Renal Hemodynamics and Filtration
The volume of plasma completely cleared of a substance per unit time; measures the efficiency of eliminating substances from the body
What is clearance?
Secondary active transport which occurs in the proximal convoluted tubule (PCT); a substance is freely filtered at The glomerulus, the Na+ gradient created by the Na+/K+ ATPase drives this substance to enter via SGLT on apical side, this substance exits the cell into blood via GLUT on basolateral side, and then enters peritubular capillaries
What is glucose reabsorption?
- The corticomedullary osmotic gradient is established via different permeabilities of the descending and ascending limbs and opposite flow directions which amplify small osmotic differences into a large vertical gradient
- The corticomedullary osmotic gradient is preserved via slow blood flow in the vasa recta (a hairpin structure) which allows passive exchange; the descending vasa recta gains NaCl and urea and loses water while the ascending vasa recta loses NaCl and urea and gains water
- The corticomedullary osmotic gradient is amplified when ADH increases urea permeability in the inner medullary collecting duct
what is countercurrent multiplication, countercurrent exchange, and urea cycling
Target location of this hormone is the distal convoluted tubule and collecting duct; this hormone diffuses into the cell, binds to mineralocorticoid receptor in the cytoplasm, and then this hormone-receptor complex enters the nucleus, this causes an increased transcription of epithelial Na+ channels on apical surface, Na+/K+ ATPase on basolateral surface, and K+ channels on apical surface; main outcome is sodium reabsorption, potassium secretion, and hydrogen ion secretion
What is aldosterone?
Match the primary disorder to the changes (metabolic acidosis, metabolic alkalosis, respiratory acidosis, respiratory alkalosis)
- increased PaCO2 and decreased pH
- increased HCO3- and increased pH
- decreased HCO3- and decreased pH
- decreased PaCO2 and increased pH
what is respiratory acidosis, metabolic alkalosis, metabolic acidosis, respiratory alkalosis
- Indicates fraction of plasma flowing through the kidneys that is filtered across the glomerular capillaries
- Equal to RPF/GFR and typically has a normal value of 0.20
- efferent constriction increases this value while afferent constriction decreases this value
- a higher value indicates more plasma is filtered per unit plasma flow which increases protein concentration in peritubular capillaries which increases oncotic pressure
What is filtration fraction?
The maximum rate at which renal tubules can reabsorb or secrete a substance per unit time due to a finite number of transporters; when the filtered load is greater than this value, the excess cannot be reabsorbed and the substance appears in the urine; it indicates carrier saturation
what is tubular or transport maximum (Tm)
Match the segment with water permeability characteristics (high, none, low, or ADH dependent):
- distal convoluted tubule
- proximal convoluted tubule
- ascending limb
- descending limb
- collecting duct
- what is low, high via aquaporin 1, none, high, ADH dependent
Segment of the nephron most sensitive to a thiazide diuretic; thiazide diuretics target the Na+/Cl- cotransporter on the apical surface which increases Na+ and Cl- excretion; the small increase in Na+ excretion has a significant effect here because this site normally reabsorbs 5-7% of filtered Na+
what is the distal convoluted tubule?
A renal mechanism by which ammonia (NH3) diffuses from the renal tubular cells into the tubular lumen where it combines with H+ to form ammonium (NH4+) which is trapped in the urine because the charged NH4+ cannot easily cross the lipid membrane; it is a major renal mechanism to excrete H+ and generate new bicarbonate, prevent systemic acidosis, and maintain intracellular pH
what is diffusion/ammonia trapping?
The auto regulatory mechanisms that maintained glomerular filtration rate (GFR) despite changes in arterial pressure:
- senses stretch of the afferent arteriole caused by changes in arterial pressure; increased arterial pressure causes increased stretch of the afferent arteriole which causes reflex vasoconstriction of afferent arteriole to stabilize GFR
- senses NaCl concentration in the distal tubule; increased GFR increases NaCl delivery to macula densa which causes release of ATP/adenosine which causes afferent arteriole constriction which decreases GFR back toward normal
what is myogenic mechanism and tubuloglomerular feedback (TGF)?
Match the answers to the correct formula (net reabsorption, net secretion, filtration only)
- excreted load (EL= Urine concentration x urine flow rate) = filtered load (FL = GFR x Plasma concentration)
- EL < FL
- EL > FL
what is filtration only, net reabsorption, net secretion
When this substance binds to V2 receptor it activates adenyl cyclase, increases cAMP, and activates PKA; PKA phosphorylates aquaporin II vesicles which insert into apical membrane to increase water permeability and water reabsorbed from tubular fluid and aquaporin 3 and 4 vesicles which insert into basolateral membrane to allow water to exit into the interstitium passively; the result is that the urine becomes concentrated and plasma osmolarity decreases
What is anti-diuretic hormone (ADH)/arginine vasopressin
Match the class of diuretics to its site and function (loop, thiazide, K+ sparing, acetazolamide, mannitol):
- functions in the distal convoluted tubule via inhibition of Na+/Cl- cotransporter on the apical membrane; this inhibits Na+ and Cl- reabsorption
- functions in the collecting duct via ENaC/aldosterone receptor; increases Na+ excretion and decreases K+ secretion
- functions in the TAL via NKCC inhibition; increases Na+, K+, Cl- excretion
- functions in the thin descending loop via increasing tubular osmolarity
- functions in the proximal convoluted tubule via carbonic anhydrase; increases NaHCO3
what is thiazide, K+ sparing, loop, mannitol, acetazolamide
carbonic acid generated from carbon dioxide which is produced by normal cellular metabolism; lungs eliminate this acid load by adjusting ventilation while the kidneys regulate nonvolatile acids (not CO2)
what is volatile acid load?
