Renal

Question 1

POTTER sequence syndrome

Answer 1

1. Pulmonary hypoplasia
2. Oligohydramnios
3. Twisted face
4. Twisted skin
5. Extremity defects
6. Renal failure (in utero)

Question 2

• Plasma volume is measured by ….
• Extracellular volume measured by ….
• Osmolality = …. mOsm/kg H₂O
• GFR can be best estimated with ….
• RPF is best estimated with ….

Answer 2

• Plasma volume is measured by radiolabeled albumin
• Extracellular volume measured by inulin
• Osmolality = 285-295 mOsm/kg H₂O
• GFR can be best estimated with creatinine clearance
• RPF is best estimated with PAH clearance

Question 3

1. Filtered load =
2. Excretion rate =
3. Reabsorption =
4. Secretion =

Answer 3

1. Filtered load = GFR x P_x
2. Excretion rate = V x U_x
3. Reabsorption = filtered – excreted
4. Secretion = excreted – filtered

Question 4

• Afferent arteriole constriction
• Efferent arteriole constriction
• ↑ plasma protein concentration
• ↓ plasma protein concentration
• Constriction of ureter

Answer 4

• Afferent arteriole constriction
  
  • ↓ GFR, ↓ RPF, – FF
• Efferent arteriole constriction
  
  • ↑ GFR, ↓ RPF, ↑ FF
• ↑ plasma protein concentration
  
  • ↓ GFR, – RPF, ↓ FF
• ↓ plasma protein concentration
  
  • ↑ GFR, – RPF, ↑ FF
• Constriction of ureter
  
  • ↓ GFR, – RPF, ↓ FF

Question 5

• Where are amino acids reabsorbed?
• What is Hartnup’s disease?

Answer 5

• Amino acid clearance:
  
  • Na⁺-dependent transporter in PCT reabsorb amino acids
• Hartnup’s disease
  
  • Autosomal recessive
  • Deficiency of neutral amino acids (e.g. tryptophan) transporter in proximal renal tubular cells and on enterocytes ⇒
    
    • neutral aminoaciduria and ↓ absorption from gut
  • ↓ tryptophan for conversion to niacin ⇒ pellagra-like symptoms
  • Treatment: high protein diet + nicotinic acid

Question 6

Glucose clearance:

• Site of absorption:
• Threshold:
• What happens in pregnancy?

Answer 6

• Site of absorption:
  
  • At normal levels, completely reabsorbed in PCT by Na⁺/glucose co-transport
• Threshold:
  
  • ~200 mg/dL ⇒ glucosuria begins
  • ~375 mg/dL ⇒ all transporters are fully saturated (T_m)
• What happens in pregnancy?
  
  • normal pregnancy may decrease the ability of PCT to reabsorb glucose and amino acids ⇒
    
    • glucosuria and aminoaciduria

Question 7

Where do PTH and AT II act?

Answer 7

• PTH (early PCT) → inhibits Na⁺/PO₄^3- cotransport → PO₄^3- excretion
• PTH (early DCT) → ↑ Ca²⁺/Na⁺ exchange → Ca²⁺ reabsorption
• AT II (early PCT) → stimulates Na⁺/H⁺ exchange → ↑ Na, H₂O and HCO₃– reabsorption (permitting contraction alkalosis)

Question 8

When does urine become hypertonic?

Answer 8

Thin descending loop of Henle

• passively reabsorbs H₂O via medullary hypertonicity (impermeable to Na⁺)

Question 9

When does urine become the most dilute (hypotonic)?

Answer 9

Early DCT

Question 10

Where do aldosterone and ADH act?

Answer 10

Collecting tubule

• Aldosterone (acts on mineralocorticoid receptor) → mRNA → protein synthesis
  
  • In principal cells: ↑ apical K⁺ conductance, ↑ Na⁺/K⁺ pump, ↑ ENaC channels → lumen negativity → K⁺ loss
  • In α-intercalated cells: ↑ H⁺ ATPase activity → ↑ HCO₃^-/Cl^- exchanger activity
• ADH (acts on V₂ receptor) → insertion of aquaporin H₂O channels on apical side

Question 11

List the renal tubular defects

Answer 11

“The kidneys put out FABulous Glittering LiquidS”

1. FAnconi syndrome (affects PCT)
2. Bartter syndrome (affects thick ascending loop)
3. Gitelman syndrome (affects DCT)
4. Liddle syndrome (affects collecting tubule)
5. Syndrome of apparent mineralcorticoid excess

