Chapter 2: Renal Physiology Flashcards
What are the 3 components of the glomerular capillary wall or filtration barrier?
- Capillary endothelium (innermost layer) - closest to blood side
- Basement membrane (medium layer)
- Visceral epithelium (outermost layer) - closest to urinary side
What are 3 components of the juxtaglomerular apparatus?
- Macula densa (sense Na)
- Juxtaglomerular cells (sense pressure in afferent arteriole, release renin)
- Mesangial cell (release prostaglandin which contributes to renal vasodilation)
List the permeability of anionic, neutral or cationic macromolecules across the glomerular capillary wall in order of most to least permeable.
Most permeable = cationic
In the middle is neutral
Least permeable = anionic
What is the definition of renal clearance of a substance?
The volume of plasma that contains the amount of substance excreted in urine in 1 minute.
What is the standard clearance formula? (Also, GFR)
GFR = UxV/Px
Ux = concentration of substance in urine V = flow rate Px = concentration of substance in plasma
Which side of the capillary endothelium of the glomerulus is negatively charged?
Luminal side
The basement membrane of the filtration barrier is divided into which three layers?
Lamina rara interna (endothelial side)
Central lamina densa
Lamina rara externa (epithelial side)
Where are podocytes located?
Visceral epithelial cells of the filtration barrier (outermost layer) - closest to the urinary side of the barrier
The glomerular capillary wall has both size and charge selectivity. Where do each mainly occur?
Size selectivity occurs mainly in the lamina densa of the glomerular basement membrane (smack dab in the middle).
Charge selectivity occurs in the negatively charged sialoglycoproteins and peptidoglycans of the capillary endothelium, lamina rara interna, lamina rara externa and visceral epithelium (basically everywhere else).
What is the average hydrostatic presure along the glomerular capillary?
55 mm Hg
Why is the ultrafiltration constant (Kf) in the glomerulus so much higher than that of systemic capillaries?
The morphology of the glomerulus has a much higher surface area and the unit permeability if >100 times that of skeletal muscle capillaries. Furthermore, the Kf is not constant and can change in disease states or in response to hormones.
What happens to RBF and GFR with decreased afferent resistance?
Increased RBF and Increased GFR
What happens to RBF and GFR with decreased efferent resistance?
Increased RBF and decreased GFR
What happens to RBF and GFR with increased efferent resistance?
Decreased RBF and Increased GFR
What happens to RBF and GFR with increased afferent resistance?
Decreased RBF and Decreased GFR
Norepinephrine causes afferent and efferent vasoconstriction, but which predominates?
Efferent; therefore there is minimal changes in GFR with decrease in RBF
List substances that cause vasodilation of the afferent arteriole.
Acetycholine Nitric oxide Dopamine Bradykinin Prostacyclin Prostaglandin E2 (does not effect efferent) Prostaglandin I2
List substances that cause vasoconstriction of afferent arteriole.
Norepinephrine
Angiotensin II
Endothelin
Thromboxane
Which substance causes vasoconstriction of efferent arteriole but not the afferent?
Vasopressin
What is normal GFR for the dog? For the cat?
Dog: 3-5 ml/min/kg
Cat: 2.5-3.5 ml/min/kg
How many percentages of the cardiac output goes to kidneys?
25%
Within what perfusion pressure range that the kidneys are able to maintain the GFR and RBF (at relatively constant rate) without much variation?
80 – 180 mmHg
What are the two mechanisms that explains the autoregulation of kidneys blood flow?
- Myogenic mechanism
- Smooth muscle tends to contract when stretched and relax when shortened
- Fast: 1 – 2 sec delay - Tubuloglomerular feedback
- Happens on an individual nephrons
- When the extraglomerular mesangial cells at the juxtaglomerular apparatus sense increased NaCl flowing through the distal tubules, it will transport the NaCl through the cells and generate adenosine. Adenosines and angiotensin II will then together cause vasoconstriction of the afferent arteriole of that glomerulus.
- Slower: 10-12 sec delay
What is the filtration fraction (FF) in dogs and cats?
The filtration fraction is the fraction of plasma flowing through the kidneys that is filtered into the Bowman space.
FF = GFR/RPF
In the dog and cat, values for FF are 0.32 to 0.36 and 0.33 to 0.41, respectively.
