dense humps on epitheliam side of GBM ('starry sky')
Immunofluorescence shows 'lumpy bumpy' deposits of IgG and C3
What is the diagnosis?
This suggestive post streptococcal glomerulonephritis.
27
What is the benefit of treating patient's with APSGN with pencillin?
Does not reduce risk/severity of GN
Prevents spread of nephritogenic strain
28
A patient with progressive glomerulomephritis undergoes renal biopsy which shows 'wire loop' lesions.
What is the diagnosis?
SLE
Class I = minimal mesangial lupus nephritis (deposits on IF/EM only)
Class II = mesangial proliferative nephritis
Class III and IV = mesangial and endocapillary lesions (‘wire loop lesions’) 🡪 MOST COMMON
Class V = membranous lupus nephritis
Class VI = advanced sclerosing
Chronic = tubulointerstitial nephritis
29
A patient with facial rash, joint pain and renal disease develops haematuria, proteinuria and hypertension.
You suspect SLE nephritis.
What is the most likely class?
Class IV
Mild lupus nephritis (class I-II, some class III) = haematuria, normal renal function, proteinuria <1 g/24 hours
Class III (some) and ALL patients with class IV nephritis = haematuria, proteinuria, hypertension, reduced renal function, nephrotic syndrome, or acute renal failure
class V nephritis = nephrotic syndrome
30
What variant of GN is suggested by a renal biopsy with 'pauci-immune' crescentic GN?
ANCA associated vasculitis
Ab directed against neutrophil cytoplasmic Ag
cANCA = PR3 ANCA = granulomatosis with polyangiitis (GPA or Wegners)
pANCA = MPO ANCA = microscopic polyangiitis (MPA/renal limited vasculitis)
31
You see a patient with a history of extensive rhino-sinus disease and glomerulo-nephritis.
You send bloods for IF and ELISA looking for anti-neutrophil cytoplasmic antibodies. Which ANCA subtype will you expect to find?
PR3 = Wegener's or granulomatosis with polyangiitis
Pneumonic = Wegener was bad for PR
32
You see a patient who had a prodromal illness with fever, weight loss and arthralgia.
They have now developed levido reticularis and glomerulonephritis.
There is no upper resp involvement.
You suspect an ANCA associated vasculitis.
Which form of ANCA do you expect to find on ELISA?
ACNA - MPO
Pneumonic = MPO for microscopic polyangiitis
33
Which of the following organisms is NOT known to be associated with haemolytic uraemic syndrome?
a. Shiga toxin producing E.Coli
b. HIV
c. Salmonella
d. Neuraminidase producing streptococcus pneumoniae
e. Shigella dysenteriea
Answer = C, salmonella
Shiga toxin producing E.Coli: most common cause in Western countries, ~5% mortality in developed settings
Salmonella - not known to be associated
Neuraminidase producing E.Coli - higher mortality rate ~20%, often associated with complicated infections (empyema ect)
Shigella dysenteriea - most common organism in Asia and South Africa
34
Which of the following strategies is part of the management of haemolytic uraemic syndrome?
a. low threshold for transfusion of platelets
b. antibiotic directed against E.Coli O57:H7
c. immunomodulation with ciclosporin
d. strict use of washed blood products only
Answer = D
a = platelets consumed rapidly, not known to be helpful
b = antibiotics can promote toxin release from E.Coli, not recommended
c = not part of management, ciclosporin has been known to trigger HUS in transplant recipients
d = T antigen on RBCs (revealed by neuraminidase) drives illness in strept related HUS, only washed blood products should be used
35
A patient you see in clinic reports 5 distinct episodes of nephrotic syndrome in the past 12 months.
They have a urine protein creatinine ratio of 250.
You initiate high dose steroids and at day 15 they have dipsticks negative for protein for 3 consecutive days.