Question 12

Fanconi syndrome:

• Area affected:
• Associations:
• Causes:

Answer 12

• Area affected:
  
  • reasorptive defect of PCT
• Associations:
  
  • ↑ excretion of nearly all amino acids, glucose, HCO₃^- and PO₄^3-
  • May result in proximal renal tubular acidosis (metabolic acidosis w/ normal anion gap)
• Causes:
  
  • hereditary defects (Wilson disease, tyrosinemia, glycogen storage disease)
  • ischemia
  • multiple myeloma
  • nephrotoxins/drugs (expired tetracyclines, tenofovir)
  • Pb poisoning

Question 13

Bartter syndrome

• Area affected:
• Mode of inheritance:
• Results in ….

Answer 13

• Area affected:
  
  • reabsoprtive defect in thick ascending loop of Henle
  • Na+/K+/2Cl- cotransporter
• Mode of inheritance:
  
  • autosomal recessive
• Results in hypokalemia and metabolic alkalosis w/ hypercalciuria

Question 14

Gitelman syndrome

• Area affected:
• Mode of inheritance:
• Results in ….

Answer 14

• Area affected:
  
  • reabsorptive defect of NaCl in DCT
• Mode of inheritance:
  
  • autosomal recessive
  • less severe than Bartter syndrome
• Results in hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria

Question 15

Liddle syndrome

• Area affected:
• Mode of inheritance:
• Results in ….
• Treatment ⇒

Answer 15

• Area affected:
  
  • Gain of function mutation → ↑ Na+ reabsorption in collecting tubules (↑ activity of ENaC)
• Mode of inheritance:
  
  • autosomal dominant
• Results in HTN, hypokalemia, metabolic alkalosis, ↓ alsosterone
• Treatment ⇒ Amiloride

Question 16

Syndrome of apparent mineralocorticoid excess

• How is it acquired?
• Pathophysiology:
• What will be seen on labs?
• Results in ….

Answer 16

• How is it acquired?
  
  • Hereditary deficiency of 11β-hydroxysteroid dehydrogenase (converts cortisol ⇒ cortisone)
  • Can be acquired from glycyrrhetic acid (present in licorice) which blocks 11β-hydroxysteroid dehydrogenase activity
• Pathophysiology:
  
  • Excess cortisol → ↑ mineralocorticoid receptor activity
• Labs show low serum aldosterone levels
• Results in HTN, hypokalemia, metabolic alkalosis

Question 17

K⁺ shifts

• Causes of Hyperkalemia
• Causes of Hypokalemia

Answer 17

• Causes of Hyperkalemia (“DO LAβS”)
  
  • Digitalis (blocks Na⁺/K⁺ ATPase)
  • HyperOsmolarity
  • Lysis of cells (crush injury, rhabdomyolysis, cancer)
  • β-blockers
  • High blood Sugar
• Causes of Hypokalemia
  
  • Hypo-osmolarity
  • Alkalosis
  • β-agonists (↑ Na⁺/K⁺ ATPase)
  • Insulin (↑ Na⁺/K⁺ ATPase)
    
    • Insulin shifts K⁺ into cells

Question 18

Electrolyte disturbances: Low serum concentrations

• Na⁺
• K⁺
• Ca²⁺
• Mg²⁺
• PO₄^3-

Answer 18

• Na⁺
  
  • Nausea, malaise, stupor, coma, seizures
• K^{+ ​}
  
  • U waves on EKG, flattened T waves, arrhythmias, muscle spasms
• Ca²⁺
  
  • Tetany, seizures, QT prolongation
• Mg²⁺
  
  • Tetany, torsades de pointes, hypokalemia
• PO₄^3-
  
  • Bone loss, osteomalacia (adults), rickets (children)

Question 19

Electrolyte disturbances: High serum concentrations

• Na⁺
• K⁺
• Ca²⁺
• Mg²⁺
• PO₄^3-

Answer 19

• Na⁺
  
  • irritability, stupor, coma
• K⁺
  
  • wide QRS and peaked T waves on EKG, arrythmias, muscle weakness
• Ca²⁺
  
  • “Stones (renal), Bones (pain), Groans (abdominal pain), Thrones (↑ urinary frequency) and Psychiatric Overtones (anxiety, AMS)”
• Mg²⁺
  
  • ↓ DTRs, lethargy, bradycardia, hypotension, cardiac arrest, hypocalcemia
• PO₄^3-
  
  • renal stones, metastatic calcifications, hypocalcemia

Question 20

Features of Nepritic Syndrome:

