Creatinine, a normal breakdown product of muscle protein creatine, is an endogenous compound that meets the criteria. However, in humans, a small amount of creatinine is secreted into the urine in the proximal tubules. How accurate is it to estimate GFR?
overestimate to GFR slightly
In order for a substance's GFR to be calculated it can only be filtered, not secreted or reabsorbed
In order to estimate renal blood flow, a substance must be freely filtered and completely secreted through tubular secretion
Traits of Para-Aminohippurate (PAH):
freely filtered
at low concentration pI, all PAH escaping filtration is secreted by the tubule
all secreting nephrons of plasma are cleared of PAH
C_PAH = renal plasma flow (blood into kidney)
A person is infused with PAH. After equilibration, plasma PAH is 0.05 mg/mL, urine PAH is 25 mg/mL, and the urine flows 1.5 mL/min. What's the RPF (renal plasma flow) of the person?What's the renal blood flow is the hematocrit is 0.4?
ascending loop of henle = sodium, potassium, chlorine, calcium, bicarbonate
distal tubule = selective absorption of sodium and water and active secretion of ions and acids
collecting duct = sodium, chlorine, urea, water (if ADH)
Reabsorption principles:
sodium is reabsorbed by active transport
electrochemical gradient drives anion reabsorption, partially through aquaporins
concentration of other solutes increases as fluid volume in lumendecreases and permeable solutes are reabsorbed by diffusion
Renal threshold is the plasma concentration at which a specific compound or ion will begin appearing in urine (saturation of mediated transport)
The renal threshold is the x-axis value and the transportmaximum (T_M) is the y-axis value that represents the highest rate it could work
GFR=115 mL/min, T_M for glucose = 287.5 mg/min. Calculate the renal threshold for glucose.
2.5 mg/mL
What's the glucose renal threshold when GFR = 275 mL/min and T_M = 100 mg/min? When her plasma concentration is 15 mg/mL, what's the glucose clearance?
0.36 mg/mL
268 mL/min
Glucose reabsorption occurs primarily in the proximal tubule
Glucose reabsorption:
glucose concentration inside cells is higher than outside because the SGLT uses energy from existing sodium concentration gradient to move glucose against its gradient
glucose diffuses across the basolateral membrane into peritubular capillaries, facilitated by GLUT1/GLUT2
Sodium reabsorption in the proximal tubule:
basolateral side = active transport
apical side = symport, antiport, and leak channels
sodium enters cell through membrane proteins, moving down its gradient
sodium is pumped out the basolateral side through the sodium-potassium ATPase
Sodium-linked active reabsorption in the proximal tubule:
NaHCO3 and sodium solutes are primarily reabsorbed in the first half
co-transport with glucose, amino acids, and organic solutes
counter-transport with hydrogen ions
Sodium-linked active reabsorption in the proximal tubule:
sodium moving down its gradient using SGLT protein pulls glucose into the cell against its concentration gradient
glucose diffuses out of the basolateral side of the cell using the GLUT protein
sodium is pumped out by the sodium-potassium ATPase
Urea passive resorption in proximal tubule:
no active transporters for urea in the proximal tubule
passivereabsorption due to urea concentration gradient
transcellular and paracellular pathways
Protein transcytosis in the proximal tubule:
some small proteins and peptides can pass through the filtration barrier
most filtered proteins are removed from filtrate in the proximal tubule
urea diffuses, plasma proteins use receptor mediated endocytosis (leave through metabolism or exocytosis)
renal digestion of small filtered proteins terminates peptide signals
Proximal tubule secretion:
protons act as the apical Na/H exchanger (NHE)
ammonium ions act as the Na/NH4-antiporter
Na/H-antiporter secretes protons
protons in filtrate combine with filtered bicarbonate to form carbon dioxide
carbon dioxide diffuses into cell and combines with water to form proton and bicarbonate
protons are secreted then excreted
bicarbonate is reabsorbed
glutamine is metabolized to ammonium ion and bicarbonate
NH4 is secreted and excreted
