Renal Lecture 2 Flashcards
Topic 4: The Renal System
Glomerular Filtration
Passive, nonselective; driven by capillary pressure
Efficient due to:
1000x more permeable membrane
Higher blood pressure (55 mm Hg vs. < 26 mm Hg)
180 L filtrate in kidneys vs. 2-4 L in other cap beds.
watch the video
Filtration Membrane Anatomy
- btw blood and interior of glomerular capsule
3 layers:
Fenestrated capillary endothelium
Basement membrane
Visceral membrane (podocyte foot processes)
Fenestrated Capillary Endothelium: Allows small molecules and water to pass while blocking blood cells.
Basement Membrane: Prevents larger proteins and molecules from passing.
Visceral Membrane (Podocyte Foot Processes): Filters out large proteins through slit diaphragms.
If the glomerular capillary is damaged, large molecules such as proteins can pass through the filtration membrane and appear in the urine.
The filtration membrane components are only found in the glomerulus, not in the PCT, DCT, loop of Henle, or collecting ducts, which are involved in reabsorption and secretion instead of filtration.
Filtration Summary
Molecules < 3 nm pass easily
Molecules 3-5 nm pass with difficulty
Molecules > 5 nm are not filtered
Negative charge on basement membrane limits larger proteins
Retained plasma proteins maintain osmotic pressure
Proteins/RBCs in urine indicate membrane damage
HPg – pushes out of blood (glomerular blood hydrostatic pressure
OPg – pulls back into blood (blood colloid osmotic pressure) HPc – pushes back into blood (capsular hydrostatic pressure)
Opg - like water.
HPc: associated with the lumen of glomerulus lumen.
ex: pressure responsible for filtrate formation
NFP = HPg (outward pressure) – (OPg + HPc) - inward pressure
Glomerular Filtration Rate (GFR)
Filtrate formed per minute (~125 ml/min)
Depends on:
Filtration surface area
Membrane permeability
Net filtration pressure (NFP)
Large surface area = large filtrate despite low NFP
15% decrease in BP stops filtration
GFR ↑ with BP, ↓ with dehydration
Filtration surface area: Can be affected by kidney diseases or damage to glomeruli.
Membrane permeability: Can be influenced by factors like inflammation, disease states, or injury.
Net filtration pressure (NFP): Can change with factors like blood pressure, hydration, or kidney health.
GFR (125 ml/min) is standard.
Kidney surface area = equivalent to skin; damage affects filtration.
Chronic high BP: Can damage kidneys, but exercise helps.
Low BP/dehydration: BP < 55 mm Hg stops filtration, leading to kidney failure.
3 Regulatory Influences on GFR
Renal Autoregulation (Intrinsic)
Maintains constant GFR by adjusting nephron blood flow.
Primarily regulates afferent arteriole.
2 mechanisms:
Myogenic
Tubuloglomerular feedback
Neural Controls (Extrinsic)
Sympathetic nervous system regulates GFR during stress/low BP.
Renin-Angiotensin System (Extrinsic)
Activated by low BP or sodium, adjusts kidney blood flow. increases GFR through vasoconstriction and sodium/water retention.
Importance:
Maintains stable GFR despite external changes.
Target:
Afferent arteriole for blood flow regulation.
1a) Myogenic Mechanism:
Responds to BP changes in afferent arteriole.
High BP: Contraction (reduces blood flow).
Low BP: Relaxation (increases blood flow).
1b) Tubuloglomerular Feedback Mechanism:
Macula densa cells monitor NaCl levels.
High NaCl: Release vasoconstrictors (e.g., ATP).
Low NaCl: Release less ATP, allowing vasodilation.
Autoregulation keeps GFR constant (80-180 mm Hg).
Below 80 mm Hg: Autoregulation stops, extrinsic regulation takes over.
Watch the videos
- Extrinsic Mechanisms:
2a. Neural Controls
SNS activates under stress, overriding autoregulation.
Blood is redirected to heart, brain, muscles.
Vasoconstriction of afferent arterioles.
2b. Renin-Angiotensin Mechanism
Renin release triggers:
SNS stimulation.
Macula densa detects low osmolarity/flow.
