Chapter 13 (renal)

Question 0

glomerulosclerosis: definition

Answer 0

Secondary changes in the glomeruli due to narrowing of atherosclerotic renal arteries and their branches.

Question 1

glomerulonephritis: definition

Answer 1

Antibody-mediated disease of the glomeruli.

Question 2

Polycystic kidney disease: describe the 2 forms

Answer 2

Adult form is autosomal dominant mutation of polycystin (85% -1; 15%- 2) typically presents in age 40-50.

Infantile form is autosomal recessive and causes Potter’s faces (compression due to reduced amniotic fluid volume from fetal anuria).

Question 3

multicystic renal dysplasia

Answer 3

A relatively benign disease with a unilateral enlarged kidney. Lesions can be removed without consequences, often leaving a normal kidney.

Question 4

What is the most common developmental kidney disorder?

Answer 4

one-sided renal agenesis (one kidney) or horseshoe kidney (formed by fusion of kidneys at midline).

Occur in 1:800 births.

Question 5

What are the 3 categories of glomerular diseases?

Answer 5

1. Immune-mediated (glomerulonephropathy)
2. Metabolic
3. Circulatory

Question 6

What are the 4 clinical syndromes associated with immune-mediated glomerular disease?

Answer 6

1. Acute Renal Failure (Crescentic GN, Goodpasture’s)
2. Nephritic syndrome (Acute GN, SLE, IgA nephropathy)
3. Nephrotic syndrome (Membranous nephropathy, lipoid nephrosis, focal segmental glomerulosclerosis)
4. Isolated hematuria (SLE)

Question 8

Differentiate nephrotic from nephritic syndrome:

Answer 8

Nephrotic: characterized by increased protein (>3.5) in urine, generalized edema, hypoalbuminemia, hyperlipidemia, and lipiduria. NO BLOOD!

Nephritic: characterized by hematuria (with RBC casts), edema, HTN, proteinuria (<3.5), hypoalbuminemia.

Question 9

What is the clinical significance of transitional epithelium?

Answer 9

It lines the calices, pelves, ureters, urinary bladder, and most of the urethra. It is impermeable to urine and water.

Question 10

Which portion of the tubule is most susceptible to damage via hypoxia or anoxia?

Answer 10

Proximal tubule.

Question 11

Uremia: definition

Answer 11

“poisoning with urine” due to renal failure or inability to filter/secrete toxic wastes. It is characterized by retention of water, electrolytes, and nitrogen-rich wastes (measured by blood urea nitrogen – BUN).

Question 12

Correlate the pathogenesis to the symptoms of autosomal dominant polycystic kidney disease:

Answer 12

A mutation in the gene encoding polycystin-1 (or 2), a cell-cell adhesion molecule. The result is tubular obstruction and the formation of multiple cysts on the kidneys BILATERALLY. Cystic changes impair renal function and cause enlargement of the kidneys.
Most pts. develop renal failure by age 40-50

Question 13

What is multicystic renal dysplasia?

Answer 13

In contrast to ADPKD, multicystic renal dysplasia is usually unilateral and the lesions can be removed without consequence.

Question 14

List the important metabolic glomerulopathies:

Answer 14

Diabetes and Amyloidosis

Question 15

Explain how circulatory disorders affect the glomeruli:

Answer 15

1. Atherosclerosis of the renal arteries causes hypoperfusion leading to involution and hyalinization of the glomeruli.
2. Sudden onset HTN (malignant) causes fibrinoid necrosis of the glomerular capillaries.
3. DIC- formation of microthrombi in the glomerular capillaries.

Question 16

Explain the pathogenesis of acute glomerulonephritis (AGN) and correlate the pathologic and clinical findings:

Answer 16

immune-mediated inflammatory glamerulopathy that occurs 1-2 weeeks after an acute infection (usually strep), and is common in children. Antigen-antibody complexes accumulate in the glomeruli and recruit inflammatory cells and complement.

Histologically the glomeruli are hypercellular, with fusion of foot processes, narrowed capillaries, and increased numbers of mesangial cells and PMNs. Immunofluorescence reveals subepithelial immune complexes (humps).

Clinically patients present with oliguria, murky brown urine, edema (esp periorbital–due to Na retention), headache, somnolence.

Labs show a nephritic syndrome (blood, albuminuria), elevated renin.

Question 17

Explain the pathogenesis of crescentic glomerulonephritis and relate the pathologic and clinical findings:

Answer 17

Crescentinc glomerulonephritis usually occurs after focal necrosis of glomerular capillaries, as can occur in Goodpasture’s syndrome (anti-collagen IV), Wegener’s (anti-neutrophil cytoplasmic antigen), or in polyarteritis nodosa and poststreptococcal glomerulonephritis.

Pathogenesis is formation of an exudate in bowman’s space. Macrophages are replaced by fibroblasts which lay down collagen causing fibrosis and ultimately destruction of the glomerulus.

Clinically, this results in nephritic syndrome, oliguria or anuria, and rapidly progressive glomerulonephritis (RPGN) - this is Acute Kidney Failure.

Question 18

Explain the pathogenesis of membranous nephropathy and relate the pathologic and clinical findings:

Answer 18

Immune-mediated and characterized by diffuse thickening of the glomerular basement membranes secondary to accumulation of immune complexes. Usually complexes are idiopathic, but can be complexes from tumor, drugs, or infection (hepB, treponema pallidum).

Histologically glomerulii have thickened basement membranes, but are normocellular. Immunofluorescence reveals even, granular deposits of IgA and C3 throughout basement membrane.

Clinically patients present with NEPHROTIC syndrome (no evidence of inflammation). Prognosis is rule of 1/3.

