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SF 3 - Test 3 > 1 - Tubular Reabsorption > Flashcards

1 - Tubular Reabsorption Flashcards

1
Q

Objectives: Explain the major characteristics of transport mechanisms

Diffusion

Facilitated Diffusion

Primary Active Transport

Secondary Active Transport

Endocytosis

A
  • Diffusion
    • Requires electrochemical gradient, “downhill” transport
  • Facilitated Diffusion
    • Requires electrochemical gradient + carriers
    • Thus, exhibits specificity, saturability, and competition; “downhill”
  • Primary Active Transport
    • Requires carriers
    • Thus, exhibitys specificity, saturability, and competition
    • “Uphill” - Requires Energy (ATP)
  • Secondary Active Transport
    • Requires carriers
    • Thus, exhibitys specificity, saturability, and competition
    • Cotransport/Countertransport
      • ​One substance Uphill, One Downhill
  • Endocytosis
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2
Q

Objective: Explain paracellular and transcellular reabsorption

A
  • Paracellular: Diffusion between cells
  • Transcellular: Diffusion across cells
    • Luminal Membrane
    • Basolateral Membrane
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3
Q

Objectives: Explain Tm threshold and splay

A
  • TM = Transport Maximum: Limit to the amounts of material the active transport systems int he renal tubule can transport per unit time
    • Due to saturation of carriers
  • Splay: Appearance of a substance for excretion (in urine) before TM is reached.
    • ​Carrier mediated mechs show enzyme-like kinetics, maximal activity is substrate-dependent
    • Not all nephrons have same Tm for every substance
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4
Q

What are the major physiologic functions of calcium?

A
  • Enzyme cofactors
  • Second messenders
  • Neural transduction
  • Blood clotting
  • Muscle contraction
  • ECM, Cartilage, Bone, Teeth
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5
Q

Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate

Amino Acids

A
  • Major role is conservation; e.g. goal: CAAs = 0
  • Actively Reabsorbed (~ 0 excreted)
    • ​Filtered loads usually <<< TM
      • However, transport mechanisms exhibit considerable splay
  • Several active transporters
  • Even after high protein meal, usually no aminoaciduria
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6
Q

Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate

Organic Nutrients

Citrate

a-Ketoglutarate

B-Hydroxybutyrate

Vitamine C (ascorbic acid)

A
  • Vitamins, metabolic cycle intermediates, etc.
  • Similar characteristics as glucose
  • Citrate: Normal constituent of urine
    • Forms complex with Ca2+, solubilizes it so reduces possibility of kidney stones
  • a-Ketoglutarate: Normal clearance = zero
    • Kidneys don’t regulate; reabsorption is active, high loads used in kidney via Krebs Cycle
  • B-Hydroxybutyrate: Actively reabsorbed, Tm limited
    • ​Excretion is significant at slightly elevated levels, e.g. kidneys regulate body levels of B-hydroxybutyrate
    • Excretion increased in diabetes and starvation
  • Vitamin C: Active reabsorption, Tm limited, marked splay
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7
Q

Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate

Proteins

Why is filtration of protein normall small?

A
  • Glomerulus only filters small amount of protein from blood
  • PT reclaims it by endocytosis, hydrolyzes to amino acids, and releases to ECF via facilitated diffusion
  • Filtration is normally small due to:
    • Steric Hindrance
    • Viscous Drag (lining of pores)
    • Electrical Hindrance, filtration barrier/proteins both negative
  • Kidney ultimately site for catabolism of many plasma proteins, insulin, ANP, bradykinin, etc
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8
Q

Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate

Peptides

What occurs to these in the proximal tubule?

A
  • Small linear polypeptides (e.g. angiotensin II) are completely filterable
  • Catabolized to amino acids within Proximal Tubule by peptidases
    • ​Resulting amino acids are reabsorbed
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9
Q

Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate

Calcium

What effect does PTH have?

A
  • 60% of plasma Ca2+ is filtered across glomerular capillaries
  • Proximal Tubule and Thick Ascending Limb reabsorb > 90% if filtered Ca2+ by passive proccesses coupled to Na+ reabsorption
  • PTH
    • Increases calcium reabsorption by activating adenylate cyclase in distal tubule

***Majority of Calcium is reabsorbed***

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10
Q

Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate

Phosphate

Transport mechanism?

