L27: Proximal Tubule

what substances are reabsorbed by the proximal tubule?

1. glucose

2. water

3. amino acid

4. electrolytes

how does the kidney handle toxins or drugs?

secretion

secretion

active process within epithelial cells; kidney trying to get rid of something with a pump

excretion

the final process of getting rid of urine through muscles to the urethra or ureter to propel urine out

what is the energy in the proximal tubules and why?

high energy consuming segments for reabsorption

basolateral sodium potassium ATPase

main source of energy consumption

where is the proximal tubule located?

primarily in the cortex

SGLT2

sodium glucose transporter

What type of transport process provides energy for reabsorption of glucose?

Secondary active transport

Transcellular

through a cell, no ATP required

Paracellular

btwn cells, no ATP required

secondary active transport

sodium potassium ATPase provides energy for moving glucose up electrochemical gradient

what is the general process for urine processing?

1. filtration

2. reabsorption

3. secretion

where does the ultrafiltrate from the glomerulus travel next?

tubular lumen

where are products from the primary urine reabsorbed?

proximal tubue

what is the order for urine processing transport mechanisms?

1.  Paracellular

2. Transcellular

3. Primary active transport

   mechanisms

4. Secondary active transport

   mechanism

What is an example of a primary active transporter for transporting Na+ and glucose in the proximal tubule?

Na K ATPase

what are the four steps of urine filtration?

1. filtration

2. reabsorption

3. secretion

4. excretion

describe reabsorption in the proximal tubules

“bulk reabsorption.” Iso-osmotic. 2/3 NaCl, H2O. 100% amino acids and glucose

what do we mean when we say iso-osmotic?

same solute concentration in tubule as plasma

loop of henle reabsorption

osmotic pressure gradient; concentrated solutes getting to medulla

distal tubules and collecting ducts have…

regulated absorption dependent on hormones

how much ultrafiltrate is reabsorbed after excretion

99% of the ultrafiltrate is reabsorbed 

how is water reabsorbed in the proximal tubules?

via osmosis

what substances are secreted by the proximal tubules?

1. H+

2. organic acids and bases

3. ammonium ions

4. antibiotics

what is the driving force for the transport processes in the proximal tubule?

Electrochemical gradients and active transport (primary and secondary

describe the process of reabsorption of glucose and amino acids in the proximal tubules

1. Na+/K+ pumps move Na+out of proximal tubule into interstittal fluid to create a sodium gradient via primary active transport

2. Na+ and glucose moved into cell from the filtrate by Na+/glucose SYMPORTERS

3. glucose transported from proximal tubule cell to interstitial fluid via facilitated diffusion to get into peritubular capillary

what is the function of bicarbonate in the proximal tubule?

bind to H+ ions to try and raise pH

how are H+ ions exchanged with Na+ ions in the proximal tubule?

antiporter present on apical membrane of proximal tubule facilitates exchange of ions

why do we want to avoid a very acidic urine?

prevent injury of epithelial tubules lining urinary tract

how is ammonia created in the proximal tubules and what is the funciton?

proximal tubule cells break down glutamine to create ammonia which can then be secreted to bond to H+ ions, helping to regulate pH levels

how is glutamine broken down into ammonia?

1. H+ from plasma binds ammonia

2. Ammonium exchanged for Na+

3. ammonium obligates Cl- secretion

4. α-ketoglutarate enters Krebs cycle and produces bicarbonate

5. bicarbonate is reabsorbed with Na+HCO3 exchanger

How does the Na+ - H+ antiport mechanism contribute to secretion of H+ in the proximal convoluted tubule?

it transports Na+ into the cell and H+ out of the cell

How does glutamine contribute to bicarbonate reabsorption in the proximal tubule?

Glutamine is metabolized to produce ammonium and bicarbonate, with bicarbonate reabsorbed

into the blood

where is ionized calcium filtered?

glomerulus

where is majority of free calcium reabsorbed?

proximal tubule

what is the  passive movement of calcium between proximal tubule cells is driven by?

the active transcellular reabsorption of sodium, which provides the driving force for the osmotic reabsorption of water

how does the reabsorption of calcium predominantly occur?

paracellular pathway by solvent drag

where does the small amount of transcellular calcium reabsorption occur?

straight portion of the proximal tubule

what controls the transcellular calcium reabsortption?

mediated by a voltage-gated calcium channel and sensitive to hormones

the reabsoprtion of phosphate in the proximal tubule is exclusively…

a transcellular processinvolving sodium-phosphate cotransporters.

describe phosphate entry into proximal tubule

apical phosphate entry is driven by the inward gradient for sodium, which is maintained by the activity of the basolateral Na+K+ATPase

how does PTH inhibit proximal tubular phosphate reabsorption?

 by decreasing the apical membrane expression of sodium-phosphate transporters

what triggers the release of PTH?

1. hypocalcemia

2. hyperphospotemia

what conditions does the body prefer to get ATP for excretion in the kidneys?

aerobic conditions

how does dehydration influence excretion?

decreased oxygen in plasma = decreased GFR = increased waste products remain

where is vitamin D made?

in the kidneys

what hormone will compensate for the change of ionized calcium plasma concentration in hyperphosphotemia?

PTH

where is reabsorption of filtered magnesium taking place?

• main= thick ascending limb (50-70%)

• some in proximal tubule (10-25%)

how does reabsorption of magnesium occur in the proximal tubules?

by a passive paracellular mechanism that is likely to be largely unregulated.

reabsorption of uric acid

first half of the proximal tube reabsorbs uric acid, but the final part secrets it

which breed suffers from a genetic disorder that limits their capacity to transport uric acid from the blood to the liver (allantoin) and from the renal tubular lumen to the blood (absorption)?

dalmatians

what happens with dalmatians that have genetic disorder of transporting uric acid?

uric acid concentration increases (high filtration and low reabsorption) in the tubular lumen and

dalmatians subsequently in the urine

obligatory reabsoprtion of water

occurs in the proximal tubule, where approximately 65-70% of filtered water is reabsorbed, following osmotic gradients; NOT DEPENDENT ON HORMONES

how is water reabsorbed into proximal tubule?

1. solutes follow passive diffusion or active transport to get into tubule cell and interstitial fluid

2. solute concentration gradient draws water into tubule via osmosis

what products are secreted in the proximal tubule?

1. hydrogen

2. waste products

3. drugs

fanconi syndrome

A disorder affecting the proximal tubule's ability to reabsorb substances such as glucose, bicarbonate, and amino acids, resulting in their loss in urine.

what breed suffers from fanconi syndrome?

basenji’s

whaat can lead to fanconi syndrome?

1. chicken jerky treat ingestion

2. gentamicin nephrotoxicosis

3. idiopathic form

what is the transport mechanism for sodium in the proximal tubule?

primary active (Na+ K+ ATPase)

what is the transport mechanism for ammonium in the proximal tubule?

Na+ ammonium exchanger

what is the transport mechanism for H+ in the proximal tubule?

Na+ / H+ antiporter/exchanger

what is the transport mechanism for glucose and amino acids in the proximal tubule?

Na+ glucose symporter via secondary active Na + / K+ ATPase

what is the transport mechanism for iCa2+ in the proximal tubule?

paracellular promoted by Na+ / K+ ATPase

what is the transport mechanism for phosphate in the proximal tubule?

Na+/ phosphate cotransporter by secondary active Na+ / K+ ATPase