Question 19

How is lipoid nephrosis diagnosed?

Answer 19

AKA minimal change disease. Pt. (usually a child) will present with NEPHROTIC syndrome. Tx presumably with corticosteroids. If it responds, it’s minimal change. If it doesn’t, get a biopsy. It’s probably FSG.

Light microscopy is normal. Immunofluorescence is negative. EM will show fusion of foot processes.

Question 20

Focal segmental glomerulosclerosis: differentiate primary from secondary.

Answer 20

Primary: nephrotic syndrome of kids. Clincially not distinguishable from minimal change, but will not respond to steroids.

Secondary occurs in obese people, those with Sickle Cell, and those with HIV (worst prognosis).
Focal- affects less than half of glomeruli. Segmental- only some capillaries in affected glomerulus are scarred.

Question 21

What do most forms of chronic proliferative glomerulonephritis have in common?

Answer 21

it is essentially the progression of other nephrotic or nephritic syndromes including IgA nephropathy, FGN, and especially SLE glomerulonephritis.

They all have a chronic course, don’t respond to treatment (except SLE which responds to steroids), and slowly but inexorably lead to ESRD.

Question 22

What is the cause of end-stage kidney disease and how does it present clinically?

Answer 22

It is the progression of any glomerulopathy resulting in widespread fibrosis and destruction of glomeruli. Grossly, kidneys are shrunken bilaterally with granular surface. Histology shows hyalinization of glomeruli and tubular atrophy.

Question 23

How does diabetes mellitus affect the kidneys?

Answer 23

Deposition of glucose in the lumen of the arterioles causes hyalinosis, thickening of the vessel wall, and narrowing of vascular lumen. This ultimately leads to ischemia and tubular atrophy, along with activation of the RAA. Ultimately this can cause papillary necrosis and post-renal disease.

The glomerular basement membrane thickens and there is hypertrophy of the mesangial matrix.

DM pts are also susceptible to pylonephritis.

Question 24

List the 4 most common forms of kidney stones:

Answer 24

1. Calcium stones (75%- associated with hyperexcretion of Ca, often inherited)
2. Struvite stones (15%- complication of UTI, larger and more irregular, can fill whole renal pelvis)
3. Uric acid stones (5%- most pts. have gout, not all though).
4. Cystine stones (1%- associated with rare genetic conditions).

Question 25

What are the common predisposing conditions for ascending and descending UTIs?

Answer 25

Descending- Septicemia- usually originating from infection of endocardium, lungs, or GI tract.

Ascending- sexual intercourse, anatomic anomaly causing vesicoureteric reflux, BPH, tumors in bladder, pregnancy, congenital megauriter, stones, catheterization or surgery.

Question 26

Describe the histology of chronic cystitis:

Answer 26

Mucosa of bladder includes foci of hemhorrage, ulceration, or thickening. Wall is thickened (especially in chronic obstruction).

Question 27

Explain how circulatory collapse causes renal tubular necrosis:

Answer 27

Renal tubular necrosis occurs when the kidneys are hypoperfused OR injured by NSAIDs. Reduction in blood flow is more prominent in the cortex than the medulla, and the PCT is affected first.

Pre-renal disease becomes renal disease and Pt must be put on hemodialysis for 2-3 weeks until kidney function can recover.

Question 28

Explain the effects of HTN on the Kidneys:

Answer 28

Idiopathic HTN stimulates constriction of renal arteries and arterioles. Ultimately continuous contraction results in thickening of arterial walls. Arteries become fibrotic and multilayered. Arterioles become hyalinized (protein and neutrophils).

In malignant HTN, arterioles do not have time to adjust and undergo fibrinoid necrosis and hyperplasia of smooth muscle. Result is onion ring-like lesions.

In both cases, reduced flow to Juxtamedullary apparatus will activate RAA and exacerbate HTN.

Question 29

List 4 common tumors of the urinary tract:

Answer 29

1. Bladder tumor (most common, usually transitional cell carcinoma)
2. Renal cell carcinoma
3. Urothelial carcinoma of the renal pelvis
4. Wilms’ tumor

Question 30

Compare renal cell carcinoma and Wilms’ Tumor:

Answer 30

RCC: Males>females; med. age = 55yo. Associated with smoking, von Hippel-Lindau syndrome. 10% present with classic triad (hematuria, flank pain, palpable abdominal mass). Most have non-specific sx (weight loss, fever, hypertension, paraneoplastic sx like hypercalcemia, erythrocytosis). Most are found by CT by accident. Histologically, tumor is sharply demarkated from remainder of parenchyma and usually still encapsulated. Made of cuboidal cells like in renal tubule. Tx is surgery, prognosis is pretty bad ( is a tumor of children (the most common solid tumor of infants and young children) and usually presents at age 2-4. Asymptomatic except for palpable abdominal mass. Composed of immature kidney cells (like those in fetus). Therapy is curative 85% of time and includes surgery and chemotherapy.

Question 31

Compare renal cell carcinoma and urothelial carcinoma or the renal pelvis:

Answer 31

Urothelial carcinoma of the renal pelvis is a papillary neoplasm that usually presents with hematuria or urinary obstruction and colics. Survival is 70%.

Question 32

Correlate the macroscopic and microscopic features of urinary bladder carcinoma with the clinical features:

Answer 32

Occurs in adults 60-80 yo, occurs twice as often as RCC, but results in same number of deaths. On gross exam, tumors are papillary (wart-like) or flat but most are made of transitional epithelium and flat lesions tend to have worse prognosis.

Usually presents as dysuria, hematuria, abdominal pain, and other sx of post-renal disease.