Renal Reabsorption Flashcards
Where does filtration take place?
Bowmans capsule
Only about _____ liters of the 150-200 liters of filtrate is excreted as urine, the rest (~ 99%) is reabsorbed into the blood.
1 - 2
Nephrons must reabsorb ~ _____% of the filtrate
99
The proximal convoluted tubule (PCT) reabsorbs ______% of most filtered substances
50-100
The proximal convoluted tubule (PCT) reabsorbs:
Nutritionally important molecules
Solutes by active & passive processes
water by osmosis
small proteins by digestion and/or pinocytosis
________ Transport across the kidney tubule occurs mainly via a variety of channels and transport proteins in the renal tubule cell plasma membranes
Transcellular Transport
Transcellular transport proteins are often exclusively localized to either the _____ or the _____ surface of the tubule cell
apical
basolateral
________ Transport may also occur across the tight junctions between the tubule cells
Paracellular
Paracellular transport will be influenced by the permeability of the _____ _____, limited surface area and the electrical and chemical gradients across the tubule (filtrate versus extracellular fluid)
tight junctions
Where does most Na+ reabsorption take place?
PCT
Sodium Reabsorption in: PCT Ascending Loop DCT Principle cells of late distal tubule and collecting duct
65%
20-30%
5%
1-4%
Principle cells of the late DCT & collecting duct: ~1-4% Na+ reabsorbed (stimulated by ________)
aldosterone (increases blood pressure by increasing water reabsorption)
Aldosterone acts on the cells of the ____ nephron.
distal
Na+ / K+ ATPase pump is localized to the _____ membrane of the nephron epithelial cells
basolateral
Sodium-dependent Secondary Active Transport:
Symport Carriers
Na-glucose (SGLUT & SGLUT1) NA-Amino Acids Na-K-@Cl Na-Cl Na-HCO3-
Sodium-dependent Secondary Active Transport:
Antiport Carriers
Na+-H+ (proximal tubules)
Na+-Ca++
The _____ _______ group of membrane transport proteins has over 300 members organized into 47 families and includes a variety of facilitative transporters and secondary active transporters
Solute Carrier (SLC)
Solute Carrier series does not include members of transport protein families which have previously been classified by other widely accepted nomenclature systems including:
primary active transporters such as ABC (ATP Binding Cassette) transporters
ion channels
aquaporins (water channels)
high H+; low pH
Acidosis
low H+; high pH
Alkalosis
high Na+
Hypernatremia
low Na+
Hyponatremia
high K+
Hyperkalemia
low K+
Hypokalemia
an elevated blood level of the electrolyte sodium usually caused by lack of water (dehydration) or ingestion of massive amounts of salt
Hypernatremia
Hypernatremia symptoms
lethargy, weakness, irritability, and edema
severe elevations of sodium may cause:
seizures, coma and death
hypernatremia may be caused by drugs with _______ activity (______)
mineralocorticoid (cortisol)
a decreased blood level of the electrolyte sodium
Hyponatremia
Symptoms of hyponatremia include:
nausea and vomiting, headache, confusion, lethargy, fatigue, appetite loss, restlessness and irritability, muscle weakness, spasms, or cramps, seizures, decreased consciousness, coma and death
can be caused by excessive water intake or inadequate sodium intake
Hyponatremia
Some medications can accelerate the removal of sodium from the body or increase water retention (hyponatremia):
thiazide diuretics, selective serotonin reuptake inhibitors and some pain medications (accelerate removal of sodium)
desmopressin, MDMA (increase water retention)
Where does most K+ reabsorption take place?