Answer 20

due to GBM disruption

• HTN
• ↑ BUN and creatinine
• azotemia
• oliguria
• hematuria
• RBC casts
• proteinuria < 3.5 g/day

Question 21

Features of Nephrotic Syndrome:

Answer 21

due to podocyte disruption → charge barrier impaired

• massive proteinuria (> 3.5 g/day) w/ hypoalbuminemia
• hyperlipidemia → fatty casts
• edema

Associated with hypercoagulable state (loss of AT III in urine) and ↑ risk of infection (loss of Ig in urine)

Question 22

List the nephritic syndromes:

Answer 22

1. Acute poststreptococcal glomerulonephritis
2. Rapidly progressive glomerulonephritis
3. IgA nephropathy (Berger disease)
4. Alport syndrome
5. Membranoproliferative glomerulonephritis

Question 23

List the nephrotic syndromes:

Answer 23

1. Focal segmental glomerulosclerosis
2. Minimal change disease
3. Membranous nephropathy
4. Amyloidosis
5. Diabetic glomerulonephropathy

Question 24

List the nephritic-nephrotic syndromes:

Answer 24

1. Diffuse proliferative glomerulonephritis
2. Membranoproliferative glomerulonephritis

Question 25

Which nephritic syndrome is most commonly seen in children?

Answer 25

acute poststreptococcal glomerulonephritis

Question 26

What is the most common cause of death in SLE?

Answer 26

diffuse proliferative glomerulonephritis

Question 27

Henoch-Schölein purpura = ….

Answer 27

Henoch-Schölein purpura = IgA nephropathy

Question 28

Acute Poststreptococcal Glomerulonephritis

• Pathology
  
  • LM
  • EM
  • IF
• Clinical Features
  
  • Epidemiology
  • Symptoms
  • Labs
  • Treatment

Answer 28

• Pathology
  
  • LM: glomeruli enlarged and hypercellular
  • EM: subepithelial immune complex humps
  • IF: (starry sky) granular appearance (lump bumpy)
• Clinical Features
  
  • Epidemiology: in children ~2 weeks after group A strep infection of skin or pharynx; Type 3 hypersensitivity
  • Symptoms: peripheral and periorbital edema; cola-colored urine
  • Labs: ↑ anti-DNase B titers; ↓ complement levels
  • Treatment: self-limited

Question 29

Rapidly Progressive (crescentic) Glomerulonephritis

• Pathology
  
  • LM & IF:
• Associated disease processes
• Clinical Features
  
  • Symptoms
  • Treatment

Answer 29

• Pathology
  
  • LM & IF: crescent moon shape
    
    • consists of fibrin and plasma proteins with glomerular parietal cells, monocytes/macrophages
• Associated disease processes
  
  • Goodpasture syndrome – type 2 hypersensitivity
    
    • Ab to GBM and alveolar basement membrane → linear IF
  • Granulomatosis w/ polyangitis (Wegener’s)
    
    • PR3-ANCA/c-ANCA
  • Microscopic polyangitis
    
    • MPO-ANCA/p-ANCA
• Clinical Features
  
  • Symptoms: Hematuria/hemoptysis
  • Treatment: emergent plasmapheresis; poor prognosis

Question 30

Diffuse Membranoproliferative Glomerulonephritis

• Causes
• Pathology
  
  • LM
  • EM
  • IF
• Clinical associations

Answer 30

• Causes:
  
  • 2/2 to SLE or membranoproliferative glomerulonephritis
• Pathology
  
  • LM: “wire-looping” of capillaries (“wire-lupus”)
  • EM: subendothelial (sometimes intramembranous) IgG-based ICs often with C3 deposition
  • IF: granular
• Clinical associations:
  
  • most common cause of death in SLE
  • often presents as nephrotic and nephritic syndrome concurrently

Question 31

IgA nephropathy

• Pathology
  
  • LM:
  • EM:
  • IF:
• Associated with ….
• Clinical features

Answer 31

• Pathology
  
  • LM: mesangial proliferation
  • EM: mesangial IC deposits
  • IF: IgA-based IC deposits in mesangium
• Renal pathology of Henoch-Schölein purpura
• Clinical features:
  
  • often presents with renal insufficiency or acute gastroenteritis
  • episodic hematuria w/ RBC casts

Question 32

• What is the mutation in Alports syndrome?
• How is Alport syndrome inherited?
• What are the clinical signs/symptoms of Alport syndrome?
• What is the appearance on EM?