Reduced stretch of granular cells.
ACE is in lung capillaries.
Renin-Angiotensin System
Angiotensinogen → Renin → Angiotensin I → Angiotensin II (via ACE).
Angiotensin II: Potent vasoconstrictor.
Stimulates aldosterone release, increasing Na+ reabsorption and water retention, raising BP.
Effect on Glomerular BP/Filtration Rate:
Fewer receptors on afferent arterioles → vasoconstriction of efferent arterioles → increased glomerular BP and filtration rate.
Main Purpose:
Stabilizes blood pressure and ECF volume.
(A) Myogenic Mechanism:
High BP → GFR rises → Afferent arteriole constricts → Blood flow & GFR return to normal.
(B) Tubuloglomerular Feedback:
High BP → GFR rises → Macula densa releases vasoconstrictors → Blood flow & GFR return to normal.
(C) Nervous System Regulation:
Low BP → Sympathetic activity increases → Vasoconstriction → GFR decreases → Urine volume decreases → BP rises.
(i) Myogenic Mechanism:
Decreased BP → Lower blood flow in afferent arterioles → Less stretch of smooth muscle → Vasodilation of afferent arterioles → Increase in GFR.
(ii) Tubuloglomerular Feedback:
Decreased BP → Lower GFR → Reduced filtrate flow and NaCl in nephron → Macula densa cells release vasoconstrictors → Vasodilation of afferent arterioles → Increase in GFR.
(iii) Hormonal (Renin-Angiotensin-Aldosterone) Mechanism:
Decreased BP → Renin release from granular cells → Angiotensin II → Increased aldosterone secretion → Na+ reabsorption (increases blood volume) or vasoconstriction → Increased BP.
(iv) Neural Controls:
Decreased BP → Baroreceptor inhibition → Sympathetic activation → Vasoconstriction of renal afferent arterioles → Decreased GFR.
Intrinsic Mechanisms (Myogenic & Tubuloglomerular) directly regulate GFR despite moderate BP changes (80-180 mm Hg).
Extrinsic Mechanisms (Hormonal & Neural) indirectly regulate GFR by maintaining systemic BP, which drives kidney filtration.
Importance of Tubular Reabsorption
45 min: Total blood volume filtered by kidneys; most of it is reabsorbed, not excreted as urine.
Reabsorption mainly occurs through cells, not between them.
Reabsorption Principles:
Organic nutrients (glucose, amino acids) are 100% reabsorbed.
Reabsorption can be active (using energy) or passive (without energy).
Water/ion reabsorption is hormonally regulated.
Process Details:
In filtrate:
Glucose, amino acids, Na+, vitamins: Secondary active transport (via transport proteins).
Lipid-soluble substances, ions, urea: Passive transport (diffusion via aquaporins).
Tubule cells:
Active transport (Na+/K+ pump).
Water: Passive transport via aquaporins.
In interstitial fluid:
Na+, K+, urea: Diffuse into bloodstream via paracellular route.
Active vs Passive Reabsorption:
Active Reabsorption: Moves substances against gradients using ATP (e.g., Na+).
2o Active Transport (linked to Na+): Glucose, amino acids, lactate, vitamins.
Transport Max (Tm): When carriers are saturated, excess appears in urine (e.g., glucose in diabetes).
Passive Reabsorption: Substances move down their concentration gradient (e.g., diffusion, aquaporins for water).
Substances like K+, H+, drugs are secreted into filtrate for excretion. check
3 Substances Not Reabsorbed & Why:
Creatinine: Waste product to be excreted. estimates GFR.
Urea: Partially reabsorbed, but mostly excreted.
Drugs/Medications: Excreted from the body.
See last slide
The blood pressure in the glomerulus is extraordinarily high (approximately 55 mm Hg compared to an average of 26 mm Hg or so in other capillary beds) and it remains high across the entire fenestrated capillary bed. This is because the glomerular capillaries are drained by a high-resistance efferent arteriole whose diameter is smaller than the afferent arteriole that feeds them. As a result, filtration occurs along the entire length of each glomerular capillary and reabsorption does not occur as it would in other capillary beds.
