Chapter 26: Urine Formation II: Glomerular Filtration and Blood Flow (Discussion 2) Flashcards
Urine Formation Formula
Urinary Excretion = Glomerular Filtration – Tubular Reabsorption and Tubular Excretion
Filtration (of substance) = Glomerular Filtration Rate x Plasma Concentration (x filterability)
Filtration & Reabsorption closely coordinated (avoids severe changes in urine output)
- High volume compared to urine~1.5L/day
- Filtration - 180L/day
- Reabsorption - 178.5L/day
Tubular Reabsorption
Reabsorption is highly selective
- Glucose/AA’s completely reabsorbed (Bicarb almost completely reabsorbed)
- Na+/K+/Cl- mostly reabsorbed but regulated closely
- Creatine not reabsorbed at all
Luminal Membrane
- Brush-border membrane –> increase surface area for transport and high activity
- Thin segments of loop of Henle do not have brush border
- Tight junction –> prevent fluid/solute leakage between cells
Reabsorption Path
Transcellular vs Paracellular
- Transcellular: substance transported cross tubular cell membrane and into cell
- Paracelullar: substance transported through junctional spaces between cells
- Substance must be transported through tubular epithelial membrane –> renal interstitium
- Then through peritubular capillary membrane –> blood
- Achieved through Bulk Flow (non-specific fluid/solute movement caused by hydrostatic and osmotic pressure)
Types of Transport
- Active: uses ATP, against concentration gradient
- Secondary Active Transport:
uses energy (indirectly) stored in electrochemical gradient of another molecule
- Diffusion: no ATP, down concentration gradient
- Facilitated diffusion: binds membrane protein to transport across membrane
Reabsorption of Na+
- Facilitated diffusion across luminal membrane (primarily into cell/transcellular path)
- Active transport by Na-K ATPase across basolateral membrane into interstitium
- Creates Na+ gradient used to reabsorb Na+ and many other secondary active transport processes
- Reabsorption into peritubular capillaries by ultrafiltration
Active Transport in Lumen (Na-K pump)
Na-K pump: establishes low [Na+] (major source for secondary transport) and high [K+] in luminal membrane cells
Active Transport in Lumen
- Reabsorption/secondary active co-transport
- Na/Glucose
- Na/AA
- Na/Cl
- Secretion/secondary active counter-transport
- Na/H+ (controls acidity of body fluids)
- Pinocytosis: membrane invaginates and forms vesicle around bulk substance
- Reabsorbs proteins that end up in the tubule
Tubular Maximum Transport vs Gradient-time Transport
- Active transport/facilitated diffusion has tubular maximum transport rate for a substance depending on proteins involved in transport of the substance
- Gradient-time transport has no physiological maximum rate b/c not limited by proteins
- Dependent on: electrochemical gradient, permeability of membrane to substance, time fluid with substance remained in tubule
- Glomerular filtration has potential to drastically rise
- Diabetes mellitus (high plasma glucose –> glucose in urine)
- Na+ exhibits both types of transport
- Proximal show gradient-time due to back- leakage and distal segments reabsorption can be ↑ by some hormones (ex. aldosterone) but show tubular maximum
Solvent Drag
Osmotic flow through tight junctions carrying solutes along as well
Water permeability varies by segment
Water leaving tubule also increase conc gradient of remaining solutes, increasing diffusion
Sections of the Nephron
Proximal Tubule
- Reabsorbed
- Glucose (most by first half)
- AA (most by first half)
- Protein
- Na+ (about 65% of filtered amount)
- HCO3-
- Cl-
- K+
- Secreted
- H+
- Organic acids (PAH)
- Organic bases (oxalate/urate)
- Drugs/harmful substances
- Water
- Highly permeable
- Reabsorbed (~65% of filtered amount)
- Osmolarity relatively constant
Thin Descending Limb
- Reabsorbed