Which of the following terms accurately describes their nephrotic syndrome?
a. frequently relapsing
b. steroid resistant
c. FSGS
d. steroid dependant nephrotic syndrome
Answer = A, frequently relapsing
Remission = urine protein excretion < 4 mg/hr/m2 (<30 mg/mmol PCR), OR albustix 0/trace 3 consecutive days
Relapse = urine protein excretion > 40 mg/hr/m2 (>200 mg/mmol PCR), OR albustix >=3 for 3 consecutive days
Frequently relapsing = 2 or more times in the first 6/12 OR 4 or more times in any 12 months
Steroid-sensitive NS = clinical remission < 4 mg/hr/m2 (<30 mg/mmol PCR), OR albustix 0/trace 3 consecutive day after <4 weeks of steroid therapy
Steroid-dependent NS = 2 codnsecutive relapses whilst on steroid therapy or within 14 days of discontinuation of steroid therapy
Steroid-resistant NS = failure of proteinuria to resolve with at least 28 days of prednisolone at 60 mg/m2/day
36
Describe the features of Deny's drash syndrome
Wilm's tumour (90%)
Infant onset SRNS
Ambiguous genitalia
37
What is nephrotic range proteinuria?
Urine albumin creatinine ration >200 mg/mmol
38
What are the indication for biopsy in nephrotic syndrome?
Failure to respond to steroids
Age <1 or >12
Gross haematuria
Hypertension
Renal failure
39
What are the histopathological findings of minimal change disease?
Podocyte foot process effacement on EM
Will appear normal on light microscopy
40
What are the histological findings on FSGS?
LM = Focal sclerotic lesions
IF = stain IgM and C3 positive
EM - foot process effacement
41
You see a patient in clinic with nephrotic syndrome and hypertension.
Renal biopsy is performed with the following findings:
LM = mesangial proliferation, capillary wall thickening
EM = subendothelial deposits in the capillary wall, double contouring of BM
IF = C3 and lesser amounts of Ig
This is type 1 (immune complex mediated) membranoproliferative disease
Characterised by SUB ENDOTHELIAL DEPOSITS and IgG + C3 on IF
Membranoproliferative disease is a histological finding characterised by cellularity and BM thickening on LM, not a specific disease entity
Type 1/immune complex is more likely to be associated with infections (Hep B/C, strept, staphylococcus), SLE, cryoglobulinaemia
There is a type 3 which has features features of both
42
You see a patient in renal clinic who has nephrotic syndrome and hypertension.
They have a renal biopsy which has the following features:
LM = mesangial proliferation, cap wall thickening, BM thickened due to dense deposits
IF = C3 prominent, without concomitant Ig, continuous, dense, ribbon-like deposits along BM
This is type 2 (complement mediated) membranoproliferative disease
Membranoproliferative disease is a histological finding characterised by cellularity and BM thickening on LM, not a specific disease entity
Type 2 is mediated by deranged complement activation
Associated diseases include C3 nephropathy, dense deposit disease, C3GN
43
What disease is associated with mutations in the NPHS1 gene?
Finnish type congenital nephrotic syndrome
44
You review a patient who has severe hypokalaemia, hypomagnesaemia and metabolic acidosis associated with a mild viral illness around age 5.
What diagnosis would you suspect?
Gitelman's
45
. 8 month old boy presents with 3 weeks of polyuria, being treated as presumed UTI. Has failure to thrive.
Bloods:
Na 134
K 2.8
Chloride low
High bicarbonate
Serum Calcium and Mg NAD.
Urine calcium creatinine ratio elevated
Renal Ultrasound shows medullary calcification
What is the most likely diagnosis?
Barter syndrome
46
what are the rules for compensation of a metabolic acidosis ?
CO2 should go down by 1 for every 1 drop in bicarbonate
This is because respiratory compensation is rapid
47
what are the rules for compensation of a respiratory acidosis?
acute resp: every 10 increase in CO2 results in 1 increase of HCO3 by 1
chronic resp: for every 10 CO2 bicarbonate goes up by 4
48
what are the causes for increased ion gap metabolic acidosis?
49
what is the formula for calculating anion gap?
