B&B Renal: Nephron Physiology Flashcards

1
Q

Reabsorbed substances

A
  1. H2O
  2. NaCl
  3. K+
  4. HCO3-
  5. Glucose
  6. Amino acids
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2
Q

Diffusion

Reabsorption

A

[U] > [P]
* Diffusion from urine to blood through cells via channels
* Paracellular diffusion between cells

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3
Q

Osmotic diffusion

Reabsorption

A

Urine [mOsm] < Plasma [mOsm]
* Water reabsorption via osmosis either through cells or paracellularly

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4
Q

Segments of nephron

Histology

A
  1. Proximal tubule
  2. Descending limb
  3. Ascending limb
  4. Distal tubule
  5. Collecting duct
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5
Q

Proximal tubule

Reabsorption

A
  • Complete reabsorption (100%):
    • Glucose
    • Amino acids
  • Partial reabsorption (67%):
    • Water
    • HCO3-
    • NaCl
    • K+
    • PO4-
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6
Q

Na/K-ATPase pump

Proximal Tubule

A
  • 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

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7
Q

Proximal tubule transporters

Reabsorption

A
  • 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

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8
Q

Glucose

Reabsorption

A

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

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9
Q

Amino acids

Reabsorption

A

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

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10
Q

Bicarbonate (HCO3-)

Proximal Tubule

A
  • 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

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11
Q

Bicarbonate reabsorption

Clinical Correlations

A
  • 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
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12
Q

Fanconi syndrome

Proximal Tubule

A

Loss of proximal tubule functions
* Impaired resorption of solutes
* Loss of HCO3-, glucose, amino acids, phosphate, low MW proteins

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12
Q

Loss of proximal tubule functions
* Impaired resorption of solutes
* Loss of HCO3-, glucose, amino acids, phosphate, low MW proteins

Pathophysiology

A

Fanconi syndrome

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13
Q
  • Polyuria, polydipsia
  • Non-anion gap acidosis
  • Hypokalemia
  • Hypophosphatemia
  • Amino acids in urine

Presentation

A

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

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14
Q

Fanconi syndrome

Epidemiology

A
  • 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
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15
Q

Fanconi syndrome

Acquired Causes

A
  • Lead poisoning
  • Multiple myeloma
  • Drugs
    • Cisplatin (CTX)
    • Ifosfamide (alkylating agent)
    • Tenofovir (HIV drug)
    • Valproate
    • Aminoglycoside antibiotics
    • Deferasirox (iron chelator)
16
Q

Thin Descending Limb (TDL)

Loop of Henle

A

Permeable to H2O; impermeable to NaCl
* Hypertonicity of medulla draws water from urine
* Osmotic diffusion
* Water leaves urine & leaves NaCl behind
* Concentrates urine
* Dilute urine enters descending limb: 300 mOsm/L
* Concentrated urine leaves: 1200 mOsm/L

17
Q

Osmolarity of nephron

Reabsorption

A
  • Cortex: 300 mOsm/L
  • Outer medulla: 600 mOsm/L
  • Inner medulla: 1200 mOsm/L
18
Q

Osmolar gradient

Osmolarity of Nephron

A
  • Solutes that maintain gradient: Na, Cl, Urea
  • Urea is generated by liver & protein metabolism
    • Reabsorbed by collecting duct
      • High permeability to urea
    • Essential to maintaining gradients
      • Resorbed urea accumulates in medullary interstitium
19
Q

Thick Ascending Limb (TAL)

Loop of Henle

A

Permeable to NaCl; impermeable to H2O
* NaCl is resorbed from urine
* NaCl resorption pulls solutes out of urine
* Dilutes urine
* Dilute urine leaves ascending limb: 120 mOsm/L

20
Q

Thick ascending limb transporters

Loop of Henle

A
  • Na/K-ATPase pump: BL membrane
    • Uses ATP to pump Na+ into blood & cotransport K+ into cells
      * Creates low [Na] & high [K] in cells
  • NKCC: apical membrane
    • Uses [Na] gradient to cotransport Na+, K+, and 2 Cl- from urine into cells
  • K+ channel: apical membrane
    • Some K+ diffuses out of cells into urine down its concentration gradient
    • Increased [K] in urine creates positive charge, which drives reabsorption of Mg2+, Ca2+ from urine via paracellular diffusion

