Lecture 7: Renal Blood Flow Flashcards
What are the normal and dysfunction levels for BUN?
10:1 = Normal = Normal filtering GFR
>20:1 = Decreased GFR = Pre-Kidney failure
<10:1 = Full kidney failure
If you are not given the glucose or BUN concentrations how do you calculate Osmolality?
Osmolality = (2 x sodium)
Total renal blood flow is approximately what percentage of resting cardiac output?
20%
How many liters of filtrate are produced per day?
180 L
Substances leaving the plasma must pass through filtration barriers before entering the tubule lumen, what are they?
1) Glomerular capillary endothelium (pores)
2) Basal lamine (acellular basement membrane)
3) Filtration slits between the pedicles of the podocytes in the inner layer of Bowman’s capsule
What is found on the glomerular capillary wall epithelium; how does this affect permability compared to other capillaries?
- Many large pores between enodthelial cells
- Many large holes (fenestrations) in the endothelial cells
* 100x more permeable to H2O and solutes than other capillaries
What is the largest protein we want filtering throught the Bowman’s capsule and approximately what percent gets through?
- Albumin (smallest plasma protein)
- <1%
What 2 factors constitue the selectivity of the basment membrane to particle movement?
- Size of particle
- Charge of particle
What causes the negatively charged molecules to be repelled from filtration barrier; found in which layers?
Glycoproteins in basement membrane and podocytes
Basment membrane prevents molecules larger than what from passing through?
7 nm or no greater than 40,000 daltons
Discuss the filtraton differences of postive, neutral, and negatively charged molecule?
Positive: More filtered
Neutral: In the middle
Negative: Less filtered
*Notice the filtration rate as size changes for each
What is Hematuria and what is it indicative of?
- RBC’s in the urine
- Indicative of renal or kidney diseases/presence of kidney stones
How much protein is normally excreted in the urine daily, what is it called when more than this value is excreted?
- 150 mg
- Proteinuria = >150 mg excreted
What causes albuminuria?
Due to disruption of the negative charges (glycoproteins) within the basement membrane.
What are Tamm-Horsfall proteins; derived from?
Low-molecular weight proteins (LMWP) derived from the cells of Thick-ascending limb, accounts for 25 mg of daily protein excretion
Function of Podocytes?
- Structural support for basement membrane
- Repel negatively charged plasma proteins
Podocyte damage is commonly referred to as what syndrome; does this cause renal failure?
- Nephrosis
- Usually does not cause renal failure initially. Damage disrupts the relationship between podocytes and basement membrane = loss of strucutral support
The juxtaglomerular apparatus is made up of what 2 cells types?
1) Macula Densa (sensor cells)
2) Juxtaglomerular cells (aka granular cells) - renin
What do the Macula densa cells sense?
- Salt content
- Fluid volume
What 2 things do the Macula densa cells do if they sense LOW salt and LOW fluid volume?
1) Tell the granular cells (juxtaglomerular) to release renin
2) Dilate the afferent arterioles of the glomerulus = increased glomerular hydrostatic pressure
The juxtaglomerular cells secrete renin in response to what 3 things?
1) Beta-adrenergic stimulation
2) Decreased renal perfusion pressure
3) Signals from the Macula densa
What causes juxtaglomerular cells to release renin?
Decreased renal arterial pressure = Decreases stretch = decreased intracellular calcium concentration.
What are the 3 major mechanisms for the regulation of renin release?
1) Perfusion pressure (low = renin release)
2) Sympathetic nerve activity (activation = renin release)
3) NaCl delvivery to macula densa (low = renin release)
What is Tubuloglomerular feedback?
When NaCl is decreased (sensed by Macula densa), Renin secretion is stimulated and vice versa.
If the blood flow or blood pressure in the afferent arterioles decreases for any reason, what is stimulated?
Renin-angiotensin-aldosterone triad (RAAS)
What is the function of renin?
Converts angiotensinogen —> angiotensin I
Which hormone does angiotensin stimulate the secretion of; and its function?
- Aldosterone
- Increases the reabosrption of Na and H2O to increase blood volume, thus increasing BP
Angiotensin I is converted to what, by what enzyme; function of its converted form?