PCT
Potassium Reabsorption:
PCT
Ascending Loop
DCT and Collecting Duct
65%
~20-30%
variable K+ secretion depending on dietary intake
secretion in the DCT & collecting duct is stimulated by _____
aldosterone
is an elevated blood level of the electrolyte potassium
Hyperkalemia
Symptoms of hyperkalemia are fairly nonspecific and generally include malaise, muscle weakness, palpitations and electrocardiographic (ECG) changes such as:
reduction of the size of the P wave
development of peaked T waves
widening of the QRS complex
caused by excessive intake or ineffective elimination of potassium
Renal failure
Mineralocorticoid deficiency
Hyperkalemia
Medications that interferes with urinary excretion of potassium (hyperkalemia)
- ACE inhibitors
- angiotensin receptor blockers
- Potassium-sparing diuretics (amiloride and spironolactone)
- NSAIDs such as: ibuprofen, naproxen, or celecoxib
- calcineurin inhibitor immunosuppressants: (cyclosporin and tacrolimus)
- antibiotics (trimethoprim)
- antiparasitic drugs (pentamidine)
often without symptoms, although it may cause a small elevation of blood pressure and can occasionally provoke cardiac arrhythmias; K+ level >3.0 mEq/L
Mild hypokalemia
may cause muscular weakness, myalgia, muscle cramps, and constipation; K+ level of 2.5-3 mEq/L
Moderate hypokalemia
usually caused by excessive loss of potassium, often associated with vomiting, diarrhea, or excessive perspiration
Hypokalemia
Some medications can accelerate the removal of potassium from the body, including (hypokalemia)
thiazide diuretics, such as hydrochlorothiazide, loop diuretics such as furosemide,
laxatives,
antifungal amphotericin B
Where does most Cl- reabsorption take place?
PCT
Chloride Reabsorption; PCT Ascending Loop DCT Principle cells of late DCT and Collecting Duct
50%
35%
5%
1-4%
Loop (ascending limb)reabsorbs ~35% Cl- via ________________
Na-K-Cl cotransporter
DCT reabsorbs ~5% Cl- via ___________
sodium-chloride symporter
a membrane transport protein that aides in the active cotransport of 1 sodium, 1 potassium, and 2 chloride ions.
The Na-K-Cl cotransporter
There are two isoforms of Na-K-Cl cotransporter:
NKCC1
NKCC2
NKCC1 [Ch5q15-21.1] is widely distributed throughout the body, especially organs that ______fluids
secrete
NKCC2 [Ch5q23.3] is found specifically in the kidney ______ loop
ascending
Na-K-Cl cotransporter is inhibited by _________ & ________
furosamide & bumetanide (loop diuretics)
a symporter ion pump used primarily to remove sodium and chloride ions from the filtrate in the distal convoluted tubule of the kidney
sodium-chloride symporter
sodium-chloride symporter is inhibited by:
thiazide diuretics
Where does most water reabsorption take place?
PCT
_____ is reabsorbed by osmosis and mostly follows sodium
Water
Water Reabsorption: PCT Descending limb DCT Late DCT and Collecting Duct
65%
15%
10-15%
5-10%
Water reabsorption through the late DCT and collecting duct is stimulated by _____. The reabsorption with Na and Cl is stimulated by _______
ADH
Aldosterone
There are ____ Aquaporins in Mammalian Systems
10
_____ Aquaporins in Biological Systems
> 200
AQP 1 is found in: 5
RBC Proximal Tubule Descending loop Brain Astrocytes Supporting cells of Ear
_____ stimulates an increase in water permeability in the renal epithelial cells of the distal tubule & collecting ducts
Vasopressin
water channels
inserted into the
apical membrane
Aquaporin 2
____ hydrostatic pressure and ___ oncotic pressure in peritubular capillaries favors water reabsorption
Low
high
movement of molecules OUT of the tubule filtrate and INTO the peritubular capillary blood
Reabsorption
Proximal tubule apical membrane has increased surface area (_____) which facilitates rapid reabsorption and increased surface area of _____ membrane with mitochondria to produce ATP for active transport
microvilli
basal
_________ _________ important for reabsorption of bicarbonate and secretion of hydrogen ions. This is a diuretic action of ________ ___________ inhibitors
Carbonic anhydrase
Carbonic anhydrase
The proximal convoluted tubule reabsorbs nearly 100% of most nutritionally important molecules such as glucose, amino acids, lactate, succinate, citrate and others via _______ with sodium ions
symport
Glucose is reabsorbed in the proximal convoluted tubule by _____ ______ ______ carriers coupled to Na+
secondary active transport
Transporters can become ________
When transporters reach their maximum transport ability (Tm) no more glucose is reabsorbed
saturated
Glucose concentration in plasma < ___ mg in 100 ml of plasma. Therefore, glucose concentration delivered to the tubules is: ~_____ mg/ min
100
90-110
Transport maximum for glucose = Tm = ~___ mg/min
375
Glucose starts to appear in the urine when plasma concentration is ~____mg/dL
150-200
Renal symporters can not reabsorb glucose fast enough if blood glucose level is above ___ mg/mL.
