Exam 3 - Lecture 36 (Glomerular Filtration and its Regulation) Flashcards
What % of blood leaves the glomerulus as filtrate?
15-20%
The filtration barrier separates on basis of _____ and _____.
size and charge
What is the size and charge of the fenestrated epithelium?
Size = Large pores (60-80 nm) Charge = polyanionic glycoprotein glycocalyx (neg. charge)
What is the size and charge of the lamina rara interna and externa?
Size = does not filter based on size Charge = Polyanionic non-collagenous proteins (neg. charge)
What is the size and charge of the lamina rara densa?
Size = Collagenous proteins Charge = Does not filter based on charge
What is the size and charge of the slit diaphragm?
Size = Perforated with small pores Charge = Podocytes are covered with polyanionic glycoprotein glycocalyx (neg. charged)
What size and charge does the glomerulus prefer for filtration?
Positively charged and small
Between anionic and cationic molecules, which is harder for the glomerulus to filter?
anionic (esp. when large)
When would a cationic molecule be hard for the glomerulus to filter?
If it is large in size
How are neutral molecules filtered by the glomerulus?
Only based on size
Filtration is designed to exclude _____.
most proteins
Which molecule will most easily cross the filtration barrier?
A) Na+ (small and pos. charged)
B) Cl- (small and neg. charged)
C) Gamma globulin (large [150 kDa] and neg. charged)
D) Dextran-70 (large [70 kDa] and neutral)
A) Na+ (small and pos. charged)
Where do Starling’s Forces operate?
At any capillary bed
What are the two types of hydrostatic pressure?
- Capillary HS pressure (Pc)
2. Bowman’s space HS pressure (Pbs)
What are the two types of oncotic pressure?
- Capillary oncotic pressure (πc)
2. Bowman’s space oncotic pressure (πbs)
What is capillary hydrostatic pressure?
Pressure of the glomerulus pushing out
What is Bowman’s space hydrostatic pressure?
Pressure of Bowman’s space pushing back on the glomerulus
What is capillary oncotic pressure?
Pressure into the glomerulus by capillaries
What is Bowman’s space oncotic pressure?
Pressure out of Bowman’s space by small amount of proteins getting through; is usually NEGLIGIBLE
What is oncotic pressure?
Osmotic pressure generated by plasma proteins
How do you calculate the magnitude of the force favoring glomerular filatration and what is the meaning of the result?
Pc - (Pbs + πc); net pressure moving OUT
What is Kf?
Filtration constant
Which Starling’s force is negligible and almost always 0?
πbs
Changes in resistance to blood flow in afferent/efferent arterioles changes _____ and therefore _____.
Pc; GFR
Increased resistance in efferent arteriole _____ Pc and GFR.
increases
What happens if the efferent arteriole narrows?
Easier for blood to enter thru afferent arteriole and GFR increases.
Constriction of the afferent arteriole combined with dilation of the efferent arteriole will produce which effect?
A) Increased Pc, Increased GFR
B) Increased Pc, decreased GFR
C) Decreased Pc, increased GFR
D) Decreased Pc, decreased GFR
D) Decreased Pc, decreased GFR
Why do disease states alter GFR?
Because they change Starling’s Forces
What happens when you feed a dog grapes or raisins?
necrosis of the tubules –> renal failure
Kf = _____ x _____
permeability of capillary X filtration SA
Most disease states _____ Kf and SA for filtration
Decrease
What is an example of a human disease state that alters GFR?
Glomerular disease caused by Schistosoma mansoni (human blood fluke); leads to renal failure
What are 2 examples of veterinary disease states that alter GFR and what does each lead to?
- Lyme disease (Borreliosis) –> chronic renal disease
2. Ethylene glycol toxicity –> acute renal failure
What is an example of disease state that changes Kf?
Glomerular disease
What is an example of a disease state that changes Pc?
Acute renal failure
In acute renal failure, Pc can _____ due to impaired renal perfusion; this causes _____ in GFR.
decrease; decrease
What is an example of a disease state that changes πc?
Plasma protein levels increase and decrease
If πc increases, GFR _____.
decreases
If πc decreases, GFR _____.
increases
What is an example of a disease state that changes Pbs?
