Renal Pathophysiology 1 Flashcards
WHat type of collagen makes up the GBM in kidneys?
type 4
Describe the structure of the collagen?
six types of alpha chains
three alpha chains will make a triple helix monomer
each monomer has a 7S domain at amino terminus and a globular noncollagenous domain NC1 at the carboxyl terminus
Why is it important to know the structre o the GBM colagen?
because the noncolagenous domain NC1 at the carbosyl terminus is usually the antigenic site for the autoantibodies in anti-GBM nephritis
WHat are two slit pore diaphragm proteins that can be mutated in nephrotic syndrome?
nephrin and podocin
What are the three general categories of renal disease?
glomerular
tubulointerstitial
vascular
What is azotemia?
the biochemical bnormalities seen in kidney disease - increased BUN and creatinine
What are the three general causes of azotemia?
prerenal (hypoperfusion)
renal disease
post-renal obstruction of urine flow
What are the three general characteristics of nephritis syndrome?
hematuria
mild to moderate proteinuria
hypertension
What are the 5 general charcteristics of nephrotic syndrome?
majoe proteinuria - over 3.5 gram/day hypoalbuminemia edema hyperlipidemia lipiduria
What is the clinical presentation of an acute renal failure?
- rapid onset azotemia
2. oliguria or anuria
What is the clinical presentation of CKD?
GFR persistently less than 60 mL/min for at least 3 months
persistent albuminuria
How will a renal tubular defect present?
polyuria
nocturia
electrolyte imbalance
How will a UTI present?
pyruia and bacteriuria
Historially, what are the 4 stages of renal disease?
- diminished renal reserve (GFR around 50% normal, but no azotemia or symptoms)
- renal insufficiency (GFR 20-25% normal, azotemia, anemia, HTN)
- renal failure (less than 20% function, edema, metabolic acidosis, uremia(
- End-stage renal disease (GFR less than 5% normal - terminal stage of uremia)
What’s the aboslute ideal analyte to measure clearance?
inulin, but it breaks down immediately in the body so you need to do a continuous iV influsion of it
What’s the issue with creatinine as an analyte?
10-20% of the creatinine in the urine was secreted by the proximal tubule - this numbe varies among individuals, so it can overestimate the GFR by a small range or a big range depending on the person
We usually just use formulas to estimate GFR, but when do we still use clearance measurements?
with unusual body habitus
rapidly changin kidney function
patients with GFR of 60 or greater (for kidney donor evals, research protocols, etc)
What is a normal BUN?
10-20 mg/dl
What are some things that would increase the BUN and give a false positive?
increased synthesis - catabolism (burns, fevres, stress), high protein diet, GI bleed, Hemolysis, malignancy
What are some pre-renal causes of increased BUN?
decreased rneal perfusion/low flow states: hypotension/shock, CHF, dehydration, renal vein thrombosis
Why is the BUN sensitive to decreased renal perfusion?
in low flow states, the renin-angiotensin system is activated
Na and water reabsorpion is increased and urea is passively reabsorbed along with the Na and water, so you get an increase in serum BUN concentration
What is a normal creatinine range?
.7-1.5 (but remember clinical picture)
What is a normal BUN to Cr ratio?
10:1 to 20:1
An elevated BUN-Cr ratio usually means…
it’s a pre-renal condition due to dispropotionate increase in proximal urea reabsorption which accompanies the reabsorption of water
if it was renal or post renal, it would be a normal ratio
How can the FeNa help determine pre-real vs renal causes?
FeNa less than 1% favors pre-rnal because of the renin-angiotensin system activation in prerenal
FeNa over 2% favors a renal or postrenal cuase
Is it always abnormal to have proteinuria?
normal urin will actually have up to 150 mg/24 hours
What does a urine dipstick test for?
presence of albumin only - you’ll miss gamma light chains
When can you have a fals positive urine dipstick?
alkaline urine
gross hematuria
dilute urine
What test can see both albumin and light chains?
acid precipitation
What are some causes of preotinuria without renal disease?
postural orthostatic proteinuria - 3-5% of young adults
transient
functional (heavy exercise, cold exposure, fever)
CHF
massive obesity
constrictive pericarditis
renal vein thrombosis
Proteinuria with renal disease will be characterized by what if the issue is glomerular?
albumin and small globulins
Proteinuria with renal disease willb e characteried by what if the issue is tubular?
beta2 microglobulin
What percentage of people are born with urinary tract malformations congenitally?
10%
What is kidney agenesis?
the kidney fails to develop completely
bilateral is fatal
unilvetal is compatible with normal fucntion
What is renal hypoplasia?
failure of the kidney to develop to a normal size - can be bilateral or unilateral
What number of renal lboes is required for a diagnosis of hypoplasia?
6 or less (normal is 12)
What is an ectopic kidney?
located above the pelvic brim or down in the pelvis.
WHat is a horseshoe kidney>
when the two kidneys are fused at the upper or lower poles to form a single kidney
Describe cystic renal dysplasia?
enlarged, multi-cystic irregular kidneys
cysts with undifferentiated mesenchyme including cartilage, immature collecting ducts and plattened epithelium
What is the inheritance pattern for adult polycystic kidney disease?
autosomal dominant
Is polycystic kidney disease bilateral or unilateral?
bilateral
When do most people show symptoms in PKD?
it’s gradual cyst growth, and often renal function is maintained until later in life
What are the two genes associated wtih PCKD?
PKD1 on chromosome 16 - encodes polycystin1 (an integral membrane protein)
PDK2 on chromosome 4 (encodes polycystin 2, a nonspecific calcium permeable channel)
What do polycystin1 and polycystin2 have in common and why to mutations cause PKD?
THey are both found on priary cilia of the tubular cells
these cilia help orient the cells appropriately - hugely important in the kidney because the basolateral side has to be different from the luminal side, otherwise you get excretion of substances into spaces where it shouldnle, lading to cyst formation
What are the extra-renal anomalies in adult PKD?
liver cysts - usually asymptomatic
intracranial berry aneurysms - CHECK!
mitral valve prolapse