- Moderately permeable to most solutes (low active transport/reabsorption)
- Secreted
- Moderately permeable to most solutes (low active transport/secretion)
- Water
- Highly permeable
- Reabsorbed
- Increasing osmolarity
Thin Ascending Limb
- Reabsorbed
- Moderately permeable to most solutes (low active transport/reabsorption)
- Secreted
- Moderately permeable to most solutes (low active transport/secretion)
- Water
- Impermeable
Thick Ascending Limb
- Reabsorbed
- Na+
- Cl-
- K+
- HCO3-
- Ca++
- Mg++
- Secreted
- H+
- Water
- Impermeable
- Decreasing osmolarity
Distal Tubule
- Reabsorbed
- Na+ (NaCL cotransporter action, inhibited by Thiazide diuretics)
- Cl-
- K+
- Ca++
- Mg++
- Secreted
- No major secretion activity
- Water
- Impermeable (also impermeable to urea)
- Decreasing osmolarity (referred to as the diluting segment)
Late Distal Tubule & Cortical Collecting Tubule
- Impermeable to urea
- Water reabsorption determined by ADH (impermeable normally, become permeable with high ADH)
- Composed of 2 types of cells
- Principal cells
- Intercalated cells
Principal Cells
Late distal tubule & cortical collecting tubule
- Reabsorbed
- Na+
- Secreted
- K+
- Site of action for “potassium sparing diuretics”
- Aldosterone antagonists: inhibit Na-K pump activity on basolateral membrane
- Na+ channel blockers: prevent Na+ from diffusing into principal cells from lumen
Intercalated Cells
(late distal tubule & cortical collecting tubule)
- Reabsorbed
- HCO3- (released in cell when H+ is formed to be secreted)
- K+
- Secreted
- H+ (energy from hydrogen-ATPase action, not secondary like other parts)
Medullary Collecting Duct
- Reabsorbed
- Urea
- Na+
- Cl-
- HCO3-
- Secreted
- H+
- Water
- Variable permeability (controlled by ADH)
Na+/2Cl-/K+ Co-transporter
- Located in thick ascending limb
- Energy supplied by Na+ gradient
- Loop diuretics (e.g. furosemide) inhibit this action –> very powerful diuretic action
Mechanisms of Pressure Natriuresis/Diuresis
- slight ↑ in GFR
- High peritubular capillary hydrostatic pressure –> ↓ reabsorption of Na/H20
- High arterial pressure –> ↓ Angiotensin II/aldosterone formation –> ↓ reabsorption of Na/H2O
Aldosterone
Increase in Na reabsorption and K secretion
Act in collecting tubule/duct
Angiotensin II
Increase in Na, water reabsorption, and H+ secretion
(also constrict efferent arterioles and increase aldosterone release)
Proximal tubule, thick ascending loop, distal/collecting tubule
Atrial Natriuretic Peptide (ANP)
Decrease in Na/water reabsorption
Distal/collecting tubule & duct
Parathyroid Hormone
Increase in Ca++ and Mg++ reabsorption
Decrease phosphate reabsorption
Proximal tubule, thick ascending loop, distal/collecting tubule
Antidiuretic Hormone (vasopressing) Mechanism
End result: increase water reabsorption
- late distal tubules, collecting tubules, collecting ducts
- binds to V2 receptors –> stimulate aquaporin-2 (AQP-2) to move to luminal membrane, cluster & fuse together to form water channels (aquaporins)
- AQP-3 & AQP-4 on basolateral membrane, permit diffusion out of cells (not regulated by ADH)
- As ADH ↓, AQPs are shuttled back to cytoplasm removing water channels
Calculating GFR
(Ucreatinine x Vurine)/ Plasmacreatinine
Can be estimated based on creatinine because creatinine is essentially freely filtered w/o significant secretion/reabsorption
Calculating Renal Plasma Flow
RPF = Us x V/Ps
- Substance S must be completely cleared for this to work (requires secretion not just filtration)
- RPF is then equal to clearance of the substance (PAH is ~90% cleared so can be an estimator)
Calculating Extraction Ratio
[Ps(renal arterial) – Ps(renal veinous)] / Ps(renal arterial)
Fraction of substance passing through kidney that is excreted
Calculating Filtration Fraction (FF)
GFR/RPF
Fraction of plasma that passes through glomerular membrane
