Renal I- Physiology Review

Question 1

General kidney info:

location

% of CO?

innervation of kidney?

Innervation of bladder and ureters?

Answer 1

• Located retroperitoneal at L2
• Receives 25% of CO
  
  • very low O2 extration ratio
• Innervation of kidney:
  
  • SNS via preganglionic fibers (T8-L1
  • Pain (SNS) T10-L1
  • PSNS CN X
• Innervation of bladder and ureters
  
  • motor: PSNS S2-S4
  • sensory: SNS T11-L2

Question 2

How does blood flow through the kidney?

Answer 2

• Renal artery ->Arcuate arteries-> interlobular arteries
• Afferent arterioles (leading to glomerular tuft)
• Glomerular capillaries and bowman’s capsule->
• efferent arteriole-> peritubular capillaries/vasa Recta ->
• venous system

Question 3

How do the arterioles affect GFR?

How do vasoconstricting medications affect the GFR?

Answer 3

• contraction of efferent arteriole = increased GFR
• contraction of afferent arteriole = decreased GFR
• Vasoconstricting medications:
  
  • mild/moderate causes preferential constriction of efferent, causing increase in GFR
  • very high causes afferent constriction (decreases GFR in shock situations)

Question 4

Cortex of the kidney:

What are the anatomical parts?

How much blood flow?

How is blood flow regulated through the cortex?

Answer 4

• Anatomical parts:
  
  • glomerulus
  • proximal tubule
  • distal tubule
  • portion of the collecting duct
• Receives 94% of the total blood flow (approx 5 ml/L/g
• Regulated by vasoactive compounds
  
  • adenosine induces vasoconstriction (opposite of usual effect) by stimulating the adenosine A1 receptor
  • stress-> SNS -> renal cortical constriction and potential tubular ischemia
  • **Kidney has no B2 receptors! Epi=vasoconstrict

Question 5

What is the PO2 in the cortex?

What is the extraction ratio of the cortex?

Answer 5

• 50 mmHg with an 18% extraction ratio

Question 6

Medulla of the Kidney:

What is the functional part of the kidney in the medulla?

How much blood flow does it receive?

How is the blood flow regulated?

Answer 6

• Contains the loop of Henle
• Receives 6% of total blood flow (approx 0.03mL/min/g)
• Regulated by:
  
  • Prostaglandins (PGs) and NO, promoting vasodilation
  • PGs and NO + adenosine A1 in cortex work to shunt blood into the medulla
  • NSAIDS disrupt this compensatory mechanism and can cause medullary ischemia by inhibiting PGs

Question 7

What is the PO2 in the madulla?

What is the extraction ratio?

Answer 7

• PO2 = 8 mmHg with an 80% extraction ratio
• Severe hypoxia can develop in the medulla despite relatively adequate RBF
• High extraction ratio b/c this area is highly metabolically actively

Question 8

What happens with medullary ischemia in hemodynamically-mediated renal injury?

Answer 8

• First response is to increase active NaCL absorption
  
  • this increases metabolic activity and O2 demand, decreasing O2 delivery
• compensation attempted via cortical vasoconstriction and flow redistribution
  
  • ultimately ATP becomes depleted and NaCl reqbsorption decreases
  • causes increased NaCl in tubular fluid
  • renin is released from macula densa and afferent arteriole is constricted

Question 9

What are the different types of nephrons?

Answer 9

• Cortical nephrons (recieve 85% of RBF and make up majority of the nephrons)
  
  • found in outer/middle cortex
  • short loop of henle
  • efferent arterioles drain into peritubular capillaries
• Justamedullary nephrons (recieve 10% of RBF)
  
  • found in inner renal cortex
  • longer loop of henle to reach inner medulla
  • efferent arterioles drain into specialized peritubular capillaries (vasa recta)
    
    • countercurrent mechanism

Question 10

What is the glomerulus?

What are the 5 components?

Answer 10

• Glomerulus: capillary network that originates from an afferent arteriole and are surrounded by dilated blind end of the nephron (bowman’s capsule)
• 5 components:
  
  • capillary endothelium- produces NO and endothelin-1 which vasodilate and constrict
  • glomerular basement membrane, and visceral epithelium- make up the filtration barrier
  • parietal epithelium (bowman’s capsule)
  • mesangium (interstitial cells)- contract in response to angiotensin II and other vasoconstrictors to decreasesflow and GFR

Question 11

What happens in the proximal convoluted tubule?