Obstructions such as uroliths or plugs that increase Pbs.
If Pbs increases, GFR _____.
decreases
If Pbs decreases, GFR _____.
increases
GFR is the sum of _____.
filtration rates over all functioning glomeruli (SNGFR X total # of nephrons)
GFR is the _____ of renal function.
main descriptor
What is acute renal failure/
Rapid (hrs/wks) but partially reversible decline in GFR.
What is clearance?
How efficiently the kidney can get rid of a substance.
When does clearance = GFR?
If substance is freely filtered by glomerulus and isn’t secreted or absorbed in the tubules
The tone of the afferent and efferent arterioles is important in regulating GFR. Which of the following statements is true?
A) Dilated afferent arteriole and normal efferent arteriole increases GFR
B) Normal afferent arteriole and constricted efferent arteriole decreases GFR
C) Constricted afferent arteriole and normal efferent arteriole increases GFR
D) Normal afferent arteriole and dilated efferent arteriole increases GFR
A) Dilated afferent arteriole and normal efferent arteriole increases GFR
What are the two types of markers used to measure clearance?
- Exogenous
2. Endogenous
What is the exogenous marker used for measuring clearance?
Inulin
What are the endogenous markers used for measuring clearance?
- Creatinine
2. BUN
What is an exogenous marker?
Something that is introduced
What is an endogenous marker?
Things we know are present in the ECF
What is the most commonly used endogenous marker?
Creatinine
How is creatinine filtered by the glomerulus?
Freely
Presence of creatinine in the blood is _____ proportional to GFR.
indirectly
What are the normal serum creatinine levels in dogs?
0.3 - 1.3 mg/dL
What are the normal serum creatinine levels in cats?
0.8 - 1.8 mg/dL
Why is BUN not as reliable as creatinine as a guide to renal function?
Up to 40% may be reabsorbed by the tubules
What do increases in BUN/creatinine mean?
At least 75% of nephrons are not functioning, but up to this point the kidney can still function
Which of Starling’s forces is the most important?
Pc (capillary hydrostatic pressure)
What is general autoregulation?
Intrinsic ability of an organ to maintain blood flow at a nearly constant rate despite changes in arterial perfusion pressure (systemic BP change)
What is renal autoregulation?
Point/range where changes in systemic BP do not affect the renal blood flow or the GFR (between 80 and 180 mm Hg).
What are the two goals of renal autoregulation?
- Prevent damage to glomeruli caused by spiking BP
2. Prevent fluctuations in BP from changing delivery of filtrate to tubules
What are the 2 mechanisms that the kidney uses for autoregulation?
- Myogenic mechanism
2. Tubuloglomerular feedback
What is the goal of the myogenic mechanism?
Prevent damage to glomeruli
What triggers the myogenic mechanism?
Fluctuations in BP changing transmural pressure in the AFFERENT arteriole
In the myogenic mechanism, increased BP elicits _____ and _____ blood flow.
vasoconstriction; decreased
In the myogenic mechanism, decreased BP elicits _____ and _____ blood flow.
vasodilation; increased
What is the speed of the myogenic mechanism?
Rapid changes (1-2 sec) in response to rapid BP changes
Which statement about the myogenic mechanism is true?
A) It is a slow acting response
B) The main effect is to constrict the efferent arteriole
C) It helps to protect the glomerulus
D) It is triggered in the efferent arteriole wall
E) It will reduce GFR in response to low BP
C) It helps to protect the glomerulus
What is the goal of tubuloglomerular feedback?
“Fine-tuning”; we don’t want too much or too little solute getting dumped into the nephron when the GFR changes
What is the trigger for tubuloglomerular feedback?
Fluctuations in BP change GFR meaning DT fluid composition is altered
What are the 3 steps to tubuloglomerular feedback?
- Low/High GFR produces low/high ultrafiltrate
- Low/High [ion] sensed by macula densa
- JGA changes arteriole resistance to autoregulate GFR
What is the speed of tubuloglomerular feedback?
Slower changes (10-12 sec) in response to slower BP changes
What cells are the macula densa cells directly connected to?
Juxtaglomerular cells of the afferent arteriole
What is the role of the extraglomerular mesangial cells?