Na + K (+/-) - Cl - HCO3
50
type 2 renal tubular acidosis is located in which part of the nephron?
Proximal
Proximal assoc with urine acid <5.5 (acidified by distal parts of tubule) and high citrate in urine
51
Dysfunction in the cortical collecting ducts leads to which type of RTA?
Distal is type 1
52
You review a patient with acute renal injury and metabolic acidosis. You give a 1mmol/kg bicarbonate bolus, several hours after this the following results are obtained:
Urine pH 5.5
Serum bicarbonate 19
Which type of RTA is suggested by these results?
This is a type 2/proximal
Functionally this is a deficit in bicarbonate resorption
Fractional excretion of bicarbonate >15% would also be suggestive
See NZ slides
53
what is the mechanism for short stature in patients with a chronic metabolic acidosis?
Phosphate is used as a buffer when bicarbonate levels are chronically low
54
what type of RTA can cisplatin cause?
Proximal/type 2/bicarbonate resorption defect
55
which strain of bacteria is most commonly associated with HUS?
STEC (shiga toxin producing e coli)
E.Coli 0157:h7
56
Which of the following is NOT a poor prognostic indicator inHUS?
a) neutrophilia >20
b) CNS involvement
c) atypical HUS
d) Anuria for >2 weeks - increased risk of cortical necrosis and CKD
e) minimal colitis with rapid resolution
57
You are managing a child with HUS. Their sibling develops diarrhoea. What early management strategy has been shown to reduce the risk of subsequent renal failure?
IV fluid volume expansion has been shown to reduce risk of subsequent oligoanuric renal failure.
Loperamide and antiobiotics may increase risk of HUS
58
what are the management strategies for genetic/complement mediated HUS?
PLEX
Eculizumab (anti C5 monoclonal ab)
59
what is the significance of white cell casts
suggests acute interstitial nephritis
60
what makes up a normal anion gap?
For reference, a normal anion gap depends on the concentration of phosphate and albumin in the serum and ranges from 4 to 12 mmol/L
https://www.ncbi.nlm.nih.gov/books/NBK539757/#:~:text=For%20reference%2C%20a%20normal%20anion,acid%20and%2For%20decreased%20base.
61
why is normal anion gap metabolic acidosis also called hyperchloraemic metabolic acidosis?
The human body is very good at remaining balanced ionically under most scenarios. As a result, with loss of bicarbonate (the negatively charged ion), the negatively charged chloride (Cl) ion is displaced to the extracellular space
https://www.ncbi.nlm.nih.gov/books/NBK482340/#:~:text=Hyperchloremic%20metabolic%20acidosis%20is%20a,renal%20causes%2C%20and%20exogenous%20causes.
62
A patient with Lupus develops metabolic acidosis and chronic kidney impairment.
Their biochemical results are as follows:
pH 7.2 HCO3 18 CO2 30
Urine pH = 7.8
Serum K = 2.8
Urine calcium = HIGH
This is a type 1 (distal) renal tubular acidosis
Failure of H+ secretion into tubule = high urine pH
Failure to produce bicarbonate = systemic acidosis
63
what is the contribution of the proximal convoluted tubule to renal handling of acid base?
PCT = bicarbonate resorption
Carbonic anhydrase needed
Doesn't make new bicarbonate
So is serum bicarb is 13 the most you can get it to with this mechanism is 13
64
what is the contribution of the collecting duct to renal handling of acid base?
PRODUCES bicarbonate
Does this by excreting H+, driving the Henderson-Hassback equation to the left
65
The ureteric bud arises from the XXXXXXXXX and gives rise to the YYYYYYYYYY
This fuses with the metanephric mesenchyme, which goes on the become ZZZZZZ
XXXXX = wolfian duct
YYYYYY = collecting duct
ZZZZZZ= Bowman's capsule and most of the nephron
The ureteric bud arises from the XXXXXXXXX and gives rise to the YYYYYYYYYY
This fuses with the metanephric mesenchyme, which goes on the become ZZZZZZ
66
You review a patient in clinic. They had a normal birth and delivery and normal neonatal period.
