Ch 16: Kidney- Nephropathy: Congenital and Acquired (Part 1)

Question 1

The one and only Micro/Anatomy Review Card:

1. Arterial Pathway
2. What two structures apply a negative charge to prevent filtration of proteins
3. Layers filtrate must pass through
4. Primary functions of the Mesangium
5. This apparatus contains the macula densa (sensors), extraglomerular mesangila cells, and terminal afferent arteriole (secretion) and proximal efferent arteriole
6. Cortical interstitial cells secrete
7. Medullary cells elaborate

Answer 1

1. Renal artery->interlobar arteries->arcuate arteries->interlobular arteries->Afferent->Efferent arterioles->cortical parenchyma capillaries/vasa recta
2. Podocytes and Glomerular Basement Membrane (3 layers: Lamina densa, rara interna, and rara externa)
3. Fenestrations of endothelial cells, trilaminar basement membrane, and slit pore diaphragm (connects podocyte foot processes)
4. Support for glomerulus, endocytose plasma proteins, modulate glomerular filtration and generate molecular mediators (prostaglandin and cytokines)
5. Juxtaglomerular Apparatus: secretes angiotensin and renin
6. Erythropoietin
7. Prostaglandins

Question 2

Low-set ears, small receding chin, beak-like nose, and bent lower extremities are all signs of:
The most life threatening component of this “Sequence” is:
The underlying cause is:

Answer 2

Potter Sequence
Pulmonary hypoplasia (incompatible with life)
Oligohydramnios due to decreased intrauterine urine production (**Bilateral Renal Agenesis, Bilateral Renal Dysplasia, Autosomal Recessive Polycystic Kidney Disease in Infants)

Question 3

This congenital abnormality increases the risk for glomerular sclerosis in the future due to an absence of one organ

Answer 3

Unilateral Renal Agenesis

Question 4

1. The most common location for an Ectopic Kidney.

2. This kidney malformation may get stuck on the IMA and not migrate properly or increase the risk of pyelonephritis.

Answer 4

1. Abdomen

2. Horseshoe

Question 5

Undifferentiated tubular structures lined by cuboidal or columnar epithelium, NOT INHERITED, can cause cysts in kidneys (multicystic renal dysplasia), be aplastic (very small and misshapen), or obstructive urine outflow

Answer 5

Renal dysplasia: unilateral multicystic renal dysplasia is the most common cause of abdominal mass in newborn

Question 6

Dominant mutation in PKD1 or PKD2 (primary cilia of tubular epithelial cells and cell-cell adhesion complexes; defects disrupt calcium signaling from cilia)
Kidneys are markedly enlarged bilaterally. What other pathology is associated?

Answer 6

Autosomal Dominant Polycystic Kidney Disease. Manifests itself in adulthood.
**Hepatic cysts, cerebral aneurysms, and mitral valve prolapse
Kidney cysts in renal cortex and medulla

Question 7

Recessive mutation in PKHD1 (gene for fibrocystin)
Describe the difference from Autosomal Dominant Polycystic Kidney Disease in the kidney appearance. Who is commonly effected?
What other pathology is associated?

Answer 7

Autosomal Recessive Polycystic Kidney Disease. Smooth external kidney with dilated cortical and medullary collecting ducts. Found in infants. Very large kidney size causes Potter sequence.
**Congenital hepatic fibrosis and hepatic cysts

Question 8

1. Autosomal dominant defect with cysts in medullary collecting ducts that presents in the fourth decade of life with polyuria and shrunken kidney
2. Autosomal recessive defect with corticomedullary cysts with polyuria, polydipsia, and enuresis (bed wetting)
3. Cysts in the papillae that is asymptomatic in youth but with flank pain, dysuria, hematuria or gravel in urine during 30-60s

Answer 8

Medullary cystic disease

Nephronophthisis

Medullary Sponge Kidney

Question 9

Simple Renal Cysts are seen in 1/2 people over 50. What can lead to acquired cystic disease?

