Renal

Question 1

Calculate Anion gap

Answer 1

NA+K - HC03+Cl

Question 2

ddx for NAGMA metabolic acidosis

Answer 2

1. Renal tubular acidosis (RTA) 2. Excessive HCO3 loss from GIT

Question 3

What is reabsorbed in the proximal tubule?

Answer 3

Glucose, amino acids, protein, vitamins, lactate, urea, uric acid, Na, K, Ca, Mg, , HC03, H20

not Cl

Question 4

What disorders cause Fanconi’s syndrome?

hint) there are three causes and only 2 are disorders

Answer 4

Inherited tubular disorders : cystinosis, Dents, Lowes
Metabolic disorders: wilsons, tyrosinaemia, hereditary fructose intolerance, galactosemia, type 1 glycogen storage disease,
drugs: aminoglycosides, valproate, cisplatin, ifosfamide
heavy metal toxicity

Question 5

What is Fanconi’s syndrome?

Answer 5

Generalised impairment of procimal tubule function.
Bicarbonate loss (Type 2 RTA)
Glycosuria
Hypophosphatemia
aminoaciduria
LMW proteinuria

Question 6

What are the types of RTA?

Answer 6

Type 1: distal RTA (impaired secretion of H+ in distal nephron)
Type 2: proximal RTA
Type 4: Hyperaldosteronism

Question 7

describe what happens in distal RTA

Answer 7

Distal (type 1) renal tubular acidosis (RTA) is characterized by impaired hydrogen ion secretion in the distal nephron, which reduces the kidney’s ability to excrete the daily acid load (50 to 100 mEq on a typical Western diet). This results in progressive hydrogen ion retention and a normal anion gap (or hyperchloremic) metabolic acidosis. If untreated, the plasma bicarbonate concentration can fall below 10 mEq/L.

Inability to excrete daily acid load
Progressive loss of buffer
Serum HCO3- < 10mmol/L
UpH >5.6
Hypokalaemia and sodium wasting
Hypercalciuria with risk of stones and nephrocalcinosis
Positive urinary anion gap (Na + K - Cl)

Question 8

Describe what happens in proximal RTA

Answer 8

RTA is caused by defects that reduce the capacity to reclaim filtered bicarbonate in the proximal tubule, there are 3 processes by which bicarbonate is reclaimed by the body. Abnormalities of one or more of the multiple proximal tubule transporters, pumps, or enzymes can impair sodium bicarbonate reabsorption and cause the bicarbonate wasting found in proximal RTA

Distal reabsorption modifies HCO3- loss Serum HCO3- usually 12-20mmol/L Bicarb wasting only occurs when plasma HCO3- is > renal threshold.

HCO3- infusion causes alkaline urine (pH>7.5)

Question 9

Describe what happens in type 4 Renal Tubular acidosis

Answer 9

reduced aldosterone effect (aldosterone maintains proper water balance by enhancing Na+ reabsorption and K+ secretion from extracellular fluid of the cells in kidney tubules.)

plasma bicarb >17mmol/L, urine pH <5.3, hyperkalemia, normal urinary calcium

Question 10

describe the 3 clin presentations of Bartter’s Syndrome

what diuretic (chronic ingestion) does this mimic?

Answer 10

Hypokalaemia, hypochloraemia, metabolic alkalosis
normotensive, hyperreninaemia
Increased urinary excretion of K, Cl and Na
UrinaryCl>10mmol/L
Hypercalciuria

Polyuria, polydipsia, vomiting, constipation, salt craving,
tendency to dehydration, FTT Fatigue, weakness and cramps Developmental delay Nephrocalcinosis

various genetic defects that cause Bartter syndrome directly or indirectly reduce the activity of one of several electrolyte transporters in the thick ascending limb.

Loop diuretic

Question 11

describe the pathophysiology of Bartter’s syndrome

Answer 11

Hereditary tubulopathy (group of) Can be considered as impaired Na+ and Cl- reabsorption in thick ascending limb (TAL) of Loop of Henle (LoH)
◦ Similar to action of frusemide
Increased K+ secretion distally
Decreased Ca++ reabsorption in LoH (coupled to Na-K-2Cl)

Question 12

Bartter’s: Differential Diagnosis?

Answer 12

Diuretic use (no increase in urinary PGE2 and no improvement with indomethacin). 
Laxative abuse, vomiting or bulimia (extra renal states of chloride depletion)-exclude by measuring urinary chloride. 
Mineralocorticoid excess (hypertension). 
Mitochondrial cytopathies with proximal tubular dysfunction (Kearns Sayre and Fanconi Syndrome can both mimic Bartter in infancy).

Question 13

Gitelman’s Syndrome; describe the major features and genetics

Answer 13

Hypokalaemia & hypomagnesaemia
Transient episodes of weakness and tetany
May have alkalosis
Urinary calcium low
Autosomal recessive ◦ NCCT gene (SLC12A3)
Diminished NaCl transport in distal CT
Like chronic thiazide use
Treat with magnesium

Question 14

describe the features of Diabetes insipidus

Answer 14

Diagnosis
◦ Polyuria in a dehydrated child + hypernatraemia
◦ Normal maximal urinary osmolality 800-1200 mmol/l decreased to 350-600 mmol/l.
◦ Lack of response to DDAVP distinguishes from central DI

Question 15

treatment of DI

Answer 15

Treatment
◦ Water
◦ Thiazides + amiloride (or indomethacin)
◦ Growth failure & developmental delay are both less likely with early treatment

Question 16

Where is sodium maximally reabsorbed in the kidney

Answer 16

1. Proximal tubule 60% (reg. by angiotensin)
2. Thick Ascending limb of LoH 30% (reg. by aldosterone)
3. Distal Convoluted tubule 5-8% (reg. by aldosterone)
4. Collecting Duct 2% (reg. by aldosterone)

Question 17

Define nephritis

Answer 17

Acute nephritic syndrome, characterized by red to brown urine, proteinuria (which can reach the nephrotic range), edema, hypertension, and an elevation in serum creatinine, which demonstrates inflammation In contrast to the protein losing Nephrosis. Often only C3 will be decreased as the

Question 18

Ddx for Nephritis and major defining fx?