bicarbonate is reabsorbed
Organic compounds are transported across the proximal tubule epithelium primarily by secondary and tertiary active transport with broad specificity
direct active transport = Na/K ATPase keeps intracellular sodium low
secondary indirect active transport = Na/dicarboxylate-transporter (NaDC) moves dicarboxylate inside the cell using energy stored in the sodium concentration gradient
tertiary indirect active transport = the basolateralorganicanion transporter (OAT) concentrates organicanions (OA-) inside the cell using dicarboxylate gradient
organic anions enter lumen by facilitated diffusion
If a person takes both cimetidine (H2 antagonist to treat gastric ulcers) and procainamide (an antiarrhythimc medicine) then both their concentrations will be increased inside the body because they're competing to be excreted
The clearance of penicilin is larger than GFR (F+S)
Loop of Henle Reabsorption:
30% of filtrate reaches here
reabsorbs 15% filtered water and 25% filtered salt, which are not reabsorbed proportionally because the thin and thick ascending have different absorption capacities
the 2 parallel loop of henle segments have different permeabilities
Permeabilities of the parts of the loop of Henle:
thin descending = permeable to water and moderately permeable to urea and ions
thin ascending = impermeable to water and permeable to ions
thick ascending = impermeable to water and ions and actively pumps outsodium and chloride
Distal tubule and collecting ducts reabsorb sodium, chloride (aldosterone sensitive), and water (ADH sensitive)
Distal tubule and collecting duct secrete potassium (aldosterone sensitive), protons (PH dependent), NH4, organic ions, penicilin, and creatinine
potassium exchanges for sodium and protons exchange for potassium in the distal tubule and collecting duct
Acidosis:
type A intercalated discs
extra protons build up in the blood (low pH)
ATPase on the apical side pumps protons into the lumen to be secreted in the urine by bringing protons into the A cell as carbon dioxide (through combination with bicarbonate)
potassium filtered in the lumen is brought into the cell to be reabsorbed into the blood
Alkalosis:
type B intercalated discs
low protons in the blood (high pH)
ATPase in the basolateral side brings in protons, which is made in the cell by taking apart carbon dioxide
chloride is reabsorbed from the lumen, while bicarbonate and potassium are excreted
ADH sensitive water reabsorption (DT and CD):
vasopression binds to membrane receptor
receptor activates cAMP secondary messenger system
cell inserts aquaporins into apical membrane
water is absorbed by osmosis into the blood
Vasopressin (ADH) causes the insertion of water pores called aquaporins into the apical membrane
Vasopressin secretion is stimulated by:
osmolarity greater than 280 mOsm sensed by the hypothalamus
decrease in arterial strech due to decreased blood volume
decrease in blood pressure
Excessive Hydration reaction:
low blood osmolarity (less available solutes)
decreased ADH secretion
removal of water channels from collecting duct
low water reabsorption by osmosis
production of large urine volume
Dehydration reaction:
high blood osmolarity (less available solutes)
increased ADH secretion
insertion of water channels from collecting duct
high water reabsorption by osmosis
production of low urine volume
Aldosterone sensitive sodium reabsorption in distal tubule and collecting duct:
aldosterone combines with cytoplasmic receptor
hormone-receptor complex initiates transcription in nucleus
results in increased sodium reabsorption and potassium secretion
Aldosterone is stimulated by:
decrease in blood pressure (through renin-angiotensin II)
increase in extracellular potassium concentration
increase in potassium concentration stimulates aldosterone secretion to prevent hyperkalemia (leads to cardiac arrhythmias)
increase in potassium plasma concentration causes an increase in aldosterone which causes an increase in potassium tubular secretion in exchange for sodium
The medullary osmotic gradient is established and maintained by the juxtamedullary nephrons and vasa recta and the collecting duct exploits this gradient to form concentrated urine