Answer 9

Long-term dialysis

Question 10

Nephrotic Syndrome Features:

Answer 10

Proteinuria (>3.5g/day)

Hypoalbuminemia, edema, hyperlipidemia, and *lipiduria, hypercoaguability (wasting AntithrombinIII)

Question 11

Nephritic Syndrome (Glomerulonephritis) is an INFLAMMATORY DISEASE that features:

Which resolve with treatment? Acute, rapidly progressive, or chronic

Name the 3 most common forms:

Answer 11

Hematuria (look for Red Cell Casts to know its coming from the kidney), proteinuria, decreased GFR (elevated BUN and Creatinine with oliguria, salt and water retention, hypertension and edema)

Acute and rapidly progressive (if treated aggressively) can resolve

In situ immune complex formation, deposition of circulating immune complexes, antineutrophil cytoplasmic autoantibodies (ANCA).

Side note: Nephrotic and Nephritic features can occur in almost any glomerular disease. Minimal-change glomerulopathy is exclusively nephrotic while Crescentic Glomerulonephritis is the most severe nephritic

Question 12

Two forms of anti-GBM glomerulonephritis
Five forms of immune complex glomerulonephritis
Three other forms of ANCA Glomerulonephritis

Answer 12

• Goodpasture and Anti-GMB (no lung involvement)
• IgA nephropathy and Henoch-Schonlein (both IgA), Lupus, Acute-post-strep glomerulonephritis, Membranous glomerulopathy (subepithelial dense deposits)
• Microscopic polyangitis, Wegeners, Churg-Strauss

Question 13

Nephrotic Syndrome due to effacement of podocyte foot processes; possibly due to T-lymphocyte/cytokine disorder. Is the H&E stain normal? Any immune complexes? What disease is it related to? Response to steroids?

Answer 13

Minimal Change Disease
H&E is normal, No immune complexes, Related to Hodgkins Lymphoma, Remits with steroids.
90% of childhood nephrotic syndrome

Tend to selectively loose albumin
Pathoma: Hodgkins=cytokine producing cancer, hence cytokines causing damage and response to steroids

Question 14

Disease that affects some but not all glomeruli. Common in Hispanics or African Americans. Usually idiopathic but may be due to HIV, Pamidronate (treat bone lesions), heroin, or sickle cell disease (typically these cause collapsing pattern which progresses to end stage rapidly). Tell me more about the injury that takes place and what it looks like. Two very common causes of perihilar variant.

Answer 14

Focal Segmental Glomerulosclerosis.
Injury to the podocytes can be picked up by H&E and protein and lipid accumulation causes glassy appearance (hyalinosis).
Obesity and reduced renal mass can put more pressure on the glomeruli and lead to perihilar variant (benefit from ACE inhibitors)

IMMUNE COMPLEXES ABSENT (may have trapping of IgM and C3)

Few respond to corticosteroids, CAN RECUR with transplant

Question 15

Accumulation of immune complexes (typically against PLA2R in primary disease) in the SUBEPITHELIAL ZONE (called Heymann nephritis in animal models)
What would a silver stain show?
What about immunofluorescence?

Answer 15

Membranous Nephropathy (most common form in whites and Asians)
Silver stain which highlights basement membrane (and EM) shows "spike and dome" appearence
Immunofluorescence reveals "granular" IgG and C3 in capillary walls

4 stages based on severity

Pathoma says: also related to HepB/C, solid tumors, SLE, or drugs (NSAID/penicillamine)

Question 16

Non-enzymatic glycosylation leads to hyaline arteriolosclerosis which affects the efferent arteriole more and increases filtration pressure. This leads to excessive matrix and GBM production and podocyte injury. What area of the glomeruli is the characteristic site of damage and what do we call the nodules formed. What is the best Rx? What will immunofluorescence show?

Answer 16

Diabetic Glomerulosclerosis. Leads to MESANGIAL MATRIX expansion and sclerotic Kimmelstiel-Wilson nodules
Rx: blood sugar level control to prevent the glycosylation and progression of disease

Leading cause of end-stage renal disease in US
Microalbuminuria progresses to nephrotic syndrome in 10-15 yrs and progressive renal failure

Immunofluorescence will show: diffuse linear trapping of IgG, albumin, fibrinogen, and other plasma proteins in GBM

Question 17

Disease state commonly found in situations of chronic inflammation or high light chain synthesis (ie multiple myeloma). Mesangial alteration and podocyte foot processes effaced. What test do we use to differentiate?

Answer 17

Amyloidosis
Congo Red looking for apple-green birefringence in mesangium
Proteinuria is initial presentation followed by nephrotic syndrome.