Answer 18

1. C3 glomerulopathy (hematuria, hypertension, proteinuria, and hypocomplementemia, which may follow an upper respiratory infection in some patients. However, patients with C3 glomerulopathy continue to have persistent urinary abnormalities and hypocomplementemia beyond four to six week)
2. IgA nephropathy − Patients with IgA nephropathy often present after an upper respiratory infection, similar to the presentation of patients with PSGN. Potential distinguishing features from PSGN include a shorter time between the antecedent illness and hematuria (less than 5 versus more than 10 days in PSGN) and a history of prior episodes of gross hematuria since recurrence is rare in PSGN.
3. Secondary causes of glomerulonephritis − Lupus nephritis and IgA vasculitis (IgAV; Henoch-Schönlein purpura [HSP]) nephritis share similar features to PSGN. However, extrarenal manifestations of the underlying systemic diseases and laboratory testing should differentiate them from PSGN.

Question 19

Which pathway of the complement cascade is activated in PSGN, Atypical hemolytic uremic syndrome, C3 glomerulopathy

Answer 19

these glomerular diseases share uncontrolled activation of the alternative pathway as the defining pathophysiology

Question 20

what is the difference between osmolarity and osmololality

Answer 20

osmolarity is the molar concentration of solute particles per litre of solution, whereas osmolality is the molar concentration of solute particles per kg of solvent (water) (1 mole of solute for how much water?)
Normal body fluids osmolality: 285mOsmol/kg H20, urine osmolality may vary between 60 and 1400mOsmol/kg H20

Question 21

What cells respond to vasopressin and where are they in the nephron?

Answer 21

Principle (p) cells in the distal tubule respond to ADH
intercalated I cells that contain lots of mitochondria and secrete hydrogen ions

Question 22

Renin: where is it produced and what does it do?

Answer 22

Produced by the kidney, renin acts on angiotensin I, which is converted to angiotensin II, which is a potent vasoconstrictor affecitng blood pressure, tubular absorption of Na+, and aldosterone secretion from the adrenal glands. Renin release is stimulated by sympathetic filtration of the granular cells or a decrease in filtrate (Na+) concentration. The latter can occur following a fall in plasma volume, vasodilation of the afferent arterioles and renal ischaemia.

Question 23

Describe the pathway of Vitamin D

Answer 23

1. steroid hormone produced in food and synthesised in the skin in the presence of sunlight.
2. hydroxylated in the proximal tubules
3. regulated by PTH, phosphate and negative feedback. Active Vit D is essential for the mineralisation of bone, and promotes absorption of calcium ions and phosphate from the gut.

Question 24

What can pass through the glomerulus?

Answer 24

anything under the molecular weight of 70kDa (glucose, amino acids, Na, K, urea), and must be positively charged - due to the anions on the glomerular surface. protein bound molecules evven if positively charged cannot pass through.

Question 25

what are the main mechanisms that govern glomerular filtration?

Answer 25

1. tubuloglomerular feedback: responding to a change in tubular fluid flow rate 2. Myogenic mechanism: this responds to changes in arterial pressure

Question 26

Where is water mostly rebasorbed?

Answer 26

70% of water is reabsorbed in the proximal tubule - driven by a transtubular osmotic gradient, created by osmosis through the basement membrane into the peritubular capillary. this movement is also driven by the high oncotic pressure in the peritubular capillary.

Question 27

Where and how is chloride reabsorbed?

Answer 27

over 60% of chloride is reabsorbed in the middle and late tubule. chloride ions enter the cells by passive reabsorption, however intercellular potential prevents the entry into cells in the early part of the proximal tubule. the reabsorption of glucose, amino acids, and HC03 with Na+ in the initial part of the proximal tubule creates a filtrate that is concentrated with Cl-. This produces a diffusion gradient which allows movement of the ions into the intercellular space.

Question 28

reabsorption of glucose?

Answer 28

normal plasma glucose is 2.5-5.5mmol/L. usually 0.2-0.5 mmol of glucose is filtered every minute. and increase in the plasma glucose concentration results in a proportional amounf of glucose filtered. Virtually all filtered glucose is reabsorbed in the proximal tubule, unless the amount of filtered glucose exceeds the absorptive capacity of the cells.

Question 29

definition of an AKI?

Answer 29

stage 1: seru creatinine 1.5-1.9 above baseline; \<0.5mL/kg/hour urine for 6-12 hours. 2. 2.0-2.9 x baseline ; \<0.5mL/Kg/hr for \>12 hours Stage 3 serum creatinine 3 x baseline or decrease in egfr to \<35mL/Min/1.732m2 or initialtion of renal replacement therapy; \<3.0mL/Kg or anuria for \>12 hours

Question 30

What are the indications for RRT (renal replacement therapy)?

Answer 30

In children, the indications to initiate maintenance dialysis are in many ways similar to those in adults and consist of a combination of clinical (eg, uncontrolled hypertension, edema, and inability to provide adequate nutrition) and biochemical (eg, hyperkalemia, hyperphosphatemia, and acidosis) characteristics; AKI ◦ Volume overload not responsive to diuretics ◦ Hyperkalaemia and oliguria ◦ Maximise nutrition in oliguria ◦ Metabolic acidosis not responsive to other therapy ◦ Uraemic encephalopathy or pericarditis ◦ Tumor lysis syndrome ◦ Severe organic acidaemia or hyperammonaemia ◦ Specific toxins starting dialysis when eGFR is 10 to 15 mL/min/1.73 m2

Question 31

aetiology of AKI?

Answer 31

Prerenal: volume depletion (haemorrhage, GIT losses, DI, salt wasting); Redristibution: sepsis, nephrotic syndrome; capillary leak; inadequate effectiv volume (hepatorenal, CCF) Intrinsic Acute tubular necrosis (evolved from pre rena, drugs and toxins) Interstitial nephritis (drugs, idiopathic), glomerulonephritis vascular (HUS, renal artery or vein thrombosis, cortical necrosis) Obstruction hydronephrosis, myoglobinuria, lumour lysis

Question 32

What is the aetiology of acute tubular necrosis?