(5 actions)

Answer 11

• Reabsorption
  
  • PCT is a direct continuation of bowman’s capsule
    
    • the higher the peritubular pressure, the less reabsorption occurs
• Actions:
  
  • 65% of H20, Na, K, Cl reabsorpion (ATP req for Na)
  • almst 100% reabsorption of glucose, lactate, AA
    
    • glucose max is 375 mg/dL
  • H+ exchanged for bicarb
  • Ca reabsorbed under influence of PTH
  • waste products actively excreted ( bile salts, urea, Cr, dopamine, drugs)

Question 12

What happens in the loops of Henle?

Answer 12

• Ultrafiltration- interstitial osm increases from 300 to 1500
• Continuation of PCT
• Descending loop of Henle:
  
  • permeable to H20, thus it passively leaves the tubule
• Ascending loop of henle
  
  • impermeable to H2O, but d/t highly concentrated ultrafiltrate, NaCl passively diffuses out into the interstitial
• Thick ascending loop of henle
  
  • thickness caused by active transport channels in the epithelium layer
  • high metabolic activity, susceptible to ischemia
  • Na/K/2Cl cotransporter to increase osm of interstitial and dilute urine

Question 13

What is the vasa recta?

Answer 13

• network of capillaries surrounding the loop of henle that take up and/or release Na, Cl, and H2o passively along the gradient

Question 14

What is the Juxtaglomerular apparatus?

What is the function?

How is this achieved?

Answer 14

• made of of the distal convoluted tubule and the afferent arteriole.
• main function is to control BP and filtration rate
  
  • mesangial (sm muscle) cells contract, decreasing surface area of glomerulus and decreasing GFR (in response to vasoconstrictors)
  • granular cells secrete renin in response to:
    
    • Beta 1 stimulation
    • decreased RBF which leads to decreased GFR

Question 15

What happens in the distal convoluted tubule?

Answer 15

• electrolyte, H2O, and pH fine tuning
• High metabolic activity
• 10% of Na/H2O reabsorption, also Cl reabsorption d/t
  
  • ADH mediated V2 receptors
  • aldosterone

Question 16

What is aldosterone?

When is it released?

What does it do?

Answer 16

• Aldosterone is a steroid released by the zona glomerulosa of the adrenal cortex
• Released in response to:
  
  • angiotensisn II
  • ACTH
  • SNS stimulation
  • low Na
  • high K
• Aldosterone increases active Na reabsorption via K exchange (this takes a few hours to work)
  
  • excessive aldosterone causes hypokalemic acidosis

Question 17

Where is ADH released from?

When is it released?

What is the E1/2t of ADH/AVP?

Antidiuretic hormone (ADH)= Vasopressin (AVP)

Answer 17

• ADH is released from the posterior pituitary gland in response to:
  
  • chemoreceptors (increased ECF Na levels or osm >280
  • baroreceptors (atrial, aortic, carotid)
    
    • hypotension is most potent trigger for ADH release
  • Angiotensin II
  • stress via cortical input
  • surgical stimulation (for 2-3 days afterward) and hypotension d/t anesthesia (not directly the anesthetics)
• E1/2t ADH/AVP = 5-15 min

Question 18

What does the release of ADH result in?

Answer 18

• V2 receptor stimulation
  
  • increased cAMP->PK activation, causing migration and fusion of pre-formed vesicles containing aquaporin-2 water channels
  • thus increasing H2O permeability
• with high amts of ADH can cause V1 receptor stimulation
  
  • causes renal cortical vasoconstriction (primarily efferent arteriole)
• Stimulates thirst

Question 19

What happens in the collecting ducts?

Answer 19

• Electrolyte, H2O, and pH fine tuning
• 10% of Na and H2O reabsorption
  
  • under influence of ADH
  • principle cells reabsorb Na (and water) in exchange for K
  • capable of secreting H+
    
    • intercalated cells secrete H+ and reabsorb bicarb

Question 20

Summary of the four major kidney functions

Answer 20

• Control of fluid and inorganic ion balance
• removal of metabolic wastes and chemicals from the circulation (via filtration or secretion)
• gluconeogenesis
• endocrine function/hormone secretion
  
  • fluid balance (renin, PGs, kinins)
  • RBC production (EPO in response to decreased renal PO2)
  • bone health (1,25-dihydroxyvitamin D3)

Question 21

Summary of urine production when hypovolemic

With hypervolemia?

