Renal Blood Flow
List causes of edema?
•Increased capillary hydrostatic pressure (as occurs when venous pressures become elevated by gravitational forces, volume expanded states, in heart failure or with venous obstruction) •Decreased plasma oncotic pressure (as occurs with hypoproteinemia) •Increased capillary permeability caused by proinflammatory mediators (e.g., histamine, bradykinin) or by damage to the structural integrity of capillaries so that they become more "leaky" (as occurs in tissue trauma, burns, and severe inflammation) •Lymphatic obstruction (as occurs in filariasis)
Explain why a patient would have excessive albumin in the urine?
Albuminuria can result due to disruption of the negative charges within the basement membrane.
Generally, GFR is influenced by three things. List them?
Autoregulation or Intrinsic (myogenic mechanism & tubuloglomerular feedback mechanism) - from 80 mm Hg to 180 mm Hg renal blood flow doesn't change due to this. Hormonal Regulation Sympathetic Control (extrinsic)
In diabetic nephropathy, which barriers of the filtration barrier break down?
Glomerular capillary endothelium, Basement Membrane. Barrier 3 is left (podocytes)
What is Effective Renal Blood Flow (ERBF in ml/min) and how is it calculated?
Only about 90% of the RBF actually reaches the nephrons at the glomerulus, therefore; this number indicates the estimated, or effective, blood flow that actually reaches the nephrons. ERBF = 0.9(RBF)
How does activation of the sympathetic nerve fibers in the afferent arterioles affect renin secretion?
increases renin secretion
________ is the clinical term used when red blood cells are present in the urine.
Hematuria Presence of blood is indicative of damage to the kidney, such as in renal or kidney disease. Sometimes, blood may be present because of the presence of kidney stones.
How is increased sympathetic activity going to affect GFR?
It will decrease GFR by increasing afferent arteriole resistance.
Which cells surround the afferent arteriole of the kidney?
Juxtaglomerular cells (granular cells) They act as high-pressure baroreceptors
How does low/High perfusion in the afferent arterioles affect renin secretion?
Low perfusion = stimulates renin secretion High perfusion = inhibits renin secretion
List/describe the two types of cells that make up the Juxtaglomerular Apparatus?
Macula densa = Sense the salt content and the volume of fluid within the tubule. If either is LOW, it 1) tell the granular cells to release renin, and 2) dilate the afferent arteriole of the glomerulus (by secreting a little ADH). Juxtaglomerular cells (granular cells) = secrete renin in response to three things: 1) beta-adrenergic stimulation, 2) decreased renal perfusion pressure and 3) signals from the macula densa.
Give the Equation for Net Filtration Pressure
NFP = Glomerular blood hydrostatic pressure (PG) - Bowman's (capsular) hydrostatic pressure (PB) - Glomerular blood colloid osmotic (oncotic) pressure(πG) PG-glomerular capillary hydrostatic pressure (GCP) = simply blood pressure (OUTWARD) PB-Bowman's space(Capsular) hydrostatic pressure (CHP) = (INWARD) πG-Glomerular capillary oncotic pressure = (INWARD)
List Drugs that decrease GFR?
NSAIDs: afferent vasoconstriction ACE Inhibitors: decrease efferent vasoconstriction
What can damage to Podocytes lead to?
Nephrosis The damage to the podocyte disrupts the delicate relationship between the podocyte and the basement membrane, resulting in loss of the structural support usually supplied by the podocyte. Usually do not cause renal failure initially.
Compare Nephrosis and Nephritis?
Nephrosis = Podocyte damage Nephritis = syndrome of renal inflammation
Compare O2 Consumption in the brain and kidney?
O2 consumption is high and only the brain has a higher O2 consumption.
Failure to remove waste products of metabolism by the kidneys will allow them to quickly accumulate to toxic levels initiating a condition known as ________.
uremia
With regards to the following value ranges of the GFR, what do they correspond to? 0-15 15-60 60-120
0-15 = kidney failure 15-60 = kidney disease 60-120 = normal
Substances leaving the plasma must pass through three filtration barriers before entering the tubule lumen. List them?
1. Pores between and the fenestrations within the glomerular capillary endothelium 2. Acellular basement membrane with collagen for structural strength and negatively charged glycoproteins that discourage the filtration of small plasma proteins (albumin). 3. filtration slits between the foot processes of the podocytes in the inner layer of Bowman's capsule
Give the equation for Osmolarity?
2 (serum Na+) + serum glucose/18 + BUN/2.8 Note: if no glucose or BUN are given then just use 2 x serum Na+.
Total renal blood flow is approximately _____% of resting cardiac output.
20%
What is BUN and what are normal BUN/Creatinine ratio? <10:1 10:1 >20:1
Blood Urea Nitrogen <10:1=Full Kidney Failure 10:1 =Normal=Normal filtering and GFR >20:1 =Decreased GFR=Pre-Kidney Failure
Explain how decrease/increase in renal arterial pressure affects the action of the juxtaglomerular cells?