Answer 32

decreased renal perfusion with decreased gfr, resulting in loss of tubular function. Urine osmolality \<350mosm/kg), urinary sodium \>40mmol/L FeNa (functional excretion of sodium) \>2% (should be less than 1%)

Question 33

What are the three diagnostics criteria for HUS?

Answer 33

1. Microangiopathic haemolytic anaemia 2. Thrombocytopaenia 3. Acute nephropathy Extrarenal manifestations: GIT necrosis, Brain infarction, cerebral oedema, prancreatic necrosis, myocardial.

Question 34

Long term complications of HUS?

Answer 34

30-50% D+ (post diarrhoeal) have hypertension or renal abnormalities

Question 35

what is the aetiology and pathophysiology of HUS

Answer 35

1. post diarrhoea (90%) (verocytotoxin prodicing E coli - 0157:H7; 0111:H7) oliguria 4-7 days after 2. other infections, drugs, bone marrow, SLE, antiphospholipid syndrome, inherited defects in compliment proteins Genetic forms: low levels of C3; mutations in gene encoding factor H (negative regulator of C3) and other complement regulatory proteins.

Question 36

Treatment for atypical HUS?

Answer 36

Dialysis genetic forms: replace factor H with FFP/cryoprecipitate evolving role of eculizumab

Question 37

Most common atetiology for End Stage Kidney Disese

Answer 37

Glomerulonephritis (30%) FSGS, reflux nephropathy (10-20%), Hypoplasia/dysplasia (15%), Posteror urethral valves (7-10%), nephronopthisis, HUS (3%), familial glomerulonephritis, cystinosis. AR polycystic kidney disease, other 15%

Question 38

FSGS

Answer 38

FSGS is characterized by the presence of sclerosis in parts (segmental) of at least one glomerulus (focal) in the entire kidney biopsy specimen, when examined by light microscopy (LM), immunofluorescence (IF), or electron microscopy (EM). histologic lesion, rather than a specific disease entity, that is commonly found to underlie the nephrotic syndrome in adults and children. In primary FSGS, a putative circulating factor that is toxic to the podocyte causes generalized podocyte dysfunction manifested by widespread foot process effacement. Primary FSGS is often responsive to immunosuppressive therapy, including glucocorticoids, cyclosporine, and other immunosuppressive agents. By contrast, immunosuppression is not indicated in secondary FSGS.

Question 39

Reflux nephropathy

Answer 39

We believe the latter and will present convincing evidence supported by large scale prospective randomized controlled trials that VUR is not the ogre it was thought to be and is not important to find following a UTI (with some exceptions)

Question 40

nephronopthisis

Answer 40

Patients with NPHP have gene mutations that encode components of the ciliary apparatus. Although mutations in NPHP1 gene account for 20 percent of cases, at least 20 different genes have been associated with NPHP. All the genes encode proteins that are localized to the primary cilia, basal bodies, and centrosomes. These gene defects result in the characteristic findings of NPHP: - Autosomal recessive inheritance - Impaired urinary concentrating ability and sodium reabsorption - Bland urinalysis (absence of proteinuria, hematuria and cellular elements) - Chronic tubulointerstitial nephritis and progression to end-stage kidney disease (ESKD) generally before the age of 20 years

Question 41

Nephronopthisis clinical picture?

Answer 41

Nephronophthisis (NPHP) is a clinical condition caused by a group of autosomal recessive cystic kidney disorders NPHP is characterized by the insidious onset of end-stage kidney disease (ESKD). Extrarenal manifestations are present in 20 percent of patients, including retinitis pigmentosa, hepatic fibrosis, and skeletal defects

Question 42

What syndromes are associated with renal dysplasia?

Answer 42

renal hypodysplasia is associated with mutations in genes expressed during kidney development, including EYA1 and SIX1 (branchio-oto-renal syndrome), FRAS1 (Fraser syndrome), PAX2 (renal-coloboma syndrome), SALL1 (Townes-Brocks syndrome), TCF2 (renal cysts and diabetes mellitus), TRAP1 (VACTERL syndrome) and DSTYK (renal hypodysplasia, ureteropelvic junction obstructions, and vesicoureteral reflux) [13,26-28]. Mutations in the PBX homeobox 1 gene (PBX1), which is involved in renal development, were detected by targeted exome sequencing in 5 of 204 unrelated patients with CAKUT

Question 43

What are the major mutations associated with nephronopthisis?

Answer 43

Juvenile NPHP is associated with mutations in all the NPHP genes except NPHP2, including NPHP1, the most commonly affected gene. ●Mutations in NPHP2 and NPHP3 result in infantile and adolescent NPHP, respectively [17,25]. ●Mutations in NPHP5 are associated with retinitis pigmentosa (also referred to as tapetoretinal degeneration) and the Senior-Loken syndrome.Mutations in NPHP6 and NPHP8 are associated with retinal degeneration and cerebellar vermis aplasia in the Joubert syndrome or Meckel-Gruber syndrome.

Question 44

What are the major mutations associated with nephronopthisis?

Answer 44

- Juvenile NPHP is associated with mutations in all the NPHP genes except NPHP2, including NPHP1, the most commonly affected gene. - Mutations in NPHP2 and NPHP3 result in infantile and adolescent NPHP, respectively [17,25]. - Mutations in NPHP5 are associated with retinitis pigmentosa (also referred to as tapetoretinal degeneration) and the Senior-Loken syndrome.Mutations in NPHP6 and NPHP8 are associated with retinal degeneration and cerebellar vermis aplasia in the Joubert syndrome or Meckel-Gruber syndrome. infantile is the worst, and leads to CKF in the first year.