Answer 21

• Hypovolemia:
  
  • SNS and angiotensin II = vasoconstriction = decreased GFR and increased Na reabsorption
  • aldosterone = increased Na reabsorption
  • vasopressin (ADH) = increased H2o reabsorption in collecting ducts
• Hypervolemia
  
  • ANP= vasodilation = increased GFR
  • decreases SNS and angiotensis II = vasodilation = increased filtered Na
  • increased capillary hydrostatic pressure = decreased reabsorption of Na
  • decreased aldosterone = decreased Na reabsorption in DCT and CD
  • decreased ADH = decreased H2O reabsorbed in CD

Question 22

What are the mechanisms of autoregulation?

(9)

Answer 22

• myogenic (local feedback)
  
  • arteriole stretch or lack of stretch causes reflex vasoactivity of the afferent arteriole
• first response to renal ischemia = increase Na/Cl reabsorption in TALOH
• SNS (esp Alpha 1) and angtiotensin II
  
  • first efferent vasoconstriction
  • effects seen on afferent arteriole when levels are really high
• AVP/ADH causes reabsorption of H2O + efferent vasoconstriction
• Adenosine: decreases renin w/high NaCl + redistributes RBF
  
  • afferent vasoconstriction + selective vasodilation of deep cortical vasculature
• tubuloglomerular feedback
  
  • high Cl sensed in macula densa of JA indicates high GFR, causing release of adenosine, decreased renin release, and NO synthatase inhibition
• PGs: produced via ang II activation d/t renal ischemia, hypotension, or physiologic stress and cause renal vasodilation
• Natriuretic peptides in response to stretch
  
  • block reabsorption of Na in DT and CD and increases GFR, decreases renin/aldosterone release
• NO: opposes vasoconstrictive effects of SNS/angiotensin, promotes Na/H2O excretion, influences tubuloglomerular feedback

Question 23

What is normal RBF?

What is autoregulation maintained between?

What impairs autoregulation?

Answer 23

• RBF is 1200 ml/min (25% of CO)
  
  • 2/3 is to the cortex
• Autoregulated btwn MAP 80-180
• Autoregulation maintained with most anesthetics
• Autoregulation impaired by:
  
  • CCB
  • sepsis
  • ARF
  • CPB
  • NO

Question 24

What is normal GFR?

What directly impacts GFR?

Why does GFR matter?

Answer 24

• GFR is approx 90-140 ml/min (180 L/day)
• Autoregulation of GFR directly impacted by RBF
  
  • b/c blasma hydrostatic pressure is the easiest and most realistic variable to manipulate
• Why does it matter?
  
  • too slow = tubular fluid would pass through too slowly, causing complete reabsorption and no UOP
  • too fast = passes too fast and unable to reabsorb the substances that need to be conserved

Question 25

What makes GFR?

What can affect each component?

Answer 25

• GFR = permeability of filtration barrier = difference b/t hydrostatic pressures - oncotic pressure of plasma
• Glomerular hydrostatic pressure affected by:
  
  • efferent/afferent arteriole tone
  • hyper/hypovolemia
  • MAP outside the auto regulation range
• Filtrate hydrostatic pressure affected by:
  
  • Bowman’s capsule pressure
• Plasma oncotic pressure affected by:
  
  • alterations in protein
  • anemia
• permeability of filtration barrier affected by:
  
  • integrity of the endothelial glycocalyx

Question 26

What are some methods of renal protection?

Answer 26

• Low dose dopamine- does NOT decrease incidence of ARF, dialysis, or mortality despite having diuretic activity
• Fenoldopam- DA-1 specific agonist
  
  • may help preserve post-op renal function in high risk patients
• Research ongoing for:
  
  • PGE-1
  • Natriuretic peptide
• Renal protection in shock:
  
  • vasopressors
  • NE (if MAP increased to >60 it will improve RBF more than the vasoconstriction will decrease it
  • vasopressin (increased renal perfustion pressure and preferentially the efferent arteriole)