Renal 1

Question 1

glomeruli histology

Answer 1

Network of capillaries between afferent arteriole (bringing blood to the capillary bed) and efferent arteriole (drains blood away from capillary bed). The capillary wall consists of endothelium, basement membrane and epithelium (lining the urinary space). The epithelial cells have many finger-like processes that come from the cell body and contact the basement membrane. A membrane connects adjacent processes (called the slit diaphragm) and is important in preventing proteinuria. The capillary wall is permeable to water and small molecules and impermeable to albumin and larger proteins. The capillaries are supported by connective tissue called the mesangium.

Question 2

tubule histology

Answer 2

The filtrate from the glomeruli travels through the system of tubules. The tubular epithelium reabsorbs some substances and secretes other substances, eventually forming urine

Question 3

interstitium histology

Answer 3

Formed by collagen and blood vessels between the tubules and glomeruli.

Question 4

vasculature histology

Answer 4

The efferent arterioles supply the capillary bed around some of the tubules (vasa recta). Absence of blood flow through the glomeruli reduces oxygen delivery to the tubules.

Question 5

azotemia

Answer 5

Elevation of the blood urea nitrogen (BUN) and creatinine levels, due to decreased filtration of blood through the glomeruli (decreased glomerular filtration rate).

Question 6

uremia

Answer 6

Association of azotemia with clinical signs and symptoms, including gastroenteritis, peripheral neuropathy, pericarditis, dermatitis, hyperkalemia, and metabolic acidosis.

Question 7

acute nephritic syndrome

Answer 7

Results from glomerular injury and is characterized by acute onset of hematuria, mild to moderate proteinuria, azotemia, and hypertension.

Question 8

nephrotic syndrome

Answer 8

Glomerular syndrome characterized by heavy

proteinuria (> 3.5 grams per day), hypoalbuminemia, severe edema, hyperlipidemia, and lipiduria.

Question 9

acute renal failure

Answer 9

Acute onset of azotemia with oliguria (or anuria).

Question 10

Autosomal dominant (adult) polycystic kidney disease Clinical presentation

Answer 10

seen in 1 out of every 500-1000 people,
characterized by multiple expanding cysts in both kidneys. Gradual onset of renal failure in adult, urinary tract hemorrhage (hematuria), pain, hypertension, urinary tract infection.

Question 11

Autosomal dominant (adult) polycystic kidney disease etiology

Answer 11

defective gene is PKD1 (in 90% of families) located on chromosome 16. The gene encodes for polycystin-1

Question 12

Autosomal dominant (adult) polycystic kidney disease Extrarenal pathology

Answer 12

1/3 of patients have cysts in liver; aneurysms
may develop in the circle of Willis (intracranial)
saccular (“berry”) aneurysms affecting circle of Willis (30%)

Question 13

Autosomal dominant (adult) polycystic kidney disease Pathology

Answer 13

very large (up to 4 kg) kidneys with numerous cysts that
arise in every part of the tubular system
•Histopathology
–Cysts arise from all levels of the nephron
•Clinical: flank pain around 4th decade, hematuria, hypertension and UTI, renal failure

Question 14

Autosomal recessive (childhood) polycystic kidney disease clinical

Answer 14

renal failure develops from infancy to several years of age – rare; seen in 1 in 20,000 live births. Due to mutations in the PKHD1 gene
•Defective protein: fibrocystin

Question 15

Autosomal recessive (childhood) polycystic kidney disease Extrarenal pathology

Answer 15

almost all have liver cysts and progressive liver fibrosis

Question 16

Autosomal recessive (childhood) polycystic kidney disease pathology

Answer 16

numerous small uniform-size cysts from collecting tubules

in cortex and medulla

Question 17

Mechanisms of glomerular injury

Answer 17

1. Immune complex deposits in glomerular basement membrane (GBM)
   or mesangium. These may result from circulating immune complexes that deposit in the glomerulus or circulating antibodies directed against glomerular components or non-glomerular antigens “planted” in the glomerulus.
2. Epithelial and endothelial cell injury.

Question 18

Pathologic evaluation of kidney biopsies

Answer 18

1. Light microscopy - In addition to H+E stain, PAS, trichrome (collagen) and Jones stains PAS/methenamine silver- for basement membrane evaluation) are routinely done.
2. Immunofluorescence - Antibodies to immunoglobulin and complement, tagged with a fluorescent molecule, are used to identify immune complexes.
3. Electron microscopy - Identification of immune complexes, epithelial cell changes, basement membrane morphology and other changes.