- Angiotensin II by ACE
- Causes system vasoconstriction in attemp to increase BP
How does a Beta-blocker affect renin levels?
Decreases Renin
What are the 3 things that ultimately determine GFR?
1) Renal blood flow
2) Resistance to flow
3) Permeability of glomerular basement membrane
What is the GFR value for normal, kidney disease, and kidney failure?
Normal: 60-120
Kidney disease: 15-60
Kidney failure: 0-15
What kind of molecules are free to pass from blood into the glomerular capsule?
Glucose, amino acids, water, and nitrogenous wastes
Keeping larger plasma proteins in the capillaries maintains which pressure; prevents what from occuring
Colloid osmotic pressure of the glomerular blood (πG); prevents the loss of all its water to the renal tubules
What is the net filtration pressure equation (think Starling)?
GFR = Kf (PG - PB - πG + πB)
What is the normal value of Bowman’s space (capsular) oncotic pressure (πB)?
Zero! Glomerular filtrate should contain little to no proteins
Vasoconstriction of the afferent arteriole does what to GFR and GHP?
Decrease GFR and GHP
Vasodilation of the afferent arteriole does what to GFR and GHP?
Increase GFR and GHP
Vasodilation of the efferent arteriole does what to GFR and GHP?
Decreases GFR and GHP
Vasoconstriction of the efferent arteriole does what to GFR and GHP?
Increases GFR and GHP
Decrease Kf and GFR are caused by what pathologies?
Renal disease, diabetes, HTN
Increased PB (Bowman’s capsule hydrostatic pressure) and decreased GFR caused by what pathologies?
Urinary tract obstruction (i.e kidney stones)
Increased πG and decreased GFR caused by what pathologies?
Decreased renal flow, increased plasma proteins
The GFR increases mainly as a result of decreased what (think autonomics)?
Sympathetic nerve activity
What 4 changes can lead to edema?
- Increased capillary hydrostatic pressure (heart failue)
- Decreased plasma oncotic pressure (hypoproteinemia)
- Increased capillary permeability (histamine/bradykinin)
- Lymphatic obstruction
What 2 drugs decrease GFR, how?
1) NSAIDs: afferent vasocontriction
2) ACE inhibitors: decrease efferent vasoconstriction
What 4 drugs increase GFR, how?
1) Prostaglandins: vasodilator (afferent>efferent)
2) Angiotensin II: vasoconstrictor (efferent > afferent)
3) Norepi: vasoconstrictor (efferent), increases BP
4) ANP: afferent vasodilator, efferent vasoconstrictor
What kind of receptors for sympathetic innervation are found on the: afferent arteriole, JG apparatus, and collecting duct; which NT acts on them all?
Afferent: Alpha-1 (vasoconstriction)
JG apparatus: Beta-1 (renin secretion)
Collecting Duct: Alpha-1 (sodium reabsorption)
*The NT is norepinephrine
When is autoregulation functioning to maintain constant GFR; what MAP?
- Under normal conditions
- MAP = 80-180 mmHg
What 2 mechanisms are in operation for autoregulation?
1) Myogenic control (stretch receptors)
2) Tubuloglomerular
What 2 things does autoregulation adjust in the kidneys to maintain normal GFR?
1) Renal blood flow
2) Glomerular surface area
Tubuloglomerular mechaism of autoregulation is operates as what kind of feedback?
Negative feedback mechanism
Increase in GFR from an increase BP does affects Na+ delivery to macula densa how, which increases what?
- Increase Na+ delivery
- Increased ATP released
How does ATP release from Macula densa affect afferent arterioles?
ATP will be metabolized to Adenosine in the juxtaglomerular interstitium. Then combines with receptos in the afferent arterioles and causes vasoconstriction
When is autoregulation overrode?
During periods of extreme stress or blood loss (hemorrage). Sympathetic stimulation will take precedent.
What 2 important results occur from the autoregulatory mechanism being overridden by the sympathetic nervous system?
1) Activity of kidney temporarily lessend/suspened in favor of shunting blood to other vital organs
2) Lower GFR reduces fluid loss, thus maintaining higher blood volume and BP for other vital functions.
*Renal function basically stops
During extreme stress what happens to the afferent and efferent arterioles?
- Intense vasoconstriction resulting in decreased GFR