What are the two routes that the solutes and water move across the renal tubule epithelium? Which one is the main one for water and solute resorption?
- Paracellular (between cells)
- Transcellular (through cells)
The paracellular route accounts for only 1% of the surface area available for reabsorption and 5% to 10% of water transport, whereas the transcellular route accounts for 99% of the available surface area and 90% to 95% of water transport.
In a nephron, which segment is the major site of bicarb resportion?
Proximal renal tubules
What are the four types of transport processes that contribute to renal tubular reabsorption?
Passive diffusion
Facilitated diffusion
Primary active transport
Secondary active transport
Among the four types of transport processes, which is the major types of glucose and amino acid transport?
facilitated diffusion
How does the filtered protein being transport through the membrane?
Pinocytosis
What are the two main steps in the urinary concentrating mechanism?
- Transport of sodium chloride without water from the ascending limb of LOH
- Vasopressin (ADH) increases water permeability of collecting duct
What is the primary energy-requiring step of the urinary concentrating mechanism?
Active transport of sodium chloride from thick portion of ascending limb of LOH
Which part of LOH is impermeable to water?
Ascending limb
Where does the active transport of Na+, K+ -ATPase occur specifically in the tubular cells?
Basolateral membrane
How does furosemide function?
Impairs distal sodium reabsorption by competing with chloride for luminal carrier of NKCC2 (Na+, K+, 2Cl- carrier).
Why chloride with furosemide?
It’s the rate limiting step in the transport process
What are the three segments of the collecting duct?
Cortical collecting duct, outer medullary collecting duct, inner medullary collecting duct
How does the inner medullary collecting duct maximally concentrates urine?
Add urea to the interstitium, whose permeability is increased by ADH
The outer medullary collecting duct is impermeable to what ion?
Sodium
Describe the role of the vasa recta
Provides water to the hypertonic interstitium and gives solutes to hypotonic interstitium. Aids in the countercurrent exchange.
Where in the nephron and how is glucose reabsorbed?
In the proximal tubule, through sodium-glucose symporters (SGLT-1 and SGLT-2).
How does glucose leave the tubular cell across the basolateral membrane?
Through facilitated diffusion via the GLUT uniporter.
Which sodium-glucose symporter has high capacity and low affinity for glucose?
SGLT-2.
Which sodium-glucose symporter has low capacity and high affinity for glucose?
SGLT-1.
Define Tmax
Tubular transport maximum: maximal amount of a substance that can be transported by the tubules.
Range from higher to lower Tmax the following solutes: glucose, phosphate, amino acids.
Amino acids > glucose > phosphate.
What helps mantain the sodium gradient in the tubular cell?
The Na+,K+-ATPase pump in the basolateral membrane, which continuously removes Na+ out of the tubular cell.
What is the role of PTH on phosphate’s Tmax?
PTH decreases the Tmax for phosphate so it increases renal phosphate excretion.
What phosphate transporters do you know and where in the nephron are they?
NaPi-IIa and NaPi-IIc. In the proximal tubule.
What happens to urea reabsorption in the proximal tubule during higher tubular flow rates?
Less urea is reabsorbed at higher tubular flow rates.
Increased tubular flow –> decreased reabsorption of water –> decreased tubular fluid urea concentration –> decreased concentration gradient of urea across tubular epithelium.
Which solute uses pinocytosis for its reabsorption?
Low-molecular weight proteins.
What urea transporters are present in the kidney and where are they located?
- UT-A1 and UT-A3 (vasopressin-responsive): inner medullary collecting duct.
- UT-A2: descending limb of Henle’s loop.
- UT-B: descending (arterial) vasa recta. (also expressed in blood-brain-barrier, intestine and erythrocytes).
List all sodium reabsorption mechanisms (including location in the nephron).
- Proximal tubule: Na+-H+ antiporter, and glucose, amino acids or phosphate cotransporters.
- Ascending limb of Henle’s loop: Na+-K+-2Cl- pump (competitively inhibited by furosemide) and paracellular transport (lumen positive potential).
- Distal convoluted tubule: Na+-Cl- cotransporter (inhibited by thiazide diuretics) and apical sodium channels (ENaCs).
- Cortical collecting duct: apical sodium channels (ENaC).