Some glucose remains in the urine (________)
200
glucosuria
Osmotic action of glucose in the ____ nephron causes an osmotic diuresis (glucosuria)
distal
Common cause of glucosuria is _______ _______ because insulin activity is deficient and blood sugar is too high
genetic disorder produces defect in _____ that reduces its effectiveness
diabetes mellitis
symporter
Na+-K+ ATPase Pump is located in the _______ membrane. Sodium-Glucose Cotransporter (SGLT-2)
is located on the _____ membrane
basolateral
apical
Glucose can be transported ______ (SGLUT), or by _____ diffusion (GLUT)
actively
facilitated
glucose requires ______ transport
mediated
secondary active transport proteins in the membrane of the apical surface
SGLT 1
SGLT 2
responsible for 2% of renal glucose reabsorption and most of intestinal glucose/galactose absorption; on S3 of PCT and intestinal mucosa
SGLT 1
responsible for 98% of renal glucose reabsorption; in S1 and S2 of PCT
SGLT 2
drug used for treatment of type 2 diabetes in adults
The drug is a sodium glucose co-transporter 2 (SGLT2) inhibitor “that blocks the reabsorption of glucose by the kidney, increases glucose excretion, and lowers blood glucose levels”
Dapagliflozin (Farxiga)
SGLT-2 inhibitors, which blocks the reabsorption of glucose by the kidney increasing glucose excretion, and lowering blood glucose levels
Canagliflozin (Invokana)
Dapagliflozin (Farxiga)
Glucose Transporter Proteins facilitated diffusion
GLUT 1 GLUT 2 GLUT 3 GLUT 4 GLUT 5
Broad expression; has high affinity for glucose (not fructose)
in basolateral membrane
GLUT 1
Low affinity for glucose; high capacity transporter (sensor in pancreas)
in basolateral membrane
GLUT 2
glucose transporters in the apical membrane are (secondary active transport)
SGLUT 1 and SGLUT 2
glucose transporters in the basolateral membrane are
facilitated diffusion
GLUT 1 and GLUT 2
___ is located in the basolateral membrane of the EARLY proximal tubule cell
GLUT1
___ is located on the basolateral membrane of the LATE proximal tubule cell
GLUT2
______ is in the apical membrane of the early proximal tubule cell, _____ is in the apical membrane of the Late proximal tubule cell
SGLUT 2, SGLUT 1
Filtered HCO3 is titrated by secreted ___ to CO2 and water
protons
hydration of CO2 in the cell produces protons for secretion and ____, which is transported by _____ cotransporter in a ratio of 3 ___:___Na. Thus one ___ disappears from tubular fluid and another appears in ISF
HCO3-
Na-HCO3
HCO3-1Na
HCO3
a protein (enzyme) in erythrocytes and kidney tubule cells that catalyses the reversible conversion of carbon dioxide and water to carbonic acid
Carbonic anhydrase
A carbonic anhydrase inhibitor
Used to treat some types of glaucoma and conditions of moderate to severe metabolic alkalosis
may be used as a diuretic
will produce bicarbonaturia and type 2 renal tubular acidosis
Acetazolamide
The appearance of protein in the urine (_______) indicates renal pathology
proteinuria
Proteases and peptidases on the apical membrane of the proximal tubule hydrolyze proteins into amino acids that are reabsorbed by
Na+-amino acid transporters (symporters)
Some protein is also taken up by ____ and receptor mediated ______ for digestion by lysosomes or transcellular transport to the basal ECF
pinocytosis
endocytosis
Where do thiazide diuretics inhibit reabsorption
DCT
What protein does thiazide diuretics inhibit?
Na/Cl symporter
Where does furosemide inhibit reabsorption?
Thick ascending limb of Loop
What protein does furosemide inhibit?
Na/K/2Cl cotransporter