Now at 12 months of age they have growth failure, metabolic acidosis , hypophosphatemia + rickets and rickets.
There urine has a pH <5.5, but has glucose, amino acids and citrate in it.
You notice the child is blonde and fair haired.
How will you diagnose the most likely disorder?
Blood: elevated WBC cystine levels
Now at 12 months of age they have growth failure, metabolic acidosis , hypophosphatemia + rickets and rickets. There urine has a pH <5.5, but has glucose, amino acids and citrate in it - these features suggests a proximal tubulopathy (renal Fanconi syndrome)
Blonde = fair hair is a clue to cysinosis
This is a lysosomal storage disorder (accumulation of cystine)
There is a treatment - cystaemine (mercaptamine)
See slide for extra renal manifestations
67
where is the nephron does acetylzolamide act?
Inhibits NaHCO3 resorption in the proximal tubule
68
where is the site of action of thiazide diuretics?
Thiazide diuretics exert their diuretic effect via blockage of the sodium-chloride (Na/Cl) channel in the proximal segment of the distal convoluted tubule (DCT). When the Na/Cl channel is blocked, decreased levels of sodium cross the luminal membrane, thus decreasing the action of the sodium-potassium (Na/K) pump and decreasing Na and water passage to the interstitium.[3]
https://www.ncbi.nlm.nih.gov/books/NBK532918/
69
what is the mechanism of action of amiloride?
Blocks the aldosterone -upregulated epithelial sodium channel (ENaC) in the collecting duct
70
What is the mechanism of action of spironalactone?
Aldosterone receptor antagonist so blocks aldosterone stimulated gene expression in the collecting duct
71
What portion of the nephron is most commonly affected by Barter's syndrome?
Thick ascending limb loop diuretic
72
What is the mechanism of hypercalciuria in Barter syndrome?
Persons with Bartter syndrome often have hypercalciuria. Normally, reabsorption of the negative chloride ions promotes a lumen-positive voltage, driving paracellular positive calcium and magnesium absorption. Continued reabsorption and secretion of the positive potassium ions into the lumen of the TALH also promotes reabsorption of the positive calcium ions through paracellular tight junctions. Dysfunction of the TALH chloride transporters prevents urine calcium reabsorption in the TALH. Excessive urine calcium excretion may be one factor in the nephrocalcinosis observed in these patients.
73
Which tubulopathy is associated with hypomagnesaemia/
Gitelman's
Is like being on thiazide
74
What are the common features of Barter's and Gitelman's syndrome
Hypokalaemia
Metabolic alkalosis
Elevated renin/aldosterone
Low to normal BP
Polyuria
Polydipsia
Salt-craving
75
What are the different clinical manifestations of ADH vs an aldosterone mediate disorder?
ADH: changes in Na concentration and osmolality
Aldosterone: blood pressure, potassium and pH
76
what is normal serum range for osmolality?
280-300 mOsm/Kg
77
what is the normal range for urine osmolality?
50-1200 mOsm/kg
<2 months: 150 - 600 mOsm/kg
Urine electrolytes and osmolality shouldn't be thought of as having 'normal' or 'abnormal' values, rather, as having appropriate or inappropriate values for serum levels
78
patient with hyponatraemia. Serum osmolality is high or normal. What is suggested?
Factitious result. Hyperglycaemia, hyperlipidaemia, hypoproteinaemia
79
You review a patient with hypernatraemia. There serum osmolality is 312 and urine osmolality is 80.
You administer desmopressin, urine osmolality 4 hours later is 85
What is the cause?
Nephrogenic diabetes insipidus
80
How long does microscopic haematuria persist after acute post streptococcal glomerulonephritis?
2 years
81
CASE: 10 YEAR OLD GIRL
A 10 year old girl presents with fever, sore throat and is incidentally found to have microscopic haematuria in her urine with a spot urine:protein creatinine ratio of 250 mmg/mmol. Complement is normal.