Question 45

posterior urethral valves

Answer 45

Posterior urethral valves (PUV) are obstructing membranous folds within the lumen of the posterior urethra that are the most common etiology of urinary tract obstruction in the newborn male. obstructing persistent urogenital membrane. bilateral hydronephrosis, dilated bladder, and a dilated posterior urethra (keyhole sign) in a male fetus is suggestive of PUV. Associated renal dysplasia is often seen in patients with PUV.

Question 46

ddx for nephropthisis?

Answer 46

The presence of the associated extrarenal findings (eg, retinitis pigmentosa) differentiates NPHP from the following chronic kidney disorders that present with a "bland" urine sediment (eg, no evidence of hematuria, cellular elements, or absence of proteinuria or mild tubular proteinuria) - Obstructive uropathy - Genetic ciliopathies resulting in cyst formation in children include early onset autosomal dominant polycystic kidney disease

Question 47

How and where is phosphate absorbed?

Answer 47

The amount of phosphate filtered is proportional to the amount of phosphate in the plasma. any increase in plasma phosphate \>1.2mmol/L leads to an increase in plasma filtered and excreted. reabsoption of phosphate occurs with Na+ ions (two Na+ for every Po) in the apical membrane of the tubular cells. A fall in GFR will result in an increase plasma phosphate concentration. Phosphate is an important urinary H+ buffer, its excretion is infulenced by - parathyroid hormone (increases), Vit D (Decreases excretion), Acidosis (increases excretion), glucocorticoids (increases excretion)

Question 48

What are the general principles of dialysis?

Answer 48

diffusion; movement of a solute down a concentration gradient ultrafiltration: when water crosses a semipermeable membrane driven by either hydrostatic or osmotic forse convection: movement of solutes with a fluid flux (ultrafiltration) Usually use dextrose as osmotic agent Can alter ◦ Concentration of dextrose (1.5%, 2.5% or 4.25%) & electrolytes ◦ Volume ◦ Dwell time, number of exchanges and frequency of exchanges Continuous cycling PD: automated exchanges, usually given at night Complications ◦ Peritonitis ◦ Catheter blockage, leak ◦ Membrane failure ◦ Electrolyte disturbance ◦ Hypotension

Question 49

What are the immunosuppresives used for kidney transplant?

Answer 49

triple therapy: Corticosteroids, calcineurin inhibitor (Tacrolimus or cylosporin), antimetabolies (mycophenylate or azathioprine) complicaions of immunosuppression: Infection ◦ CMV ◦ EBV ◦ post transplant lymphoproliferative disorder (PTLD) ◦ BKV nephropathy ◦ Pneumocystis jiroveci Diabetes, hypertension, growth, bones Nephrotoxicity Malignancy

Question 50

What are the prophyactic anti infectives used after kidney transplant and how long for

Answer 50

Valganciclovir: CMV Co-trimoxazole: PJP Usually continued for first 3-6months post transplant

Question 51

what is the main cause of oligohydramnios and why?

Answer 51

Fetal urine the main source of amniotic fluid after 16 – 18 weeks gestation Causes of oligohydramnios ◦ Bilateral kidney anomaly (hypoplasia, dysplasia, autosomal recessive polycystic kidneys) ◦ Bilateral obstruction ◦ Severe IUGR ◦ Spontaneous rupture of membranes

Question 52

What are the main causes of antenatal hydronephrosis?

Answer 52

Obstruction ◦ Pelvi-ureteric junction ◦ Vesico-ureteric junction (would expect to see dilated ureter) ◦ Posterior urethral valves (bilateral hydronephrosis in a male)

Question 53

What does a DMSA scan look for?

Answer 53

scarring and dysplasia - demonstrates discrete and generalised defects and differential function. ## Footnote - ‘Staticscan’ - DMSA is filtered by glomeruli and reabsorbed by prox. tubules - Identifies functioning renal cortical tissue - Uptake reduces in inflammation, scarring, dysplasia & CKD - Used to confirm dysplasia/scarring or APN - Timing is critical in interpretation - Can also Dx ectopic and duplex kidneys (not often needed)

Question 54

What is a nuclear medicine scan (MAG3/DTPA) used for?

Answer 54

* ‘Dynamic scan’ * Used to assess blood flow/perfusion and to localise obstruction * Nephrogram phase can show scarring/dysplasia (less sensitive than DMSA) and overall uptake (perfusion) * Washout phase (+/\_ furosemide) shows obstruction (provided OK uptake) e.g. PUJO

Question 55

What are the extrarenal associations with Bartter's syndrome what are the genes responsible?

Answer 55

SLC12A1/KCNJ1 romk senosineural hearing loss

Question 56

What is polycystic kidney disease and what are the genetics associated?

Answer 56

In affected individuals with ADPKD, renal involvement is characterized by cystic dilatations in all parts of the nephron, including Bowman's space and all tubular segments Autosomal Dominant; PKD1 and 2 Neonatal : oligohydramnios, massively enlarged kidneys, respiratory distress, and impaired kidney function) to those seen in neonates with autosomal recessive polycystic kidney disease

Question 57

What is cresenteric glormerulonephritis?

Answer 57

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome manifested by features of glomerular disease in the urinalysis and by progressive loss of kidney function over a comparatively short period of time (days, weeks, or a few months). It is most commonly characterized morphologically by extensive crescent formation (extracapillary proliferation in Bowman's space)

Question 58

ddx for asymptomatic haematuria?

Answer 58

Primary: mesangial IgA glomerulonephritis exercise induced myoglobinuria secondary: HSP/SLE/bacterial endocarditis

Question 59

ddx for asymptomatic proteinuria

Answer 59

primary glomerular: mesangial capillary GN, focal segmental glomerulosclerosis, shunt nephritis, renal scarring secondary: HSP/SLE/bacterial endocarditis, polyarteritis nodosa, hypertension, pregnancy

Question 60

Ddx for acute nephritic syndrome?

