Midterm 2 (Kidney) Flashcards
What are the functions of the kidney? What are the disorders related to each?
- excretion of substances: endogenous wastes, exogenous toxins, drugs
- uremia - NaCl balance: regulation of ECF volume, plasma volume, blood pressure
- hypertension, edema - Water balance: regulation of osmolality and ECF Na+ concentration
- hyponatremia - K+ balance
- hyperkalemia - Acid-base balance
- acidosis - PO4 and Ca2+ balance; activation of vitamin D
- bone disease - Secretion of erythropoietin
- anemia
What are the principles of kidney physiology?
- Maintain high and constant glomerular filtration rate (150-180 L/day) to excrete toxic substances
- To maintain extraordinarily high filtration rate requires very high renal blood flow; 25% of cardiac output
- Regulate excretion of NaCl and water to achieve balance by regulating their reabsorption, not changing GFR
- Protection of adequate ECF volume, plasma volume, and blood pressure almost always takes precedence over all other regulation
What is the difference between filtration, reabsorption, secretion, and excretion?
Filtration:
Occurs in the glomerulus.
The process by which blood plasma (minus large proteins and cells) is filtered out of the blood into the Bowman’s capsule to form glomerular filtrate.
Reabsorption:
Occurs primarily in the proximal tubule and other parts of the nephron.
Involves the movement of essential substances (water, ions, glucose) from the filtrate back into the bloodstream.
Secretion:
Happens mostly in the distal tubule and collecting ducts.
The process where certain substances (like hydrogen ions, potassium, and toxins) are actively transported from the blood into the filtrate to be eliminated.
Excretion:
Final step where the urine (containing waste products) is expelled from the body via the ureters, bladder, and urethra.
What is the formula for the amount excreted ?
amount excreted = amount filtered - amount reabsorbed + amount secreted
What does filtration depend on?
size and charge
- positive charge filters filtration because of negative charge of the glomerular filtration barrier
most plasma proteins (albumin) are excluded, electrolytes and water are freely filtered
What is the formula for GFR? What is the filtration fraction?
GFR = Kf x {(Pgc -Pbs)-π gc}
Kf: function of permeability and surface area of capillary
Pgc: Glomerular capillary hydrostatic pressure
Pbs: Bowman’s space hydrostatic pressure
π gc: Glomerular capillary oncotic pressure
20%: for every 100 mL of plasma entering via the afferent arterioles, 20 mL is filtered, 80 mL exit via efferent arteriole
How does arteriole constriction and dilation affect the GFR?
afferent arteriole
- constriction: reduces Pgc and GFR
- dilation: raises Pgc and GFR
efferent arteriole
- constriction: raises Pgc and GFR
- dilation: reduces Pgc and GFR
What happens in states of low renal perfusion pressure?
dilation of afferent arteriole , constriction of efferent arteriole maintains GFR
prostaglandins are mediators of afferent arteriole dilation and angiotensin II is major mediator of efferent arteriole constriction
- NSAIDS block prostaglandin synthesis
What are the two mechanisms for afferent constriction in response to increased renal perfusion pressure?
- Myogenic response: increased blood pressure stretches smooth muscle in afferent arteriole, mechanosensitive ion channels are activated, Ca2+ influx causes muscle contraction, afferent arteriole constricts, reducing blood flow to stabilize filtration.
- Tubuloglomerular feedback: increase GFR, increase NaCl to macula densa, increase NaCl entry by Na-K-Cl cotransporter, release of paracrine factors (adenosine) that constrict afferent arteriole
What are the roles of tubuloglomerular feedback?
- maintain constancy of GFR despite changes in blood pressure
- prevent glomerular capillary hypertension and damage
- prevent against ECF and plasma volume depletion and hypotension if tubular function is impaired
- toxic injury to proximal tubule, decrease NaCl reabsorption, increase NaCl in tubular fluid, afferent arteriole constriction, lowers Pgc, lowers GFR
What is renal clearance? What are extreme examples?
the volume of plasma completely cleared of the substance by excretion into the urine per unit time
max: substance is completely cleared from all the plasma that perfuses into the kidney; clearance = renal plasma flow (RPF)
min: substance is not at all removed
How do you calculate renal clearance?
amount removed from the plasma/time = amount excreted in the urine/time
clearance = (V/t)(Ux)/Px
- substance filtered but no reabsorbed or secreted (inulin, creatinine): GFR x plasma concentration = urine flow rate x urine concentration
- GFR(Px) = (V/t)(Ux) - substance secreted and completely removed from plasma (PAH): RPF(Px) = (V/t)(Ux)
What is the difference between GFR and RPF?
