03: The Glomerulus & GFR Flashcards
Sodium overload
- Leads to edema (lower extremity, facial) and HTN
- Too much isotonic fluid
- nl blood sodium: 135 - 145 mEq/L H2O
- Routinely see a 5-10L gain H2O in overload
Water overload
- Normal ratio of 135-145 mEq Na/L H2O
- Overload (hypo-osmolarity): 120-130mEq/L H2O
- Neuronal dysfunction
- Somnolence and coma
- Death
Potassium overload
- Presentation: Elevated T-waves, widened QRS, arythmias, electric silence
H+ overload
- Normal: pH = 7.4; pHCO3 = 24 mM/L
- KO: pH = 7.2; pHCO3 = 16 mM/L
- Bicarbonate constantly released to atmosphere as CO2; never replaced by the CKD/KO kidney
Endocrine deficiencies
- No 1,25Dihydroxy VitD3 (calcitriol) synthesis –> ↓Ca, ↑PO4–> altered neuronal activity –> **myoclonus **(muscle spasms)
- No erythropoeitin synthesis –> anemia
- Reduced gluconeogenesis or diminished insulin degradation –> hypoglycemia (dangerous in diabetes)
Uremia
- Nitrogen waste (urea/NH4)
- Chemical damage syndrome resulting in inflammation of the pericardium, pleura and skin (serositis)
- Clinical features: pericardial rub, pericardial bleeding, tamponade physiology
- Leads to abnormal neuronal activity
- Myoclonus, drowsy confusion
The glomerulus
- Filters approximately 20% of the 1036 L of plasma delivered by blood flow over 24 hours (i.e., filters 200 L).
- Allows water, ions, low molecular weight proteins to pass into urinary space of Bowman, while preventing cells or larger molecular weight proteins from passing.
- Since 60% of body weight is water (42L), urinary space receives 4-5x our total body water/day.
- Two kidneys have 2x106 glomeruli, each one filtering 100 uL/day
The tubule
- 98-99% of filtrate is reabsorbed back into the blood via the nephron’s tubule
- Not reabsorbed is 0.5-2L excess water/day containing 2-1000 mEq Na, 15-100 mEq K, 0 mEq bicarbonate; urea, NH4 (acidified buffer) –> the final urine
Creatinine
Proportional to muscle mass, constantly produced and excreted, hence at steady state (unlike inulin).
Filtered like water, not reabsorbed.
Low level of secretion by the nephron.
Pcr at steady state = 1 mg/dL
Ucr at steady state = 2,000 mg/day
Both Pcr and Ucr are necessary to determine the GFR.
Glomerular Filtration Rate (GFR)
GFR = (Ux mg/mL x V mL/min) / Px mg/mL
Amount of plasma/min filtered through the glomerulus that is cleared of X (most often creatinine).
GFR over 90mL/min is normal unless there is other evidence of kidney disease.
Glomerular basement membrane: Integrins
Alpha3/beta1
- Interact with laminin and collagen and regulate cytoskeleton and gene expression.
- Tension in GBM results in response in podocytes via integrin signaling –> activated gene expression.
Alport syndrome
- X-linked dominant disorder
- Alpha5 chain of collagen defective and NC1 missing
- Collagen IV chains have very short half life and GBM is unstable
- Transplantation difficult
Piersons syndrome
- Rare autosomal recessive mutation of laminin-beta2
- Same phenotype as Alports syndrome
Membranous nephropathy
Thickening of part of the glomerular basement membrane.
Due to Ig deposits in a sub-epithelial compartment.
Leads to significant protein leak into urine.
Slit diaphragm adhesion junction molecules
- **Nephrin **= lipid raft protein forming complexes with podocin and neph1 –> ligate opposing membranes of food processes by homo and hetero-dimerization
- Nephrin: creates molecular sieve that regulates flux across urinary space
- Podocin: forms homo-oligomers and stabilizes nephrin in lipid raft
- Neph1-nephrin: signal to Nck2-Wasp
- Induce actin bundling
- Interact w/ Par3,6 polarity proteins
- Podocin-nephrin: signal to CD2AP
- Induce actin bundling