Question 19

nephrotic syndrome

Answer 19

Heavy proteinuria- lead characteristic, hypoalbuminemia, severe edema (most obvious clinical sign), hyperlipidemia and lipiduria
•Caused by increased glomerular capillary permeability to plasma proteins:
–Minimal change disease
–Focal segmental glomerulosclerosis
–Membranous nephropathy
–Nodular glomerulosclerosis (diabetes mellitus)

Question 20

minimal change disease

Answer 20

a) most common cause of nephrotic syndrome in children. (2/3rds of all cases)
b) pathology - normal-appearing glomeruli by light microscopy; no immune complexes; electron microscopy demonstrates effacement of epithelial cell foot processes
c) good response to corticosteroid treatment (especially in children)
•Pathology
LM – Normal-appearing glomeruli
IF - No immune complex deposits
EM - Foot process effacement

Question 21

Focal and segmental glomerulosclerosis

Answer 21

a) one of the most common causes of nephrotic syndrome in adults.
b) may be primary (idiopathic) or secondary to other glomerular diseases, loss or scarring of other glomeruli, or genetic.
c) pathology - partial (segmental) sclerosis of some (focal) glomeruli characterized by increased mesangial matrix collagen with obliteration of capillary loops. The idiopathic form has no immune complexes.
d) poor response to corticosteroid treatment – renal failure in 50% after 10 yrs.
•Pathology
-LM – focal (some glomeruli) and segmental (part of involved glomerulus) sclerosis with obliteration of capillary loops
-IF and EM – no immune complex deposits in the primary (idiopathic) form

Question 22

membranous nephropathy (glomerulonephritis)

Answer 22

a) most common in adults age 30-50, may affect children
b) may be primary (disease limited to the kidney) or secondary to infection, malignancy, SLE, or drugs.
c) pathology - immune complexes in the epithelial side (subepithelial) of the GBM demonstrable by immunofluorescence and electron microscopy
d) poor response to corticosteroid treatment, with 40% developing
renal failure in 2-20 years

•Pathology

• LM: nearly normal
• IF: Immune complex deposits
• EM: deposits in subepithelial side of the GBM

Question 23

Glomerular disease in diabetes mellitus

Answer 23

•Renal failure is 2nd only to MI as cause of death in DM
•Pathology
-LM - Nodular glomerulosclerosis
-IF – No immune complex deposits
-EM - Thick GBM
•Other changes
-Hyaline arteriolosclerosis
-Atherosclerosis
-Nephrosclerosis      

a) minimal proteinuria progresses, over 10-15 years, to severe proteinuria.
b) thick glomerular basement membranes, diffuse increase in mesangial matrix and formation of mesangial nodules (the latter is nodular glomerulosclerosis or Kimmelstiel-Wilson lesion)

Question 24

Nephritic Syndrome

Answer 24

• Characterized by acute onset of 1) hematuria, 2) oliguria & azotemia and 3) hypertension
• Proliferation of cells within the glomeruli, accompanied by inflammatory cells
• Inflammation severely injures capillary walls
• Results in blood passing into the urine as well as reduced GFR

Question 25

Acute postinfectious (poststreptococcal) glomerulonephritis

Answer 25

a) most commonly occurs in children 1-4 weeks after a bout of streptococcal pharyngitis (other infections as well) b) pathology - proliferation of endothelial and mesangial cells- may develop cellular crescents ; infiltration of neutrophils and monocytes; immune complexes in GBM and sometimes in the mesangium. c) progression to chronic renal disease is more likely in adults. •Pathologic Findings -LM - proliferation of endothelial and mesangial cells, inflammatory cells; may develop cellular crescents -IF – immune complex deposition, granular -EM – immune complexes in GBM + mesangium

Question 26

. IgA nephropathy

Answer 26

a) usually occurs in children and young adults b) hematuria is noted 1-2 days after non-specific upper respiratory tract viral infection, resolves then recurs c) pathogenesis may involve increased IgA production d) when the glomerular disease is associated with systemic manifestations (purpuric skin rash GI pain and arthritis), this is called Henoch-Schönlein purpura. e) pathology - mesangial deposition of immune complexes containing IgA and variable proliferation of mesangial and endothelial cells. Occasionally there is epithelial cell proliferation with crescents. •Pathology -LM – variable mesangial cell proliferation -IF and EM – immune (IgA) complexes within the mesangium

Question 27

Crescentic or Rapidly Progressive Glomerulonephritis

Answer 27

1. May be associated with antibodies directed against a glomerular basement antigen, deposition of immune complexes, or lack of immune complex deposition (called pauci-immune glomerulonephritis). •Clinical syndrome, not a specific form of glomerulonephritis •Progressive loss of renal function; lab finding c/w nephritic syndrome; severe oligouria •Death from renal failure in weeks to months if untreated •Characteristic finding is crescentic glomerulonephritis due to proliferation of epithelial cells with infiltration of histiocytes •Several different disorders: –Anti-GBM antibody disease (12% of cases) –Immune complex disease (44% of cases) –Pauci-immune, lack of anti-GBM or immune complexes (44% of cases)

Question 28

CHRONIC (END-STAGE) RENAL DISEASE

Answer 28

A. Loss of glomeruli and tubules leads to fibrosis. Damaged glomeruli become completely sclerotic (global sclerosis). With advanced loss of tubules and glomeruli, the remaining glomeruli develop adaptive changes. These changes eventually lead to further injury and progressive renal failure. • B. •By the time chronic glomerulonephritis is diagnosed, the original renal disease often cannot be identified Onset may be insidious - young and middle-aged adults •May be detected at routine exam by findings of proteinuria, hypertension or azotemia •Without treatment, poor prognosis •Renal dialysis and kidney transplantation are necessary for patient survival