B&B Renal: Nephron Physiology Flashcards
Reabsorbed substances
- H2O
- NaCl
- K+
- HCO3-
- Glucose
- Amino acids
Diffusion
Reabsorption
[U] > [P]
* Diffusion from urine to blood through cells via channels
* Paracellular diffusion between cells
Osmotic diffusion
Reabsorption
Urine [mOsm] < Plasma [mOsm]
* Water reabsorption via osmosis either through cells or paracellularly
Segments of nephron
Histology
- Proximal tubule
- Descending limb
- Ascending limb
- Distal tubule
- Collecting duct
Proximal tubule
Reabsorption
- Complete reabsorption (100%):
- Glucose
- Amino acids
- Partial reabsorption (67%):
- Water
- HCO3-
- NaCl
- K+
- PO4-
Na/K-ATPase pump
Proximal Tubule
- Located in BL membrane
- Uses ATP to pump Na+ out of cells into blood
* Creates low [Na] in proximal tubule cells
* Cells use low [Na] as driving force to reabsorb solutes & H2O - K+ is pumped into cells from blood
- Creates high [K] in proximal tubule cells
BL = basolateral
Proximal tubule transporters
Reabsorption
- Glucose transporters
- SGLT2: uses [Na] gradient to cotransport glucose across apical membrane into cells
- GLUT1/2: facilitated diffusion of glucose across BL membrane into blood
- Cl-/K+ symporter: BL membrane
- Uses [K] gradient to cotransport K+ & Cl- into blood
- Cl- anion exchanger: apical membrane
- Links Cl- reabsorption to excretion of anions into urine
- Anions: OH-, formate, oxalate, sulfate
- Na+/H+ exchanger: apical membrane
- Cotransports Na+ into cells & H+ into urine
SGLT: sodium-glucose linked transporter; GLUT = glucose transporter
Glucose
Reabsorption
Completely reabsorbed in proximal tubule
* SGLT2: Na/glucose symporter
* Serum glucose: 160 mg/dL –> glycosuria
* Glucose: 300 mg/dL –> all SGLT2 saturated
* Any further increase in serum glucose will be excreted in the urine
* Diabetes mellitus = “sweet” diabetes
* Diabetics have sweet urine
Amino acids
Reabsorption
Completely reabsorbed in proximal tubule
* Na/AA cotransporters
* Hartnup disease
* No tryptophan transporter in PCT
* Tryptophan deficiency –> niacin deficiency
* Presentation:
* Skin rash resembling pellagra (plaques, desquamation)
* Amino acids in urine
Bicarbonate (HCO3-)
Proximal Tubule
- Na/H+ exchanger: apical membrane; cotransports Na into cells & H+ into urine
- H+ combines with HCO3- to form H2CO3
- Luminal CA: converts H2CO3 to CO2 & H2O
- CO2 & H20 diffuse into cells from urine
- Cytoplasmic CA: converts CO2 & H2O to H2CO3
- H2CO3 breaks down into H+ & HCO3-
- NBC: BL membrnae; cotransports Na & HCO3- from cells into blood
- H+ is recycled & progress repeats
- Result: Na+ & HCO3- reabsorbed; H+ secreted
CA: carbonic anhydrase; NBC: sodium bicarbonate cotransporter
Bicarbonate reabsorption
Clinical Correlations
- Carbonic anhydrase inhibitors
- Inhibit bicarcbonate reabsorption
- Weak diuretics: inhibit Na-linked uptake
- Type II renal tubular acidosis
- Ion defect; inability to absorb bicarbonate
- Metabolic acidosis
Fanconi syndrome
Proximal Tubule
Loss of proximal tubule functions
* Impaired resorption of solutes
* Loss of HCO3-, glucose, amino acids, phosphate, low MW proteins
Loss of proximal tubule functions
* Impaired resorption of solutes
* Loss of HCO3-, glucose, amino acids, phosphate, low MW proteins
Pathophysiology
Fanconi syndrome
- Polyuria, polydipsia
- Non-anion gap acidosis
- Hypokalemia
- Hypophosphatemia
- Amino acids in urine
Presentation
Fanconi syndrome
- Polyuria, polydipsia
- Osmotic diuresis due to glucose
- Normal serum glucose: contrast with DM
- Non-anion gap acidosis
- Acidosis due to loss of HCO3-
- Hypokalemia
- Increased nephron flow & loss of K+
- Hypophosphatemia
- Increased nephron flow & loss of PO4
Fanconi syndrome
Epidemiology
- Inherited or acquired syndrome (rare)
- Inherited form associated with cystinosis
- Lysosomal storage disease
- Results in accumulation of cystine
- Presents in infancy with Fanconi syndrome
- PCT = initial site of cystine buildup