Answer 60

PSGN, non strep GN, rapidly progressive GN, focal proliferative GN, mesangial IgA GN secondary: SLE/microscopic polyangiitis, wegner's granulomatosis

Question 61

ddx for nephrotic syndrome

Answer 61

primary glomerular: minimal change disease, membranous glomerular nephropathy, membranoproliferative GN, focal segmental glomerulosclerosis secondary: HSP, SLE, tumour, amyloid, DM, drugs (penicillinane, gold, heroin), bacterial endocarditis, congenital nephrotic syndrome

Question 62

What is the fractionl excretion of Na?

Answer 62

amount excreted/amount filtered fNa+= UNa x serum creatinine/ serum Na x Urine creatinine

Question 63

ddx for Hypochloremic Hypokalemic Metabolic Alkalosis with Hypotension

Answer 63

* Surreptitious vomiting * Diuretic abuse (remote) * Cl-losing diarrheaor Laxative abuse (often met acidosis) \*look at urinary chloride High urine Cl-think Bartters/Gittelman

Question 64

What are the transporters in the proximal tubule cell walls?

Answer 64

1. NA/K ATPase (2k into tubule cell, 3Na into blood) 2. NBCe1A (NA in 3HC03 salvaged into blood) 3. H/ATPase (H+ into tubule) 4. NHE3 (Na into tubule CELL, H+ back out into tubule) 5. AQP1 (water into tubule cell)

Question 65

What are the transporters in the LoH tubule cell walls?

Answer 65

ROMK : k+ into tubular lumen (recycled) NA/K/2Cl (NKCC2) -all these in to cell FROM LUMEN, creating hypertonic medullary concentratin gradient Ca +Mg = passive Chloride channel (Clc-Kb) NA/KATPase \*all but the active transport are messed up in Bartter syndrome

Question 66

What are the transporters in the distal tubule walls?

Answer 66

NaCl co transporter (NCC). (both in from tubulular lumen into cell) Ca2+ VitD/PTH dependent (Na into cell, Ca into blood) CaBP - Barttin Chloride Channel (ClC-Kb) (chloride into blood at the end of the ride) Na/KATPase (K into cell, Na into blood) the NACl cotransporter is messed up in Gitelmans (Hypokalemic metabolic alkalosis (salt wasting, distal H+K+ secretion, Hypomagnesemic, hypocalciuric, Present with mm cramps/tetany)

Question 67

what are the transporters in the collecting Tubule cell walls?

Answer 67

ENaC: Na+ in by ENaC ROMK: K secretion Na/KATPase aquaporins Lumen electroneg ALDOSTERONE * Combines with MineralocorticoidReceptor * increase ENaC * increase Na/K/ATPase * Ultimately increase ECF/BP

Question 68

What is CCT –Liddles(“~HYPERaldosteronism”)

Answer 68

Liddles= “EnacON” * HTN * Suppressed Renin & Aldo * Hypokalemia * Metabolic Alkalosis * AD * =ALDO Resistance * ENaC mutation “OFF” –Rare AR * Aldosterone RResistance AD (Milder Sx) * Na+ wasting * Hypovalemia * Hyperkalemia * Inc Aldosterone Other stimulants AldoR * xsCortisol * 11-beta-HSD2 mutation(AME) * xsACTH•some CAH * Liquorice (inhib11-beta-HSD2)

Question 69

what are the intercalated cells in the collecting tubule, what kinds are there and what do each do?

Answer 69

* No Na/K/ATPase * Cation secretion to balance Na+ resorption in principal cells H20 dissociates •H+ ATPase * H+ secretion•combine with titratable buffers in lumen * HCO3-creation & absorption into blood * K+ reabsorption * Increased H+ATPase in hypokalemia can perpetuate met alkalosis Type A –acid secreting/ bicarb reclaiming (10%) Type B –secrete bicarb / needs distal chloride delivery“contraction alkalosis”

Question 70

what is contraction alkalosis?

Answer 70

Contraction alkalosis refers to the increase in blood pH that occurs as a result of fluid losses (volume contraction). The change in pH is especially pronounced with acidic fluid losses caused by problems like vomiting. the cells in the collecting tubule (AE1) Type B –secrete bicarb / needs distal chloride delivery“contraction alkalosis” so if there is no chloride due to vomiting, you end up keeping the bicarb in the urine

Question 72

How is water regulated in the collecting duct?

Answer 72

Aquaporins * Renal free water excretion * Aquaporin1 –constitutively active in all segments•Aquaporin2 – * Dilute urine enters inner medullary collecting duct * Rapid water permeability in presence of Vasopressin * Net water absorption driven by osmotic gradient

Question 73

How do you differentiate Nephrogenic DI from central DI

Answer 73

water deprivation test when dehydrated give DDAVP (should open aquaporins in the collecting duct and make the urine more concentrated) if no reponse, nephrogenic. if urine becomes concentrated it is central. U Osm350-600mmol/L - normal is above 500 (500-850) nephro: •CKD/Nephronophthisis•Lithium•Hypercalcemia/hypercalciuria•Post-obstruction•Bartters•Sickle cell anemia•Hypokalemia

Question 74

how do you differentiate IgA nephropathy from PSGN?

Answer 74

Normal serum levels of C3 in IgA nephropathy help to distinguish this disorder from post- streptococcal glomerulonephritis. Morphologic studies and a depression in the serum complement (C3) level provide strong evidence that ASPGN is mediated by immune complexes. The serum C3 level is significantly reduced in \>90% of patients in the acute phase, and returns to normal 6-8 wk after onset.

Question 75

complications of IgA nephropathy?

Answer 75

CKD years down the track prompting good follow-up ## Footnote A more severe prognosis is correlated with histologic evidence of diffuse mesangial proliferation, extensive glo- merular crescents, glomerulosclerosis, and diffuse tubulointerstitial changes, including inflammation and fibrosis.

Question 77

Treatment of IGA nephropathy

Answer 77

The primary treatment of IgA nephropathy is appropriate blood pressure control and management of significant proteinuria. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists are effective in reducing proteinuria and retarding the rate of disease progression when used individually or in combination

Question 78

What is Alport Syndrome?

Answer 78

AS, or hereditary nephritis, is a genetically heterogeneous disease caused by mutations in the genes coding for type IV collagen, a major component of basement membranes.

