1 - Tubular Reabsorption Flashcards
Objectives: Explain the major characteristics of transport mechanisms
Diffusion
Facilitated Diffusion
Primary Active Transport
Secondary Active Transport
Endocytosis
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Diffusion
- Requires electrochemical gradient, “downhill” transport
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Facilitated Diffusion
- Requires electrochemical gradient + carriers
- Thus, exhibits specificity, saturability, and competition; “downhill”
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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
Objective: Explain paracellular and transcellular reabsorption
- Paracellular: Diffusion between cells
- Transcellular: Diffusion across cells
- Luminal Membrane
- Basolateral Membrane
Objectives: Explain Tm threshold and splay
-
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
What are the major physiologic functions of calcium?
- Enzyme cofactors
- Second messenders
- Neural transduction
- Blood clotting
- Muscle contraction
- ECM, Cartilage, Bone, Teeth
Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate
Amino Acids
- Major role is conservation; e.g. goal: CAAs = 0
-
Actively Reabsorbed (~ 0 excreted)
-
Filtered loads usually <<< TM
- However, transport mechanisms exhibit considerable splay
-
Filtered loads usually <<< TM
- Several active transporters
- Even after high protein meal, usually no aminoaciduria
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)
- 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
Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate
Proteins
Why is filtration of protein normall small?
- 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
Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate
Peptides
What occurs to these in the proximal tubule?
- Small linear polypeptides (e.g. angiotensin II) are completely filterable
-
Catabolized to amino acids within Proximal Tubule by peptidases
- Resulting amino acids are reabsorbed
Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate
Calcium
What effect does PTH have?
- 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***
Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate
Phosphate
Transport mechanism?
- 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
What are the three basic renal processes?
- Glomerular Filtration
- Tubular Secretion
- Tubular Reabsorption
How is sodium (transport mechanisms) reabsorbed in the cortical collecting duct?
- Lumen to Cytoplasm - Simple Diffusion (Passive)
- Gradient
- Cytoplasm to Interstitial Fluid - 1o Active Transport
- Na, K-ATPase Pump
How is glucose (transport mechanism) reabsorbed in the proximal tube?
- 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
Objectives: Explain the kidney handing of glucose, amino acids, proteins, organic nutrients, calcium, and phosphate
Glucose
- 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
What is the cause of renal glycosuria? What would TMG be?
How is diabetes mellitus similar?
Pregnancy?
- 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