In 2 month's time she has ongoing UPCR of 250
Kidney biopsy shows IgA 3+ in mesangium
What is the next most appropriate course of action?
a. treat with ACEiE
b. steroids
c. mycophenolate motephil
d. list for transplant
e. trial of antibiotic treatment
STEM suggests IgA nephropathy
Management would be ACE-i or ARB for proteinuria
If proteinuria not reduced by 3-6 months would trial 6 months of steroids
82
What are the biopsy findings in Alport's nephropathy?
Split, thickened basement membrane with basket weave appearance
83
How is nephrotic range proteinuria defined (using UPCR)
>200 mg/mmol
84
How is remission defined in nephrotic syndrome?
Dipstick negative for protein for 3 days or UPCR <22
85
Define frequency relapsing nephrotic syndrome
=2 relapses after Tx first 6 months or >/= 3 relapses in any given 12 months
86
what is the genetic basis of WAGR
11p13 deletion
Loss of WT1 - renal features
Loss of PAX6 - aniridia
Wilm's tumour - 50% risk
Aniridia
Growth delay
Range of developmental delays
WT1 deletions by a different mechanism can cause Denys-Drash
87
what are the eye abnormalities associated with alport syndrome?
Anterior lenticonus (the 'capsule' surrounding the lens wears down resulting in conical disfiguration of the lens)
Dot and fleck retinopathy
88
what is the most common form of inheritance for Alport's nephritis?
X-linked
COL4A4 (alpha collagen 5)
Boys more severely affected
89
You are seeing a patient in renal clinic. They were referred by their GP with 12 months of microscopic haematuria.
They are a 12 year old male with a COL4A5 mutation.
There are 120 RBCs per high powered field and no significant microalbuminuria.
Will you
a. start ACE-i
b. observe
c. start ARB
d. start a diuretic
a. start ACE-i
b. observe
c. start ARB
d. start a diuretic
Correct answer is B
90
what single factor is most predictive of ESRD in patients with posterior urethral valves?
In a multivariate analysis, a nadir serum creatinine greater than 1.0 mg/dL (88.4 µmol/L) was most predictive of renal failure (OR 71, 95% 10 to 482) followed by bladder dysfunction (OR 8.9, 95% 1.1 to 73).
91
what are the macroscopic pathological findings in autosomal recessive polycystic kidney disease?
Enlarged kidneys
Innumerable tiny cysts
May also have hepatic fibrosis with biliary duct ectasia
In ADPKD would instead find enlarged kidneys with macrocysts
92
what is the gene mutation underlying most cases of autosomal dominant polycystic kidney disease?
a. fibrocystin
b. PKD1 (polycystin 1)
c. PKD2 (polycystin 2)
d. PBJ
The correct answer is b, PKD1
85% of patients have mutations mapping to PKD1 gene on the short arm of chromosome 16 (encodes polcystin, a transmembrane glycoprotein)
10-15% of ADPKD mutations may to the PKD2 gene on the long arm of chromosome 4, which encodes polycystin 2, a proposed non-selective cation channel
The gene for ARPKD encodes fibrocystin, a large protein (>4,000 amino acids) with multiple isoforms
93
A 14-year-old girl complains of tiredness. She has no significant past medical history and denies any medications. Apart from being thin, there are no abnormal findings on examination. Her blood pressure is 105/70 mmHg. Results of investigations are listed below. Serum biochemistry: sodium 138 mmol/L [135-145]; potassium 2.3 mmol/L [3.4-5.0]; chloride 85 mmol/L [103-109]; creatinine 0.10 mmol/L [0.06-0.12]. Arterial blood gases: pH 7.50 [7.34-7.45]; PaO2 95 mmHg [80-100]; PaCO2 42 mmHg [35-45]; bicarbonate 39 mmol/L [22-28]. Urinary biochemistry: sodium 30 mmol/L; potassium 42 mmol/L; chloride 13 mmol/L. The most likely explanation for these results is:
a) barter's
b) gitelman's
c) laxative abuse
d) bulaemia
For this adolescent, urine volume 700-1400ml/ per 24hrs…let’s say 1000ml for ease of calculation.