Question 79

What is the pathogenesis of Alport Syndrome?

Answer 79

Later, the glomeruli may develop mesan- gial 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.

Question 80

progressive symptoms of Alport Syndrome? treatment of

Answer 80

Haematuria, progressive proteinuria, progressive bilateral sensorineural hearing loss. anterior lenticonus (extrusion of the central portion of the lens into the anterior chamber), macular flecks, and corneal erosions. No specific treatment, although ACE inhibitors and AR2B, can help. ESKD can be treated with dialysis and kidney replacement.

Question 81

Acute glomerular nephritis with low c3

Answer 81

↓↓Serum complement (C3, CH 50) Systemic diseases * Lupus nephritis (focal 75%, diffuse 90%) * Subacute bacterial endocarditis (90%) * Shunt nephritis (90%) * Essential mixed cryoglobulinemia (85%) * Visceral abscess Renal diseases * Acute postinfectious GN (􏰀90%) * Membranoproliferative GN Type I (50–80%

Question 82

Acute glomerulonephritis with normal complement?

Answer 82

Normal serum complement Systemic diseases * Polyarteritis nodosa * Hypersensitivity vasculitis * Granulomatosis with polyangiitis • Henoch-Schönlein purpura * Goodpasture syndrome Renal diseases * IgA nephropathy * Idiopathic rapidly progressive (crescentic) GN Type I (anti-GBM disease) Type II (immune complex CGN) Type III (pauciimmune CGN) Postinfectious GN(nonstreptococcal)

Question 83

post gomerulonephritis in which complement fails to return to normal in 6-8 weeks?

Answer 83

**Lupus nephritis (anti–nuclear antibodies, anti–double-stranded DNA antibody)** Essential mixed cryoglobulinemia (cryoglobulin, hepatitis C virus) Shunt nephritis (history, clinical symptoms) Visceral abscess (blood culture) **Membranoproliferative GN (C3NF)** Bacterial endocarditis Post infectious GN (non streptococcal)

Question 84

What are the most common etiologies for Membranous glomerulonephritis?

Answer 84

The most common etiologies of secondary MN are sys- temic lupus erythematosus or chronic infections. Among the latter, chronic hepatitis B infection and congenital syphilis. Primary - Glomeruli have diffuse thickening of the glomerular basement mem- brane (GBM), without significant cell proliferative changes. Immuno- fluorescence and electron microscopy typically demonstrate granular deposits of immunoglobulin G and C3 located on the epithelial side of the GBM. The GBM thickening presumably results from the produc- tion of membrane-like material in response to deposition of immune complexes

Question 85

Pathogenesis for membranous glomerulonephritis? clinical presentation?

Answer 85

MN is believed to be caused by in situ immune complex formation. Therefore, antigens from the infectious agents or medications associ- ated with secondary MN directly contribute to the pathogenesis of the renal disease. circulating antibody to the antigen that is often found on podocytes, but the M-type phospholipase A2 receptor, present on normal podocytes. Most patients also have microscopic hematuria and only rarely present with gross hematuria. Approximately 20% of children have hypertension at presentation.

Question 86

Treatment for membranous glomerulonephritis?

Answer 86

immunosuppressive therapy with an extended course of **prednisone** can be effective in promoting complete resolution of symptoms. The addition of chlorambucil or **cyclophosphamide** appears to provide further benefit to those not responding to steroids alone. **Rituximab** has shown significant promise in adults and has been proposed by some as first line treatment but has yet to be studied in a randomized controlled trial in any age group.

Question 87

Membranoproliferative glomerulonephritis (MPGN), also known as mesangiocapillary glomerulonephritis, how is it classified?

Answer 87

Secondary forms of MPGN are most commonly associated with subacute and chronic infection, including hepatitides B and C, syphilis, subacute bacterial endocarditis, and infected shunts, especially ventriculoatrial shunts (shunt nephritis). MPGN can also be one of the glomerular lesions seen in lupus nephritis

Question 88

What types of membranoproliferative glomerulonephritis are there and what are thier fx?

Answer 88

**Type I MPGN** is most common. Glom- eruli have an accentuated lobular pattern from diffuse mesangial expansion, endocapillary proliferation, and an increase in mesangial cells and matrix. The glomerular capillary walls are thickened, often with splitting from interposition of the mesangium. Crescents, if present, indicate a poor prognosis. Immunofluorescence microscopy reveals C3 and lesser amounts of immunoglobulin in the mesangium and along the peripheral capillary walls in a lobular pattern. Far less common is type **II MPGN**, also called dense deposit disease, which has similar light microscopic findings as type I MPGN. Differentiation from type I disease is by immunofluorescence and electron microscopy. In type II disease, C3 immunofluorescence typi- cally is prominent, without concomitant immunoglobulin. By electron microscopy, the lamina densa in the glomerular basement membrane undergoes a very dense transformation, without evident immune complex–type deposits. **C3** glomerulonephritis (C3GN) is a related but separate diagnostic category. By light and electron microscopy C3GN usually has features indistinguishable from classical MPGN. Immunofluorescence studies distinguish between the two, with C3GN having only C3 deposition and MPGN having both C3 and immunoglobulin fluorescence.

Question 89

What is the pathogenesis of Type 1 membranoproliferative glomerulonephritis?

Answer 89

in Tyope 1: circulating immune complexes become trapped in the glomerular subendothelial space, which then causes injury, resulting in the characteristic proliferative response and mesangial expansion. Further evidence confirming this pathway to glomerular injury is the finding of complement activation through the classical pathway in as many as 50% of affected patients. in Type 2; it is not at all immune mediates C3 is mediated by C3 deposits

Question 90

Ddx for membranoproliferative glomerulonephritis?

Answer 90

Postinfectious glomerulone- phritis, far more common than MPGN, usually does not have nephrotic features but typically has hematuria, hypertension, renal insufficiency, and transiently low C3 complement, all features that may be seen with MPGN or C3GN. In contrast to MPGN and C3GN, where C3 levels usually remain persistently low, C3 returns to normal within 2 mo after onset of postinfectious glomerulonephritis

Question 91

pathogenesis of SLE nephritis?

