Reabsorption/Secretion in the Proximal Tubule Flashcards
What are the main waste products excreted by the kidney?
• How much is REABSORBED?
- Urea
- Creatinine
- Uric Acid
***Filtering this out ~60 times a day keeps things clean
2/3 of glomerular Filtrate is Reabsorbed in the Proximal Tubule*** this includes water and solutes
How many times per day is the entire body fluid turned over?
• why is this necessary?
5 times daily
• Essential to Maintain ECFV, Electrolytes, and Solutes in Glomerular Filtrate
What major process takes place in the proximal tubule?
- Filtration = Glomerulus
- Reabsorption = Proximal Tubule
- Secretion = Distal Tubule
What formula is used to determine rate of flow into the loop on henle?
V = (GFR x Ps) / TFs
V = rate of flow into Loop of Henle Ps = Plasma Concentration of Substance TFs = Tubule Fluid Concentration of Substance
How do you use the rate of flow of fluid into the loop of henle to determine the amount of Resorption occurring?
Resorption = Starting Flow. - V
V = rate of flow into L.O.H.
What processes allow for isotonic reabsorption in the proximal tubule?
Reabsorption:
• Sodium
• Chloride
• Bicarbonate
How can reabsorption of solutes in the proximal tubule like Na+, HCO3-, Cl- occur without a change in filtrate osmolarity?
• how is this different from inulin?
- Water Follows these 3 major solutes that are reabsorbed so overall concentration is not reduced but FLUID AMT. IS reduced
- Inulin is NOT reabsorbed so as you move down its concentration just stays the same
Sodium Transport in Proximal Tubule: • Active or Passive? • Driving Forces? • How do these arise? • Describe Luminal and Apical transport
ACTIVE TRANSPORT:
• Drives sodium movement
DRIVING FORCES:
• Depends on DECREASED [Na+] and…
• INCREASED membrane (-) membrane potential
Creation of Gradient:
BASOLATERAL Na+/K+ = Key driving forces:
• is ATP dependent
REABSORPTION OF Na+:
LUMINAL channels are responsible for getting Na+ into tubular cells
What are some of the molecules that get co-transported with Na+/ what are the transporters called?
- Na+ - H+ exchanger
- Na+ - Glucose co-transport
- Na+ Amino Acid co-transport
- Na+ - Phosphate co-tranporter
- Claudin-2 in Tight juntions = another transporter
What is sodium Reabsorption always accompanied by?
• how is this accomplished?
- ANION reabsorption - specifically Cl- and HCO3-
* Na+ movement to interstitium generates -5mV gradient and LEAKY EPITHELIUM of proximal tubule and potassium follows
How does Chloride move across the proximal tubule?
• Claudin 4 (Cldn 4) IN TIGHT JUNCTIONS allows Cl- to pass PARACELLULARLY
How does the rate Chloride reabsorption compare to Bicarbonate reabsorption in the proximal tubule?
• why is this the case?
- Chloride Reabsorption occurs more slowly because it just uses the -5mV gradient and Claudin-4 to move Paracellularly
- HCO3- uses ACTIVE transport to move across lumen so its MORE RAPIDLY absorbed in Proximal tubule
T or F: bicarbonate just neutralized so that it can move across luminal cells.
FALSE, this is ACTIVE transport, not just neutralization
**Describe the Method by which bicarbonate is reabsorbed.
- H2O and CO2 come together to make H2CO3 via Intracellular Carbonic Anhydrase
- H2CO3 dissociates into H+ and HCO3-
Following HCO3- => INTERSTIUM
a. 3 HCO3- can be transferred to INTERSTITIUM via HCO3-/Na+ exchanger
Following Hydrogen => LUMEN
a. H+ is exported via hydrogen channel? or Na+/H+ exchanger
b. This lumenal H+ combines with HCO3- in the LUMEN to make H2CO3
c. H2CO3 dissociates into H2O and CO2
How is water Reabsorbed?
LEAKY Epithelium with Lots of AQUAPORINS = HIGH Kf (high hydraulic conductivity)
What are the aquaporins that are responsible for absorption of H2O in the proximal tubule?
• what about elsewhere in the nephron?
PROXIMAL TUBULE:
•AQP-1 - Apical side of cell
• AQP-4/5 Basolateral membrane
DISTAL TUBULE:
• AQP - 2 - regulated by vasopressin
What Factors drive H2O uptake INTO CAPILLARIES from interstitial Fluid?
- POSITIVE PRESSURE of INTERSITIAL FLUID
- LOW hydrostatic pressure in the capillary
• because of pressure drop across afferent and efferent arterioles - HIGH ONCOTIC pressure in peritubular capillary
• because of glomerular filtration and retention of proteins
Why does inulin increase to 3 times the concentration in the glomerular capillaries by the time it gets to the Loop of Henle?
because it is not reabsorbed so Amt. stays the same but the water volume is decreased to 1/3 of the orginal vol.
***This means concentration is increased by 3.
How is glucose transported across the proximal tubule?
• what is Threshold?
• what is Tm?
Sodium-Glucose co-transporter (SGLT1 and 2)
• couple glucose transport to the Na+ gradient
Threshold:
• at 200-220 mg/dL some nephrons become saturated with glucose and you START TO SEE GLUCOSE IN THE URINE
Tm:
• ALL nephrons are maxed out and GLUCOSE INCREASES IN THE URINE ARE PROPORTIONAL TO PLASMA GLUCOSE
What are some physiologic and pathologic causes of Glucosuria?
Physiologic:
• Pregnancy
Pathologic:
• DIABETES MELLITUS
• FAMILIAL RENAL GLUCOSURIA MUTATION IN SGLT1/2
Describe the absorption of amino acids and organic acids in the proximal tubule of the kidney?
• where do most organic acids come from?
Amino Acids:
• Co-transport with Na+
• only 0.5-2% excreted
Organic Acids:
• Co-transport with Na+
• Most organic acids come from Krebs Cycle intermediates
What are some diseases where ORGANIC acid secretion is hight?
Organic Acids:
• High in DIABETIC KETOACIDOSIS
T or F: there are many transporters to reabsob peptides.
True, very little peptide should ever be excreted in the urine
What are some diseases that cause Proteinuria?
- Multiple Sclerosis
- Hemoglobinemia
- Myoglobinemia
T or F: like glucose, phosphates have a fixed transport maximum.
FALSE, PTH controls the transport maximum for phosphate
Why is phosphate often excreted rather than reabsorbed?
• what causes changes in this?
• Transport mechanism when resorption is used?
Phosphate:
• Important buffer in the blood so we need to keep it at a constant concentration
Changes:
• PTH secreted by the pituitary controls this
Mechanism:
• Na+ cotransport is used when reabsorption is done
While 66% of fluid is reabsorbed in the proximal tubule, only 60% of Cl- is reabsorbed. why?
Cl- must compete with ACTIVELY transported HCO3-
How is urea reabsorbed?
*what would be an easy way to increase urea excretion?
Urea is PASSIVELY reabsorbed in the PT
• this is SLOW so a greater URINARY FLOW would DECREASE urea absorption
**Typically only 50% reabsorbed
What is the use of substances that are FREELY FILTERED but not rapidly reabsorbed?
• example?
DIURESIS:
• MANNITOL - will increase osmolarity of filtrate so less H2O leaves tubule and more gets excreted
CLINICAL USE:
• Reduction of Intracranial Pressure, Intraocular Pressure, promotes excretion of toxins and edema