Her urinary chloride level should be at least 110 mmol/L. Her urinary chloride is very low (13)
Her urinary Na+ should be 40-220 (it is low 30)
Her urinary K+ should be 2.5-125 (it is normal at 42mmol/L)
The low Na+ represents hypovolaemia…but the chloride reflects the true degree of hypovolaemia (Na+ excreted with excess bicarbonate).
A: Bartter syndrome. Hypokalaemic metabolic alkalosis with hypercalcuria, high urinary chloride, normal BP. This patient has a low urinary chloride.
B: Occult diuretic use. Metabolic alkalosis, hypokalaemia, high urinary chloride, normal BP. This patient has a low urinary chloride.
C: Occult laxative use. Hypokalaemia, sodium, water depletion, metabolic alkalosis. This patient has a normal sodium.
D: Hyperaldosteronism. Common cause of secondary hypertension. Urinary loss of potassium, chloride, hypokalaemia, metabolic alkalosis. This is out as the patient is normotensive.
E: Self-induced vomiting. Patients are often emaciated. BP is low normal. Loss of chloride - metabolic alkalosis, mild renal insufficiency. Hypochloraemia with urinary chloride close to zero. Secondary hyperaldosteronism and renal loss of potassium. Urinary potassium usually >10mmol/L. Metabolic alkalsosis - renal excretion of sodium bicarbonate, so urinary sodium higher than chloride.
The correct answer is E.
94
Spot diagnosis: bilateral congenital cataracts, hypotonia in a neonate. Goes on to develop a Fanconi's anaemia
Lowe syndrome (the oculocerebrorenal syndrome of Lowe, OCRL) is a multisystem disorder characterised by anomalies affecting the eye, the nervous system and the kidney. It is a uncommon, panethnic, X-linked disease, with estimated prevalence in the general population of approximately 1 in 500,000. Bilateral cataract and severe hypotonia are present at birth. In the subsequent weeks or months, a proximal renal tubulopathy (Fanconi-type) becomes evident and the ocular picture may be complicated by glaucoma and cheloids. Psychomotor retardation is evident in childhood, while behavioural problems prevail and renal complications arise in adolescence. The mutation of the gene OCRL1 localized at Xq26.1, coding for the enzyme phosphatidylinositol (4,5) bisphosphate 5 phosphatase, PtdIns (4,5)P2, in the trans-Golgi network is responsible for the disease. Both enzymatic and molecular testing are available for confirmation of the diagnosis and for prenatal detection of the disease. The treatment includes: cataract extraction, glaucoma control, physical and speech therapy, use of drugs to address behavioural problems, and correction of the tubular acidosis and the bone disease with the use of bicarbonate, phosphate, potassium and water. Life span rarely exceeds 40 years.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1526415/
95
spot diagnosis: LMW proteinuria, hypercalciuria and hypophosphatemia rickets
No medications, no features of metabolic disorder, thought to be genetic
normal milestones and eyes
Dent's - genetic proximal tubulopathy, usually without the extra renal features seen in Lowe's
Dent's disease (OMIM #300009) refers to a heterogeneous group of X-linked disorders that have previously been reported as X-linked recessive nephrolithiasis, X-linked hypercalciuric hypophosphataemic rickets, or idiopathic low-molecular-weight proteinuria with hypercalciuria and nephrocalcinosis [1–6]. The disease is characterized by manifestations of proximal tubule (PT) dysfunction associated with hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure [7]. Low-molecular-weight (LMW) proteinuria represents the most consistent manifestation of Dent's disease, detected in almost all affected males and obligate female carriers. There is considerable inter- and intra-familial variability in the other manifestations of PT dysfunction, which may cause a renal Fanconi syndrome with hypophosphataemic rickets, as well as in the extent of nephrocalcinosis/nephrolithiasis. Dent's disease is a rare disorder, with around 250 affected families reported to date [8, 9].