Answer 91

rather than simply trapping the immune complexes, circulating immune complexes bind to the glomerular components

Question 92

classifiction of SLE nephritis?

Answer 92

I. Minimal mesangial LN No renal findings II. Mesangial proliferative LN Mild clinical renal disease; minimally active urinary sediment; mild to moderate proteinuria (never nephrotic) but may have active serology III. Focal proliferative LN \<50% glomeruli involved A. Active A/C. Active and chronic C. Chronic More active sediment changes; often active serology; increased proteinuria (approximately 25% nephrotic); hypertension may be present; some evolve into class IV pattern; active lesions require treatment, chronic do not IV. Diffuse proliferative LN (\>50% glomeruli involved); all may be with segmental or global involvement (S or G) A. Active A/C. Active and chronic C. Chronic Most severe renal involvement with active sediment, hypertension, heavy proteinuria (frequent nephrotic syndrome), often reduced glomerular filtration rate; serology very active. Active lesions require treatment V. Membranous LN glomerulonephritis Significant proteinuria (often nephrotic) with less active lupus serology VI. Advanced sclerosing LN More than 90% glomerulosclerosis; no treatment prevents renal failure

Question 93

Pathogenesis of HSP clinical manifestations

Answer 93

Henoch-Schönlein purpura (HSP) is the most common small vessel vasculitis in childhood. It is characterized by a purpuric rash and com- monly accompanied by arthritis and abdominal pain (see Chapter 167.1). Approximately 50% of patients with HSP develop renal mani- festations, which vary from asymptomatic microscopic hematuria to severe, progressive glomerulonephritis. The pathogenesis of HSP nephritis appears to be mediated by the deposition of polymeric immunoglobulin A (IgA) in glomeruli. The nephritis associated with HSP usually follows onset of the rash, often presenting weeks or even months after the initial presentation of the disease. Nephritis can be manifest at initial presentation, but only rarely before onset of the rash. Most patients have only mild renal manifestations, princi- pally isolated microscopic hematuria without significant proteinuria. Initial mild renal involvement can occasionally progress to more severe nephritis despite resolution of all other features of HSP

Question 94

what are the types of rapidly progressive glomerulonephritis?

Answer 94

PRIMARY Type I: Anti–glomerular basement membrane antibody disease, Goodpasture syndrome (with pulmonary disease) Type II: Immune complex mediated Type III: Pauciimmune (usually antineutrophil cytoplasmic antibody-positive) SECONDARY Membranoproliferative glomerulonephritis Immunoglobulin A nephropathy, Henoch-Schönlein purpura Poststreptococcal glomerulonephritis Systemic lupus erythematosus Polyarteritis nodosa, hypersensitivity angiitis

Question 95

what is the hallmark of rapidly progressing (cresenteric) GN?

Answer 95

The hallmark of CGN is the histopathologic finding of crescents in glomeruli. Crescent formation, through proliferation of parietal epithelial cells in Bowman’s space, may be the final pathway of any severe inflammatory glomerular injury.

Question 96

What are the major diagnostic feature of cresenteric (rapidly progressing GN)

Answer 96

The immunofluorescence findings, as well as the pattern of any deposits by electron microscopy can delineate the underlying glomerulopathy in CGN secondary to lupus, HSP nephri- tis, membranoproliferative glomerulonephritis, postinfectious GN, IgA nephropathy, or Goodpasture disease. Rare or absent findings by immunofluorescence and electron microscopy typify pauciimmune GN (Wegener disease and microscopic polyangiitis) and idiopathic crescentic GN.

Question 97

Presentation of rapidly progressing (cresenteric) GN

Answer 97

Most children present with acute **nephritis** (hematuria, some degree of renal insufficiency, and hypertension) and usually have concomitant proteinuria, often with **nephrotic** syndrome. Occasional patients present late in the course of disease with oliguric renal failure. Extra- renal manifestations, such as pulmonary involvement, joint symptoms, or skin lesions, can help lead to the diagnosis of the underlying sys- temic disease causing the CGN.

Question 98

prognosis and treatment of cresenteric/rapidly progressive GN?

Answer 98

Having a majority of fibrous crescents on a renal biopsy portends a poor prog- nosis, because the disease usually has progressed to irreversible injury. Although there are few controlled data, the consensus of most nephrol- ogists is that the combination of high-dose corticosteroids and cyclo- phosphamide may be effective in preventing progressive renal failure in patients with systemic lupus erythematosus, HSP nephritis, Wegener granulomatosis, and IgA nephropathy

Question 99

what is goodpasture disease?

Answer 99

Goodpasture disease is characterized by pulmonary hemorrhage and glomerulonephritis. The disease results from attack on these organs by antibodies directed against certain epitopes of type IV collagen, located within the alveolar basement membrane in the lung and glomerular basement membrane (GBM) in the kidney. The production of patho­ logic autoantibody against specific domains in type IV collagen is triggered by an acquired conformational change in α345NC1 hexa­ mers, central structural elements in type IV collagen. The resulting structural alteration reveals neoepitopes that become the target of the pathogenic Goodpasture autoantibody.

Question 100

what are the biomarkers for goodpastures?

Answer 100

In essentially all cases, serum anti­GBM antibody is present and complement C3 level is normal. Antineutrophilic cytoplasmic antibody levels can be found to be elevated along with the anti­GBM antibody; such patients doubly positive for these autoantibodies, who have severe disease at presenta­ tion, appear to have a more severe prognosis.

Question 101

What are the ddx and diagnosis of Goodpastures disease?

Answer 101

The diagnosis is made by a combination of the clinical presentation of pulmonary hemorrhage with acute glomerulonephritis, the presence of serum antibodies directed against GBM (anti–type IV collagen in GBM), and characteristic renal biopsy findings. Other diseases that can cause a pulmonary­renal syndrome need to be considered and include systemic lupus erythematosus, Henoch­Schönlein purpura, granulo­ matosis with polyangiitis, nephrotic syndrome–associated pulmonary embolism, and microscopic polyangiitis. These diseases are ruled out by the absence of other characteristic clinical features, kidney biopsy findings, and negative serologic studies for antibodies against nuclear (antinuclear antibody), DNA (anti­dsDNA), and neutrophil cytoplas­ mic components (antineutrophilic cytoplasmic antibody).