Promote info transfer between MD and JG
What type of muscle are JG cells?
smooth
What do JG cells contain/produce?
renin
What are the 3 steps of the Renin-Angiotensin system?
- Liver releases Angiotensinogen
- JG cells produce Renin which catalyzes angiotensinogen –> Angiotensin I
- Angiotensin I is converted to Angiotensin II by Angiotensin Converting Enzyme (ACE)
Where does angiotensin converting enzyme come from?
lung
What 4 things does angiotensin II do?
- Systemic arteriolar vasoconstriction to increase BP
- Increases aldosterone secretion (adrenal cortex)
- Promotes ADH secretion (pituitary) and thirst
- Increases tubular NaCl uptake
What do you WANT to do to GFR when BP is high?
reduce it
How does tubuloglomerular feedback work to reduce GFR when BP is high (6 steps)?
- High Na+, K+, and Cl- sensed by NKCC2 on apical surface of MD
- MD releases ATP and/or adenosine
- ATP/adenosine activate receptors on EG mesangial cells
- Increased IC Ca2+ in EG mesangial cells causes same response in afferent arteriole smooth muscle and JG cells
- Afferent art. smooth muscle contracts (REDUCES GFR)
- JG cells are inhibited from releasing renin (REDUCES GFR)
What is released by the MD during tubuloglomerular feedback?
Adenosine/ATP when BP is high to lower GFR
PGE2 when BP is low to increase GFR
What does NKCC2 transport?
1 Na+
1 K+
2 Cl-
What effect does caffeine have on adenosine Rs?
Blocks Rs –> acts as diuretic
How does tubuloglomerular feedback work to increase GFR when BP is low (5 steps)?
- Low Na+, K+, and Cl- sensed by NKCC2 on apical surface of MD
- MD releases PGE2
- PGE2 causes afferent art. vasodilation (INCREASES GFR)
- PGE2 stimulates JG to release renin, increasing angiotensin II
- Angiotensin II causes 4 things to happen in the bloodstream that increase GFR
What 4 things does angiotensin II do in the bloodstream during tubuloglomerular feedback?
- Causes systemic vasoconstriction (INCREASES GFR)
- Preferentially contracts efferent over afferent arteriole (INCREASES GFR)
- Increases PGE2 production from MD
- Negatively feedbacks onto contralateral kidney to stop renin release
Tubuloglomerular feedback regulates GFR. When a high GFR is lowered by TGF, which of the following statements is accurate?
A) The trigger is low Na+, K+, and Cl- sensed by the macula densa
B) A key intermediate step is decreased IC Ca2+ in EG mesangial cells
C) Afferent arteriole smooth muscle contracts
D) JG cells release renin
E) Macula densa releases PGE2
C) Afferent arteriole smooth muscle contracts
How can chronic use of NSAIDs affect the kidney?
Can lead to acute renal failure
How do NSAIDs (esp. prolonged use) affect the autoregulation pathway?
They inhibit PGE2 production, so GFR cannot be raised when BP drops; leads to ischemic injury, acute renal failure, vomiting, and anorexia.
What is the sensor in the myogenic mechanism?
BP changes in afferent arteriole
What is the effector in the myogenic mechanism?
Afferent arteriole
What is the role of the myogenic mechanism?
Protection against injury
What is the response time of the myogenic mechanism?
Fast - adapts to changes up to 6 Hz
What is the importance of the myogenic mechanism?
No mechanism = no autoregulation
What is the sensor in TGF?
Ionic changes in the DT
What is the effector in TGF?
Afferent AND efferent arterioles
What is the role of TGF?
Regulation of GFR
What is the response time of TGF?
Slower - adapts to changes less than 0.1 Hz
What is the importance of TGF?
Less important than the myogenic mechanism; works with other mechanisms to control GFR and fluid homeostasis
Captopril is an angiotensin converting enzyme (ACE) inhibitor. Bases on what you know about the renin-angiotensin system, which of the following statements is correct?
A) Captopril reduces Angiotensin II and increases GFR
B) Captopril reduces Angiotensin II and decreases GFR
C) Captopril increases Angiotensin II and increases GFR
D) Captopril increases Angiotensin II and decreases GFR
B) Captopril reduces Angiotensin II and decreases GFR