Decrease in renal arterial pressure results in decreased stretch, decreased intracellular calcium concentration, increase cAMP, and increased renin release from the juxtaglomerular cells. Increase in renal arterial pressure inhibits renin release.
When can Autoregulation be overridden?
During periods of extreme stress or blood loss, sympathetic stimulation overrides the autoregulatory mechanisms of the kidney. Increased sympathetic discharge causes intense constriction of all renal blood vessels. Two important results occur: 1) The activity of the kidney is temporarily lessened or suspended in favor of shunting the blood to other vital organs 2) The lower GFR reduces fluid loss, thus maintaining a higher blood volume and blood pressure for other vital functions. As you can see, renal function has almost stopped.
GFR is dependent on which factors? A. Pressure gradient across the filtration barrier (NFP) B. Blood circulation throughout the kidneys C. Permeability of the filtration barrier (through 3 layers) D. Filtration surface area E. All of the Above
E. All of the Above
Where are macula densa cells found?
In the distal convoluted tubule.
Explain the Myogenic mechanism for controlling GFR? Compare myogenic response to increased BP to Decreased BP.
Increased Blood Pressure leads to afferent arteriole vasoconstriction and efferent arteriole vasodilation. This leads to a decrease in glomerular hydrostatic pressure and therefore decrease in GFR. Decreased Blood Pressure leads to afferent arteriole vasodilation and efferent arteriole vasoconstriction. This leads to a increase in glomerular hydrostatic pressure and therefore Increase in GFR.
______ contain negatively charged glycoproteins, which repel negatively charged plasma proteins and prevent them from exiting the blood.
Podocytes
With regards to charge, which substances are most readily filtered? And what is the relationship between molecular size and filtration?
Positively charged substances are more easily filtered. As Molecular size increases, filterability decreases.
List Drugs that increase GFR?
Prostaglandin: vasodilator (afferent > efferent) Angiotensin II: vasoconstrictor (efferent > afferent) Norepinephrine: vasoconstrictor, increases blood pressure ANP: afferent vasodilator, efferent vasoconstrictor
________ is excretion of proteins in urine is more than 150 mg/day.
Proteinuria Only 15 mg is albumin and the rest are low molecular weight proteins (LMWP)
Give the equation for the clearance of PAH (para-aminohippurate)?
RPF= CPAH =(UPAH)xV/PPAH RPF = Renal Plasma Flow CPAH = Clearance of PAH UPAH = Urine Concentration V = Urine Volume PPAH = Arterial Concentration *remember that RBF = RPF/1-HCT
Afferent arterioles respond to changes in pressure by either constricting or dilating. During vasoconstriction of the afferent arteriole, blood flow is significantly decreased going into the glomerulus. How does this affect Net filtration pressure, Glomerular blood hydrostatic pressure (Glomerular capillary blood pressure), and GFR?
Results in NFP, Glomerular Blood Hydrostatic Pressure (PG) and decrease in GFR
What is the purpose of the Juxtaglomerular Apparatus?
The JGA has the ability to sense and respond to changes in both arterial and tubular flows and coordinate the processes of reabsorption and glomerular filtration.
What is the maximum size of substance that will pass through the filtration barriers?
The filtration barrier prevents molecules larger than 7 nm in diameter or those having a molecular mass equal to or greater than 40,000 daltons from passing through. Albumin = 7nm in diameter.
What happens to small proteins that slip into the filtrate despite the filtration barriers?
The small proteins that do slip into the filtrate are picked up by the proximal tubule by receptor-mediated endocytosis, then degraded into constituent amino acids that are returned to the blood resulting protein free urine.
For each of the following explain the effect on (Glomerular hydrostatic Pressure) GHP and GFR? Vasoconstriction of the afferent arteriole Vasoconstriction of the efferent arteriole Vasodilation of the afferent arteriole Vasodilation of the efferent arteriole
Vasoconstriction of the afferent arteriole = decreases GHP and GFR Vasoconstriction of the efferent arteriole = Increases GHP and GFR Vasodilation of the afferent arteriole = Increases GHP and GFR Vasodilation of the efferent arteriole = decreases GHP and GFR
Explain Tubuloglomerular Feedback mechanism for controlling GFR?
When NaCl is decreased it is sensed by the Macula Densa which then causes Renin secretion and decrease resistance to blood flow in the afferent arterioles. This is a negative feeback system that stabilizes renal blood flow and GFR.
What is the function of the renin-angiotensin-aldosterone system?
When blood flow or blood pressure in the afferent arteriole decreases for any reason, the renin-angiotensin-aldosterone triad is stimulated to compensate. Renin (Kidney) is an enzyme that cleaves angiotensinogen (produced in the liver) to form angiotensin (ANG) I in the blood. Angiotensin I is converted to Angiotensin II by ACE in the lung. Angiotensin causes systemic vasoconstriction and stimulates the secretion of aldosterone (increases the reabsorption of sodium and water to increase blood volume and BP)
Give an example of renin-blocking drugs?
beta-adrenergic blocking drugs They reduce blood pressure if it is thought that the renin-angiotensin-aldosterone system is a causative factor in a Pts. hypertension. ACE inhibitors can also reduce blood pressure.