A
  • 90% of plasma phosphate is unbound and freely filtered
  • 90% of this filtered, is actively reabsorbed from nephron
  • Transport Mech: Contransport with Na+, driven by intracellular Na+ gradient
  • Apical: 3Na - 1Pi Symport
  • Basolateral: Pi-Anion Antiporter
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11
Q

What are the three basic renal processes?

A
  • Glomerular Filtration
  • Tubular Secretion
  • Tubular Reabsorption
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12
Q

How is sodium (transport mechanisms) reabsorbed in the cortical collecting duct?

A
  • Lumen to Cytoplasm - Simple Diffusion (Passive)
    • Gradient
  • Cytoplasm to Interstitial Fluid - 1o Active Transport
    • Na, K-ATPase Pump
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13
Q

How is glucose (transport mechanism) reabsorbed in the proximal tube?

A
  • Lumen to Cytoplasm - 2o Active Transport
    • Cotransport w/Sodium
  • Cytoplasm to Interstitial Fluid - Facilitated Diffusion
    • Entire process depends on the Primary Active Na, K-ATPase Pump in basolateral membrane
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14
Q

Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate

Glucose

A
  • Plasma begins to be cleared of glucose as plasma glucose threshold exceeded
  • Filtered Load Increased, and TM-Glucose is reached
  • Glucose begins to appear in urine
    • Plasma Glucose concentration is directly related to clearance of glucose
  • At larger values, reabsorbed glucose becomes small compared to filtered
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15
Q

What is the cause of renal glycosuria? What would TMG be?

How is diabetes mellitus similar?

Pregnancy?

A
  • Renal Glycosuria is glucose in urine, and is result of defective or missing transport mechansim.
  • TMG = 0 (or very low)
  • Diabetes Mellitus: Glucosuria due to lack of insulin, which leads to decreased glucose use in body, and high P[G]
  • Pregnancy: Glucosuria due to increased GFR, glomerular hyperfiltration; RBF may increase 40% from gestational hormones
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17
Q

What is the effect of Thiazide Diueretics on Calcium?

What do these help treat?

A
  • Thiazide Diuretics increase Calcium reabsorption in early distal tubule
  • Result is decrease calcium excretion
  • Treatment plan for idopathic hypercalciuria (high urine calcium)
18
Q

What is the effect of Loop Diuretics? (furosemide)

A
  • Loop Diuretics cause increased urinary calcium excretion
  • Inhibits Na-2Cl-K Cotransporter inhibits the lumen-positive potential difference, and inhibits calcium reabsorption
  • Treatment plan for hypercalcemia (must replace lost volume)
19
Q

What activates PTH (parathyroid hormone)?

What is the result, and how is this facilitated?

A
  • PTH is stimulated by low plasma calcium concentration
  • Action: Increases plasma calcium concentration via bone resorption
  • At high plasma calcium, PTH is supressed and less calcium is reabsorbed
20
Q

What is the result of renal effects on calcium homeostasis?

A

Promotes calcitriol formation in kidney

Increases calcium reabsorption

Increases phosphate excretion

21
Q

What are the three components to total plasma calcium, and how is each component processed by the kidneys?

How does the plasma calcium concentration change with pH?

A
  • Protein Bound (40% - albumin)
    • Does NOT filter
  • Ionized Calcium (50% - Ca2+)
    • ​Active Form, Filters
  • Complexed with Anions (10%)
    • ​Filters
  • Plasma Calcium goes directly with [H+]
22
Q

How do the calcium reabsorption mechanisms change along the kidney pathways?

A
  • Proximal Tubule
    • Paracellular - Driven by solvent drag
    • Transcellular - Enters via ion channel, exit via Ca-ATPase
  • Thick Ascending Limb of Henle’s Loop
    • Paracellular - Driven by electrochemical gradient
  • Distal Tubule
    • Transcellular
      • Enters via ion channels
      • Binds to calbindin, diffuses across cell to basolateral membrane
      • 3Na-1Ca Antiporter, Ca-ATPase
23
Q

What is the physiological importance of phosphate?

A
  • Metabolism (ATP)
  • Hormone Action (cAMP)
  • Tissue Oxygenatio
  • Acid Excretion (renal phosphate buffer)
24
Q

How is phosphate homeostasis accomplished?

A
  • PTH: Inhibits reabsorption of phosphate by proximal tubule
    • ​Stimulates removal of NPT2
  • Dietary Intake: Direct
    • Increase intake, Increase excretion
    • Decreased intake, Decrease excretion

SF 3 - Test 3 (12 decks)

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