Nephrology Flashcards
What are the two sets of capillary beds within kidneys?
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
What is the physiological function of renin?
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
In which organ is ACE produced?
The lungs
Converts angiotension 1 to angiotension 2
What are the physiological effects of angiotensin II?
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
What are the physiological effects of aldosterone?
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+
What is the primary defect in Alport’s disease?
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
Which of the following is NOT part of the filtrate in the nephron?
a. sodium
b. potassium
c. magnesium
d. calcium
d calcium
Calcium and free fatty acids not filtered as they are bound to plasma proteins
Define GFR
Total volume of plasma leaving the glomerular capillaries and entering Bowman’s capsule
Where are the juxtaglomerular cells located?
Sm ms cells in the afferent areriole
If decreased BP, will relax + release rennin
Where are the cells of the macula densa located?
Distal convoluted tubule, sense NaCl levels
What is absorbed in the proximal convoluted tubule?
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
What is absorbed in the thin descending loop of Henle?
Water passively resorbed through aquaporins
What is absorbed at the thick ascending loop of Henle?
Active reabsorption of 15-25% of filtered Na+/K+/Cl-
Secondary resorption of Ca2+ and Mg2
Loop diuretics, low K
What is absorbed at the DCT?
Active reabsorption of 4-8% of filtered Na+ and Cl-
Ca2+ reabsorption under PTH control
Thiazide diuretics
What is resorbed in the cortical collecting duct?
Na+ reabsorption (2-5%) coupled to K+ and H+ secretion
What is resorbed in the medullary collecting duct?qq
Water resorption under ADH control
True or false?
The nephron primarily regulates acid base through the secretion of bicarbonate and the resorption of H+
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
At what age to children achieve an adult GFR (approx 120 ml/min)?
2 years
Which of the following is the most precise way of calculating GFR?
a. inulin clearance study
b. DTPA
c. EDTA
d. Schwartz method
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
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 = d, normal C3
What proportion of children with IgA nephropathy experience ESRD?
20-30%, takes till 15-20 years from disease onset
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
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%)
Which is the most common mode of inheritance for Alport’s disease?
X-linked
COLA5 (alpha chain of type 4 collagen)
What is the most common presenting feature of Alport’s disease?
All patients have microscopic haematuria
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
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.
What is the benefit of treating patient’s with APSGN with pencillin?
Does not reduce risk/severity of GN
Prevents spread of nephritogenic strain
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
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
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)
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
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
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
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
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
Describe the features of Deny’s drash syndrome
Wilm’s tumour (90%)
Infant onset SRNS
Ambiguous genitalia
What is nephrotic range proteinuria?
Urine albumin creatinine ration >200 mg/mmol
What are the indication for biopsy in nephrotic syndrome?
Failure to respond to steroids
Age <1 or >12
Gross haematuria
Hypertension
Renal failure
What are the histopathological findings of minimal change disease?
Podocyte foot process effacement on EM
Will appear normal on light microscopy
What are the histological findings on FSGS?
LM = Focal sclerotic lesions
IF = stain IgM and C3 positive
EM - foot process effacement
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
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
What disease is associated with mutations in the NPHS1 gene?
Finnish type congenital nephrotic syndrome
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
. 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
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
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
what are the causes for increased ion gap metabolic acidosis?
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
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
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
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
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
patient with hyponatraemia. Serum osmolality is high or normal. What is suggested?
Factitious result. Hyperglycaemia, hyperlipidaemia, hypoproteinaemia
How long does microscopic haematuria persist after acute post streptococcal glomerulonephritis?
2 years
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
How is remission defined in nephrotic syndrome?
Dipstick negative for protein for 3 days or UPCR <22
Define frequency relapsing nephrotic syndrome
=2 relapses after Tx first 6 months or >/= 3 relapses in any given 12 months
what is the most common form of inheritance for Alport’s nephritis?
X-linked
COL4A4 (alpha collagen 5)
Boys more severely affected
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
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
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