Answer 32

• What is the mutation in Alports syndrome?
  
  • mutation in type IV collagen → thinning and splitting of GBM
• How is Alport syndrome inherited?
  
  • X-linked
• What are the clinical signs/symptoms of Alport syndrome? (“Can’t see, can’t pee, can’t hear a buzzing bee”)
  
  • Eye problems, glomerulonephritis, sensorineural deafness
• What is the appearance on EM?
  
  • “basket-weave” appearance

Question 33

Membrano-proliferative glomerulonephritis: Type I vs. Type II

1. Type I
   
   • Pathology
   • Associations
2. Type 2
   
   • Pathology
   • Associations

Answer 33

1. Type I
   
   • Pathology:
     
     • subendothelial IC deposits w/ granular IF
     • “tram-track” appearance on PAS stain and H&E stain (GBM splitting caused by mesangial ingrowth)
   • Associations:
     
     • idiopathic; often 2/2 Hep B or Hep C infection
2. Type 2
   
   • Pathology:
     
     • intramembranous IC deposits; “dense deposits”
   • Associations:
     
     • C3 nephritic factor (stabilizes C3 convertase → ↓ serum C3 levels)

• MPGN often copresents as a nephritic and nephrotic syndrome

Question 34

What is the most common cause of nephrotic syndrome in African Americans and Hispanics?

Answer 34

focal segmental glomerulosclerosis

Question 35

What is the most common cause of nephrotic syndrome in children?

Answer 35

minimal change disease

Question 36

What is the nephrotic presentation of SLE?

Answer 36

membranous nephropathy

Question 37

What is the most common cause of nephrotic syndrome in Caucasians?

Answer 37

membranous nephropathy

Question 38

Apple-green birefringerence under polarized light →

Answer 38

amyloidosis

Question 39

Kimmelstiel-Wilson lesions →

Answer 39

diabetic glomerulonephropathy

Question 40

Response to steroids:

• Focal segmental glomerulosclerosis ⇒
• Minimal change disease (lipoid nephrosis) ⇒
• Membranous nephropathy ⇒

Answer 40

Response to steroids:

• Focal segmental glomerulosclerosis
  
  • ​inconsistent response
• Minimal change disease (lipoid nephrosis)
  
  • excellent response
• Membranous nephropathy
  
  • poor response

Question 41

Focal segmental glomerulosclerosis

• Pathology
  
  • LM
  • EM
  • IF
• Clinical associations

Answer 41

• Pathology
  
  • LM: segmental sclerosis and hyalinosis
  • EM: effacement of foot process
  • IF: nonspecific for focal deposits of IgM, C3, C1
• Clinical associations
  
  • ​African Americans and Hispanics
  • Idiopathic
  • HIV infection
  • Sickle cell disease
  • heroin abuse
  • interferon treatment
  • CKD due to congenital malformation

Question 42

Minimal change disease (lipoid nephrosis)

• Pathology
  
  • LM:
  • EM:
  • IF
• Clinical associations

Answer 42

• Pathology
  
  • LM: normal glomeruli
  • EM: effacement (fusion) of foot processes
  • IF: (–)
• Clinical associations
  
  • children
  • idiopathic
  • recent infection
  • immunization
  • immune stimulus

Question 43

Membranous nephropathy

• Pathology
  
  • LM:
  • EM:
  • IF:
• Clinical associations

Answer 43

• Pathology
  
  • LM: diffuse capillary and GBM thickening
  • EM: granular (IC deposition)
  • IF: “spike-dome” appearance w/ epithelial deposits
• Clinical associations
  
  • idiopathic
  • SLE
  • Ab to phospholipid A₂ receptor
  • drugs – NSAIDs, penicillamine
  • infections – HBV, HCV
  • solid tumors

Question 44

• What is the most commonly involved organ in amyloidosis?
• What conditions is amyloidosis associated with?