96
what channel does frusemide act on?
NKCC2 in the loop of henle
97
what are the biochemical abnormalities seen in Barter's syndrome?
what mechanism underlies this?
Metabolic acidosis and hypokalaemia - due to activation of RAAS caused by volume contraction, means sodium is normal
Hypochloraemia (presumably because NKCC2 impaired)
Low volume state
Hypercalciuria - this is because potassium outflow from ROMK needed to stimulate paracellular transport of calcium
Polyuria, polydipsia and salt craving
98
how would you differentiate metabolic alkalosis due to GI/skin losses from those caused by Barters
Urine chloride - would be low if GI cause
99
which diuretic can be used to treat hypercalciuria?
Thiazide
NCCT transporter is linked to calcium secretion
100
spot diagnosis: rising creatinine, rash, joints pain and white cell casts in urinalysis
Previously well
Likely acute interstitial nephritis
May have flank pain from stretching of the renal capsule
101
You are seeing a patient with known nephrotic syndrome.
They are weaning down and are now on ~ 5 mg/ alternate days
They have relapsed with 4+ protein on albustix 3 days in a row.
The next course of action would be to:
a. start cyclophosphamide
b. start cyclosporine
c. do renal biopsy
d. increase prednisolone to 60 mg/m2/day
e. MMF
The answer is d. increase prednisolone to 60 mg/m2/day
https://www.rch.org.au/clinicalguide/guideline_index/Nephrotic_syndrome/
Discuss with nephrology if:
features suggesting diagnosis other than INS (see assessment section above)
severe, difficult to control oedema
elevated creatinine despite correction of any hypovolemia
not in remission after 4 weeks of steroid therapy
relapses (while taking steroids or within two weeks of cessation, >2 in first 6 months or >4 in 12 months)
steroid toxicity prompting consideration of alternative agent
102
spot diagnosis: progressive renal insufficiency, polyuria, polydipsia, bland urinary sediment
Nephronophthisis (ciliopathy)
https://emedicine.medscape.com/article/982359-clinical
103
what is the most common cause for hypertension in pre-school aged children?
From the RCH Hypertension CPG
Primary/essential hypertension accounts for the majority of hypertension in children >6 years old and is generally associated with obesity or a family history of hypertension
Secondary hypertension is more common in younger children (<6 years old) with renal disease being the most prevalent cause. This population is at greater risk of hypertensive emergencies due to an underlying condition
104
nephronophthisis + retinitis pigmentosa
senior-loken
105
nephronophthisis + cerebellar abnormalities
Joubert
106
nephronophthisis + obesity, polydactyl, poor night vision + tunnel vision
Bardet Biedel
107
you are reviewing a 7 year old female patient with steroid resistant nephrotic syndrome
They have a baseline creatinine of 150
Which of the following will NOT slow progression to ESRD?
a. control of hyperphosphatemia
b. BP control
c. EPO for anaemia
d. low protein diet
The answer is c. EPO for anaemia
See image
108
what is the MAJOR mechanism of solute removal in peritoneal dialysis?
Diffusion
2nd: convection/solute drag
109
a 10 year old patient on peritoneal dialysis presents to your emergency department with cloudy effluent in the PD drainage.
They feel mildly nauseous, are afebrile and have normal vital signs.
After collecting an appropriate sample, what antibiotics would you commence?
International guidelines suggest gram pos and negative cover
At RCH: ceftazidime, vancomycin
INTRAPERITONEAL
IV Abs if septic
Add fungal cover whilst on antibiotics
110
what is the primary mechanism of solute removal in haemofiltration?
Convection/solute drag
Haemofiltration - solute drag/hydrostatic pressure ect
Solutes are removed with the solvent at the same concentration as in plasma
Dilutent added subsequently to change plasma concentrations
Haemodialysis - uses diffusion and osmosis
111
which cells make EPO
Peritubular interstitial cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2384119/
