Renal Pathology Lecture I Flashcards
What forms the backbone of the GBM?
Type IV collagen monomers. —3 alpha chains combine to for triple helix to make a monomer.
What is a large reason why the overall charge of GBM negative?
Heparin sulfate.
What is the function of the filtration slit diaphragm?
Exclusion of large proteins and albumin.
3 general categories of renal disease
- Glomerular (often immune mediated)
- Tubulointerstitial (toxic/ischemic and inflammatory)
- Vascular
Azotemia
Increased BUN and creatinine
Pre-renal causes of azotemia
Hypoperfusion (hemorrhage, shock, dehydration, CHF)
Post-renal causes of azotemia
Obstruction of urine flow (stone or tumor)
Uremia
Azotemia and clinical symtoms (gastroenteritis, anemia, peripheral neuropathy, pruritis, pericarditis etc.
Nephritic syndrome
Hematuria, mild to moderate proteinuria, HTN
Nephrotic syndrome
> 3.5g/day of proteinuria, edema, hypoalbuminemia, hyperlipidemia, lipiduria
Acute renal failure clinical presentation
- -Rapid onset azotemia
- -Oliguria or anuria
- -Due to glomerular, tubulointerstitial, or vascular disease.
Chronic renal failure clinical presentation
–GFR
Clinical presentation of renal tubular defects
Polyuria
Nocturia
Electrolyte imbalances
4 stages of renal disease
- Diminished renal reserve
- Renal insufficiency
- Renal failure
- End-stage renal disease
Diminished renal reserve
GFR around 50% of normal. Normal range BUN/Cr
Asymptomatic
Renal insufficiency
GFR 20-50% of normal
Azotemia
Anemia
HTN
Renal failure
GFR
End stage renal disease
GFR
Clearance equation and definition
–Approximation of GFR
C=UV/P
Best analyte to measure clearance
Inulin
Cockcroft-gault formula
CrCL=((140-age)x weight (kg))/(72 x serum creatinine x0.85 (if female)
MDRD formula
GFR=175 x serum creatinine^-1.154 x age^-.203 x 0.742 (if female) and 1.212 (if black)
What is chronic kidney disease defined by?
Persistent reduction in GFR to less than 60. Less than 30 recommend seeing nephrology
When are clearance measurements still used?
- -Unusual body size
- -Rapidly changing kidney function
- -GFR 60+
BUN
- Rough est. of glomerular function
- Normal 10-20 mg/dl
- Combined w/serum creatinine, helps determine causes of azotemia
- Sensitive to decreased renal perfusion
Pre-renal factors increasing BUN
- -Increased synthesis of urea
- -Decreased renal perfusion/low flow states
Renal factors increasing BUN
Glomerular disease, ATN, interstitial disease
Post-renal factors increasing BUN
Urinary tract obstruction (BPH, prostatic carcinoma, tumor, retroperitoneal mass, urinary calculi
Factors decreasing BUN
- -Decreased synthesis
- -Hemodilution
- -Generally not diagnostically useful
Creatinine
- -Normal 0.7-1.5
- -Most found in muscle.
- -Slightly better est. of glomerular function than BUN
Pre-renal increases in creatinine
- -Increased synthesis (muscle hypertrophy, muscle necrosis, anabolic steroid use, high meat diet, intense exercise)
- -Decreased renal perfusion (CHF, hypotension, shock, etc.)
Post-renal increase in creatinine
UTI
Normal BUN: creatinine ratio
10-15: 1
When do you see elevated BUN:creatinine ration
Pre-renal conditions. Disproportionate increase in proximal urea reabsorption.
What type of BUN:creatine ratio will you see in renal disease?
Normal ratio
Fraction of excreted sodium (FeNa)
(Urine Na x plasma Cr x 100)/ (urine Cr x plasma Na)
What does it mean if FeNa
Favors pre-renal disease
What does it mean if FeNa >2.0
Favors renal disease (ATN)
Proteinuria normal value
50 mg
Tests for proteinuria
- -Dipstick test (only sensitive to albumin, pH dependent, can get false + w/gross hematuria or dilute urine)
- -Acid precipitation (detects albumin and globulins, false + w/some meds and gross hematuria)
Causes of proteinuria w/o renal disease
- Postural (orthostatic)
- Transient
- Functional (heavy exercise, cold exposure, fever)
- CHF
- Massive obesity
- Constrictive pericarditis
- Renal vein thrombosis
Proteinuria w/renal disease
- Glomerular pattern (albumin, small globulins, can reach nephrotic range)
- Tubular pattern (beta2 microglobulin, will never reach nephrotic range)
% of people w/UT malformations
10%
What 2 things account for 20% of chronic kidney disease in children?
Renal dysplasia and hypoplasia
What accounts for 10% of chronic kidney disease in adults?
Polycystic kidney disease
Kidney agenenis
- -Bilateral incompatible with life.
- -Unilateral w/normal function
- -Lack of proper ureteric bud development
Kidney hypoplasia
- -Failure to develop to normal size
- -Bilateral or unilateral
- -No scarring
- -Decreased # of renal lobes (6 or less)
- -Most cases are acquired (slow scarring)
Ectopic kidneys
–Typically found just above pelvic brim or in pelvis
Horseshoe kidney
- -Fusion of upper (10%) or lower poles (90%) to form single horseshoe shaped kidney.
- Not very uncommon
Cystic renal dysplasia
- -Unilateral or bilateral
- -Gross: Enlarged, multi-cystic, irregular
- -Micro: undifferentiated mesenchyme, cartilage, immature collecting ductules, variably sized cysts lined by flattened epithelium
- -sporadic disorder
- -Most also have lower tract anomalies
Autosomal dominant (adult) polycystic kidney disease
- -Hereditary
- -Autosomal dominant
- -Bilateral disease
- -Multiple expanding cysts destroy renal parenchyma
- -Only involving portion of kidney initially
Adult PCKD genetics
PKD1 gene on chromosome 16p13.3 in most cases
Adult PCKD gross kidney findings
- -Bilaterally enlarged kidneys, may be huge
- -Look like a bag of cysts
Adult PCKD micro findings
- -Cysts with variable lining
- -Normal parenchyma present between cysts
Clinical findings in adult PCKD
Asymptomatic
or pain and hematuria
Extra-renal anomalies in adult PCKD
Liver cysts (40% of pts)
Intracranial berry aneurysms
Mitral valve prolapse
Autosomal recessive (childhood) PCKD categories
–Perinatal
–Neonatal
–Infantile
–Juvenile
Only last 2 survive infancy
Gross findings in AR PCKD
Enlarged, smooth kidneys externally, cut sections show small cysts in the cortex and medulla
Micro findings in AR PCKD
Dilation of all collecting tubules (uniform cuboidal lining of cysts)
General info about AR PCKD
- -Bilateral
- -Liver cysts and bile duct proliferation in almost all patients
- -May see congenital hepatic fibrosis in 2 forms that survive infancy