This substance causes mild constriction of the afferent arteriole and strong constriction of the efferent arteriole; this increases total renal vascular resistance which decreases renal blood flow (RBF), maintains or increases GFR at mild-to-moderate activity, decreases GFR at very high levels of activity, increases aldosterone, increases ADH, and increases Na+ reabsorption
what is angiotensin II?
Match the nephron segment with correct description (proximal convoluted tubule, thin descending loop of henle, thin ascending loop of henle, thick ascending loop of henle (TAL), distal convoluted tubule, collecting duct, intercalated cells):
- generates corticomedullary osmotic gradient, reabsorbs 25% of Na+ and is known as the diluting segment; on the apical surface has Na+/K+/2Cl- cotransporter and on the basolateral surface has Na+/K+ ATPase and Cl- channels; high levels of mitochondria because it is major site of ion transport
- main function is Ca2+ reabsorption; the apical surface has Na+/Cl- cotransporters and Ca2+ channels while the basolateral surface has Na+/K+ ATPase, Na+/Ca2+ exchanger, and Ca2+ ATPase; has moderate amount of mitochondria because it is active but less than the PCT or TAL
- bulk reabsorption (65-70% of filtered load) of Na+, water, glucose, amino acids, HCO3-, and phosphate; secretes H+, NH4+, organic acids/bases (drugs); apical surface has Na+/H+ exchanger, SGLT, Na+/amino acid cotransporters while the basolateral surface has Na+/K+ ATPase, GLUT2/GLUT1, and Na+/HCO3- cotransporters; has very high density of mitochondria because it has a high ATP demand for extensive active transport
- dilutes tubular fluid and responsible for passive NaCl reabsorption; there is passive NaCl diffusion and no water permeability; mitochondria levels are very low
- functions in acid base regulation; has high level of mitochondria because active proton pumping requires ATP
- functions in Na+ reabsorption, K+ secretion, and water balance; has aquaporin 2 channel on apical surface and Na+/K+ ATPase and aquaporin 3/4 channels on basolateral surface; moderate amount of mitochondria
- concentrates tubular fluid and has passive water reabsorption; the key transporter is aquaporin 1 since there is no active solute transport; very low amount of mitochondria since passive processes dominate
what is thick ascending loop of henle (TAL), distal convoluted tubule, proximal convoluted tubule, thin ascending loop of henle, intercalated cells, collecting duct, thin descending loop of henle
Match the formula with its definition (filtered load, excreted load, reabsorbed amount, secreted amount):
- filtered load blood pressure - excreted load
- urine concentration x urine flow rate
- excreted load - filtered load
- GFR x plasma concentration of substance
Hormone which inhibits phosphate reabsorption in the PCT thus increasing phosphate excretion via inhibiting Na+/phosphate cotransporters on apical surface and stimulates calcium reabsorption in the distal convoluted tubule via opening TRPV5 Ca2+ channels on apical surface and stimulating Na+/Ca2+ exchanger and Ca2+ ATPase; overall it increases calcium reabsorption, increases plasma calcium, and decreases phosphate levels
parathyroid hormone (PTH)
Line on the Davenport diagram which shows the instantaneous buffering response of blood to changes in PaCO2 (no renal compensation involved); has negative slope because increases in PaCO2 generate H+ that is buffered by non-bicarbonate buffers, causing pH to fall while plasma bicarbonate rises slightly, producing an inverse pH-[HCO3-] relationship
what is the blood buffer line?
- afferent arterioles dilate and efferent arterioles constrict; this increases GFR, increases or maintains RBF, increases filtration fraction, increases Na+ excretion to promote salt and water excretion to reduce volume overload
- afferent arterioles constrict and efferent arterioles dilate; this decreases GFR, decreases RBF, decreases filtration fraction to prevent excessive filtration when tubular flow is too high
- afferent arterioles mildly constrict and efferent arterioles constrict; this maintains or increases GFR at normal levels and decreases GFR at very high levels, decreases RBF, increases filtration fraction
- afferent arterioles dilate; this maintains or increases GFR, increases RBF
- afferent arterioles constrict and efferent arterioles constrict; this decreases GFR, decreases RBF and is seen in shock, hemorrhage, or intense exercise
what is ANP/BNP, adenosine, angiotensin II, prostaglandins (PGE2 and PGI2), norepinephrine
Match the condition with the description (Nephrogenic or central diabetes insipidus)
- dilute urine despite dehydration, dramatic rise in urine osmolality after desmopressin, caused by head trauma or pituitary disease
- dilute urine despite dehydration, no response to desmopressin, caused by hypercalcemia or kidney disease
what is central diabetes insipidus and nephrogenic diabetes insipidus?
The rate at which the kidney excretes or conserves water independent of solute; the formula for this is urine flow rate - osmolar clearance where osmolarity clearance is (urine osmolality x urine flow rate)/plasma osmolality Uosm/Posm; a positive value means free water is being excreted and the urine is dilute while a negative value means free water is being reabsorbed and the urine is concentrated
renin-angiotensin mechanism starting with a decrease in blood pressure
What is decreased blood pressure causes renin release, angiotensin I is converted to angiotensin II by angiotensin converting enzyme (ACE), angiotensin II causes vasoconstriction, efferent arteriole constriction, increased proximal Na+ reabsorption, stimulates aldosterone and ADH, and increases thirst
In high altitudes, peripheral chemoreceptors sense decreased PaO2 stimulating hyperventilation, hyperventilation decreases PaCO2 which leads to decreased carbonic acid and increased pH causing ___; the kidneys compensate for respiratory alkalosis by decreasing H+ secretion, decreasing HCO3- secretion, and increasing urinary bicarbonate excretion
what is respiratory alkalosis?