Question 102

What is involved with the supportive care of HUS?

Answer 102

Supportive care includes careful management of fluid and electrolytes, including prompt correction of volume deficit, control of hypertension, and early institution of dialysis if the patient becomes significantly oliguric or anuric, particularly with hyperkalemia. Early intravenous volume expansion before the onset of oligo anuria may be nephroprotective in diarrhea-associated HUS. Red cell transfusions are usually required as hemolysis can be brisk and recurrent until the active phase of the disease has resolved. In pneumococci-associated HUS, it is critical that any administered red cells be washed before transfusion to remove residual plasma, because endogenous IgM directed against the revealed T antigen can play a role in accelerating the pathogenesis of the disease. Prompt antobiotic treatment

Question 103

Ddx for bilateral flank masses and haematuria/dysuria

Answer 103

Renal Vein thrombosis: USS ## Footnote autosomal recessive polycystic kidney disease (ARPKD): ARPKD may be associated with oli- gohydramnios, pulmonary hypoplasia, respiratory distress, and spontaneous pneumothorax in the neonatal period. Nephronopthesis

Question 104

Nephronophthisis and associated syndromes?

Answer 104

**Nephronophthisis**, an autosomal recessive disorder with renal fibrosis, tubular atrophy, and cyst formation is a common cause of ESRD in children and adolescents. Associated external findings include retinal degeneration **(Senior-Loken** syndrome), cerebellar ataxia (**Joubert** syndrome), and hepatic fibrosis (**Boichis** disease). Symptoms include polyuria (salt wasting, poor con- centrating ability), failure to thrive, and anemia.

Question 105

list three causes of proteinuria

Answer 105

glomerular proteinuria, which occurs as a result of disruption of the glomerular capillary wall; tubular proteinuria, a tubular injury or dysfunction that leads to ineffective reabsorption of mostly low-molecular-weight proteins; and increased production of plasma proteins—in multiple myeloma, rhabdomyolysis, or hemolysis—which may cause the production or release of very large amounts of protein that are filtered at the glomerulus and overwhelm the absorptive capacity of the proximal tubule.

Question 106

What is Protein/creatinine measuring, what is expected and what is the significance is an abnormal

Answer 106

Urine protein-to-creatinine ratio measurement of an untimed (spot) urine specimen has largely replaced timed urine collection. In chil- dren, urine protein-to-creatinine ratios have been shown to signifi- cantly correlate with measurements of 24 hr urine protein and are useful to screen for proteinuria and to longitudinally monitor urine protein levels. This ratio is calculated by dividing the urine protein concentration (mg/dL) by the urine creatinine concentration (mg/dL) to provide a simple measure. It should be ideally performed on a first morning voided urine specimen to eliminate the possibility of orthostatic (pos- tural) proteinuria (see Chapter 525). A ratio of \<0.5 in children \<2 yr of age and \<0.2 in children \>2 yr of age suggests normal urinary protein excretion. A ratio greater than 2 suggests nephrotic-range proteinuria.

Question 107

nephrotic syndrome clin fx?

Answer 107

The triad of clinical findings associated with nephrotic syndrome arising from the large urinary losses of protein are hypoalbuminemia (≤2.5 g/dL), edema, and hyperlipidemia (cholesterol \>200 mg/dL).

Question 108

ddx for proteinuria?

Answer 108

1. idiopathic (FSGA/Membranous Nephropathy/minimal change) 2. secondary: Membranous Nephropathy (hepatitis, systemic lupus erythematosus [SLE] or malignancy) or toxins and drugs such as nonsteroidal antiinflammatory, gold, mercury, bismuth, silver, d -penicillamine, trimethadione, probenecid, and captopril. )

Question 109

Glomerular lesions associated with idiopathic nephrotic syndrome?

Answer 109

minimal change disease (the most common), focal segmental glomerulosclero- sis, membranoproliferative glomerulonephritis, C3 glomerulopathy, and membranous nephropath

Question 111

major complications of nephrotic syndrome?

Answer 111

Children with nephrotic syndrome are especially susceptible to **infections** such as cellulitis, spontaneous bacterial peritonitis, and bacteremia. This occurs as a result of many factors, particularly hypoglobulinemia as a result of the urinary losses of immunoglobulin (Ig) G. In addition, defects in the complement cascade from urinary loss of complement factors (predominantly C3 and C5), as well as alter- native pathway factors B and D, lead to impaired opsonization of microorganisms. Children with nephrotic syndrome are at signifi- cantly increased risk for infection with encapsulated bacteria and, in particular, pneumococcal disease. Spontaneous bacterial peritonitis presents with fever, abdominal pain, and peritoneal signs. Although Pneumococcus is the most frequent cause of peritonitis, Gram-negative bacteria also are associated with a significant number of cases. **Thrombus** the hypercoagulable state renders it likely **Hyperlipidaemia**

Question 112

ddx for idopathic nephrotic syndrome

Answer 112

MINIMAL CHANGE NEPHROTIC SYNDROME FOCAL SEGMENTAL GLOMERULOSCLEROSIS MEMBRANOUS NEPHROPATHY MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS Type I Type II

Question 113

nephrotic syndrome clin fx?

Answer 113

Children usually present with mild edema, which is initially noted around the eyes and in the lower extremities. Nephrotic syndrome can initially be misdiagnosed as an allergic disorder because of the perior- bital swelling that decreases throughout the day. With time, the edema becomes generalized, with the development of ascites, pleural effu- sions, and genital edema. Anorexia, irritability, abdominal pain, and diarrhea are common. Important features of minimal change idio- pathic nephrotic syndrome are the absence of hypertension and gross hematuria (the so-called nephritic features).