Answer 44

• kidney are the most commonly involved organ
• Amyloidosis is associated with chronic conditions
  
  • mulitple myeloma
  • TB
  • RA

Question 45

Diabetic glomerulonephropathy

• Pathology
• Pathophysiology

Answer 45

• Pathology
  
  • LM: mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis
• Pathophysiology
  
  • ​Nonenzymatic glycosylation of GBM → ↑ permeability; thickening
  • Nonenzymatic glycosylation of efferent arterioles → ↑ GFR → mesangial expansion

Question 46

Casts in urine

1. RBC casts
2. WBC casts
3. Fatty casts (“oval fat bodies”)
4. Granular (“muddy brown”) casts
5. Waxy casts
6. Hyaline casts

Answer 46

1. RBC casts
   
   • glomerulonephritis, malignant HTN
2. WBC casts
   
   • tubulointerstitial inflammation, acute pyelonephritis, transplant rejection
3. Fatty casts (“oval fat bodies”)
   
   • nephrotic syndrome
4. Granular (“muddy brown”) casts
   
   • acute tubular necrosis
5. Waxy casts
   
   • ESRD/chronic renal failure
6. Hyaline casts
   
   • nonspecific, can be normal; often seen in concentrated urine samples

Question 47

• hematuria, no casts ⇒
• pyuria, no casts ⇒

Answer 47

• hematuria, no casts ⇒ bladder cancer, kidney stones
• pyuria, no casts ⇒ acute cystitis

Question 48

Causes of respiratory acidosis

Answer 48

respiratory acidosis ⇒ hypoventilation

1. airway obstruction
2. acute lung disease
3. chronic lung disease
4. opioids/sedatives
5. weakening of respiratory muscles

Question 49

Causes of anion gap metabolic acidosis w/ compensation (hyperventilation)

Answer 49

anion gap metabolic acidosis

1. Methanol (formic acid)
2. Uremia
3. Diabetic ketoacidosis
4. Propylene glycol
5. Iron tablets/Isoniazid
6. Lactic acidosis
7. Ethylene glycol (oxalic acid)
8. Salicylates (late presentation)

Question 50

Causes of non-anion gap metabolic acidosis w/ compensation (hyperventilation)

Answer 50

non-anion gap metabolic acidosis

1. Hyperalimentation
2. Addison disease
3. Renal tubular acidosis
4. Diarrhea
5. Acetazolamide
6. Spironolactone
7. Saline infusion

Question 51

Causes of respiratory alkalosis

Answer 51

respiratory alkalosis → hyperventilation

1. hysteria
2. hypoxemia (e.g. high altitude)
3. salicylates (early presentation)
4. tumor
5. pulmonary embolism

Question 52

Causes of metabolic alkalosis w/ compensation (hypoventilation)

Answer 52

metabolic alkalosis

1. loop/thiazide diuretics
2. vomitting
3. antacid use
4. hyperalodosteronism

Question 53

1. What is the most common primary renal malignancy?
2. What is the genetic association?
3. What are other clinical associations?
4. How does it metastisize?

Answer 53

1. renal cell carcinoma (RCC)
2. Associated w/ gene deletion on chromosome 3
   
   • sporadic or inherited as von Hippel-Lindau syndrome
3. Also associated w/ paraneoplastic syndromes (ectopic EPO, ACTH, PTHrP)
4. Metastasis: hematogenously
   
   • renal vein ⇒ IVC ⇒ lung and bone

Question 54

Renal oncocytoma

• Definition:
• Pathologic findings:
• Clinical presentation:

Answer 54

• Definition:
  
  • benign epithelial cell tumor
• Pathologic findings:
  
  • large eosinophilic cells w/ abundant mitochondria w/o perinuclear clearing
• Clinical presentation:
  
  • painless hematuria, flank pain, abdominal mass

Question 55

What is the most common renal malignancy of early childhood?

• Clinical presentation:
• Mutations:
• Clinical associations:

Answer 55

most common renal malignancy of early childhood ⇒ Wilm’s tumor

• Clinical presentation:
  
  • large, palpable unilateral flank mass +/- hematuria
• Mutations:
  
  • “loss of function” mutations of tumor suppresion genes WT1 or WT2 on chromosome 11
• Clinical associations:
  
  • Beckwith-Wiedmann syndrome
    
    • Wilm’s tumor, macroglossia, organomegaly, hemihypertrophy
  • WAGR complex
    
    • Wilm’s tumor, Aniridia, Genitourinary malformation, mental Retardation

Question 56

• Most common malignancy of urinary tract ⇒
• Associated with problems in your Pee SAC

Answer 56

• Most common malignancy of urinary tract ⇒ transitional cell carcinoma
• Associated with problems in your Pee SAC
  
  • Phenacetin
  • Smoking
  • Aniline dyes
  • Cyclophosphamide

Question 57

What are the risk factors for SCC of the bladder?

Answer 57

Risk factors for SCC of the bladder

1. Schistosoma haematobium infection (Middle East)
2. chronic cystitis
3. smoking
4. chronic nephrolithiasis

Chronic irritation of urinary bladder → squamous metaplasia → dysplasia → SCC