NKCC: Na-K-Cl cotransporter

21
Q

Distal tubule transporters

Reabsorption

A

Na+, Cl- , Ca2+ reabsorption
* Na/K-ATPase pump: BL membrane
* Uses ATP to pump Na+ into blood & cotransport K+ into cells
* Creates low [Na] & high [K] in cells
* NCC: apical membrane
* Uses [Na] gradient to cotransport Na & Cl from urine into cells
* Cl- channel: BL membrane
* Cl- diffuses across channels into blood
* Ca2+ channel: apical membrane
* Diffusion of Ca2+ from urine into cells
* Na+/Ca2+ exchanger: BL membrane
* Uses [Ca] to cotransport Na+ into cells & Ca2+ into blood

NCC: Na/Cl cotransporter

22
Q

Principal cell transporters

Collecting Duct

A

Na+ & H2O reabsorption; K+ secretion
* * Na/K-ATPase pump: BL membrane
* Uses ATP to pump Na+ into blood & cotransport K+ into cells
* Creates low [Na] & high [K] in cells
* ENaC: apical membrane
* Facilitated diffusion of Na+ into cells
* Na+ reabsorption
* K+ channels: apical membrane
* Facilitated diffusion of K+ into urine
* K+ secretion
* AQP-2: apical membrane
* Increase membrane permeability to H2O
* H2O diffuses into cells following Na+

ENaC: epithelial Na+ channel; AQP-2: aquaporin-2

23
Q

Intercalated cell transporters

Collecting Duct

A

H+ secretion
* H+-ATPase: apical membrane; uses ATP to pump H+ from cells into urine

24
Q

Collecting Duct (CD)

Functions

A
  • Reabsorption: Na+, H2O, urea
    • Na: depends on aldosterone
    • H2O: depends on ADH
    • Urea: depends on ADH
  • Secretion: K+, H+
    • Increased Na+ delivery –> increased K+ excretion
      • Contributes to hypokalemia with loop & thiazide diuretics
    • Depends on aldosterone
25
Q

Aldosterone

Collecting Duct Hormones

A
  • Steroid (mineralocorticoid) hormone
    • Promotes gene expression
  • Upregulates: Na/K-ATPases, ENaC channels
    • Promotes Na+ & H2O resorption
      * Increases ECV
    • Promotes K+ secretion principal cells
    • Promotes H+ secretion intercalated cells
  • Aldosterone release is stimulated by:
    • Ang II (RAAS)
    • Hyperkalemia
    • ACTH (minor effect)
26
Q

Nephron water permeability

H2O Reabsorption

A
  • Permeable: proximal tubule, TDL
  • Impermeable: TAL, distal tubule
  • Variable: collecting duct
27
Q

ADH

Collecting Duct Hormones

A
  • Promotes free water retention
    • Increases water resorption from urine
  • Two ADH receptors:
    • V1: vasoconstriction
    • V2: antidiuretic response
  • Released from posterior pituitary is stimulated by:
    • Hyperosmolarity: physiologic stimulus
    • Volume loss: non-osmotic release
28
Q

ADH water resorption

Collecting Duct Hormones

A
  • V2 receptors: located in CD principal cells
    • GPCR; cAMP 2nd messenger system
  • Activation of receptor induces endosome insertion into cell membrane
    • Endosomes contain aquaporin-2
  • Result: increased water permeability
    • CD can be completely permeable / impermeable to water depending on presence of ADH & AQP-2
29
Q

ADH & urea

A
  • Urea = key osmole in kidney
  • Medullary CD is permeable to urea
    - ADH increases urea reabsorption
  • Urea enters medullary interstitium & forms osmotic gradient
    - Urea is recycled in TDL: transporters return urea from interstitium into urine for excretion