GFR: amount filtered by the kidney
RPF: total amount of plasma that passes through the kidney
What can we learn from measuring the clearance?
- GFR by measuring the clearance of a substance filtered but not reabsorbed or secreted
- RPF by measuring the clearance of a substance secreted and completely cleared
- Substance that is filtered and reabsorbed, clearance < GFR
- Substance that is filtered and secreted, clearance > GFR
Substance falls between RPF and 0.
How is creatinine used and cleared?
substance is cleared by GFR and endogenously produced at constant rate (not reabsorbed or secreted)
steady state plasma concentration is inversely proportional to GFR
GFR x plasma creatinine = urine flow rate x urine [creatinine]
urinary excretion rate of creatinine = production rate of creatinine
GFR x plasma [creatinine] = production rate of creatinine = constant
changes in plasma concentration used to estimate changes in GFR
Describe sodium transport along the nephron
filtered Na+ > 25,000 meg/day
Proximal tubule: 65-70% filtered load
Thick ascending limb: 25% filtered load
Distal convoluted tubule: 5% filtered load
Collecting tubule: 1-3% filtered load
Urinary excretion: <1% filtered load
What is the difference between paracellular and transcellular routes?
para: between tight junctions of cells
trans: through the cell
How do the nephron segments differ?
- Mechanism of apical membrane Na+ entry and its regulation
- Targets of action of diuretic drugs
- Permeability to water
- Leakiness of tight junctions and importance of paracellular pathways
- Pathways for Cl- reabsorption
- Addition pathways for K+ transport
Describe transport in the proximal tubule.
- Reabsorption of Na+/glucose cotransporter and Na-H exchange into the cell from lumen
- Na/K pump out of cell into interstitium
- Complete reabsorption of filtered glucose, amino acids, and bicarbonate
- High water permeability
- Highly leaky tight junctions allow substantial reabsorption of Cl, Na, and K down passive gradient from water reabsorption
What affects Na+ reabsorption in the proximal tubule?
- sensitive to inhibition by carbonic anhydrase inhibitors and SGLT2 (sodium glucose transport) inhibitors
- Na-H exchange is stimulated by angiotensin II and renal sympathetic nerves; inhibited by dopamine
- acute elevation of blood pressure inhibits Na+ reabsorption by local paracrine signaling mechanisms (eicosanoids and NO)
Describe transport in the thick ascending limb.
- Na+/2Cl-/K+ cotransport into the cell
- Na/K pump out of the cell into the interstitium
- Low permeability to water, so urine is diluted as solutes get reabsorbed
- Generates high solute concentration in the interstitium to allow for concentration of the urine
Loop diuretics block #1
NaCl reabsorption stimulated by anti-diuretic hormone (ADH) and by angiotensin II
Describe transport in the distal convoluted tubule.
- Na/Cl cotransport
- Na/K pump
- Low water permeability so urine is diluted
thiazide diuretics affect #1
NaCl reabsorption stimulated by angiotensin II and renal sympathetic nerves
inhibited by high plasma K+, stimulated by low plasma K+
Describe transport in the collecting tubule.
- Reabsorption by epithelial Na channel (ENaC)
- Cl- reabsorption is part paracellular
- Site of K secretion = major determinant of K excretion
without ADH, very low water permeability, so urine is dilute
with ADH, high water permeability
Explain K-sparing diuretics.
ENaC is site of “K-sparing” diuretics amiloride
- blocks sodium reabsorption
- promotes diuresis (increase urine production)
ENaC: Na reabsorption and K secretion stimulated by aldosterone
- Aldosterone antagonists like spironolactone are K-sparing
What stimulates K secretion in the collecting tubule?
- high plasma [K+]
- high aldosterone
- high luminal flow rate
- high luminal Na delivery
- diuretics acting upstream (loop, thiazide)
What inhibits K+ secretion in the collecting tubule?
- low plasma [K+]
- low aldosterone
- low luminal flow rate
- low luminal Na delivery
- K-sparing diuretics
