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56 Cards in this Set
- Front
- Back
Components of the glomerular filtration barrier
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endothelial lining of the capillary loop, glomerular basement membrane and the slit diaphragm of the podocytes
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2 characteristics of the glomerular barrier that make it highly specialized
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1- the effective pore size excludes molecules larger than 42 A.
2- the slit diaphragm and podocytes are negatively charged (glycoprotein composition). So, molecules in the range of 20-40 A are selectively filtered as are cationic molecules more readily than anionic. |
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The glomerular ultrafiltrate that enters the Bowman's Space is an ultrafiltrate of
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Plasma that contains no RBCs or albumin or other proteins.
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Minimal Change Nephropathy
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loss of permselectivity properties of the GBM.
Characterized by fusion of the foot processes, loss of charge in the basement membrane and filtration slits, and loss of perselectivity properties of the GBM. Clinical findings include proteinuria (often greater than 3.5 Gm/d) Also may include edema and hypoalbinuria. |
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Hematuria of Glomerular Origin
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When RBCs and casts of RBCs are found in the urine sediment, disease of the glomerular capillary is confirmed and is denoted as "nephritic" syndrome.
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Glomerular Filtration
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separates the aqueous phase of plasma from the large proteins and formed elements, so the filtrate is relatively free of protein and absent cellular components such as erythrocytes.
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How does the concentration of small molecules and ions in the filtrate compare to that of the plasma?
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The concentration of the filtrate mirrors that of the plasma in regards to small particles and ions. The exception being drugs and substances that are bound to plasma proteins.
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Approx how much of the blood that flows through the glomeruli is filtered? How is this related to GFR?
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20%, menaing GFR in an adult human is approx 125 mL/Min or 180L/day
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Flow accross the capillary membrane is governed by
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Starling forces of Hydraulic and Oncotic P's and the intrinsic permeability of the membrane surface-hydraulic conductivity or ultrafiltration coefficient Kf
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Kf
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Ultrafiltration coefficient. Intrinsic permeability of the membrane surface or hydraulic conductivity.
Kf in the glomerular capillary is about 100-200x greater than in muscle and other tissues. This helps account for the very high water permeability of these capillaries |
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Hydraulic Pressure in the glomerular capillaries vs systemic capillaries
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Pressure is higher in the glomerular capillaries bc it is interposed bw two arterioles that provide resisitance. Hydraulic P is about 50-60 mmHg in the glomerulous while peripheral muscle avgs about 10-20mmHg
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Unique structural differences of the glomerular capillary
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In the kidney there are 3 layers instead of the usu 2. The capillary has an endothelium with fenestrations, a basement membrane, and then a layer of epithelial cells called podocytes. These 3 layers contribute to the filtration barrier.
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Whatprevens a drop in hydrostatic pressure along the length of the capillary in the kidney
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the location of the capillary bw 2 high resistance arteriloes prevents a drop in hydrostatic P
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Pgc
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glomerular hydrostatic P
usu around 55mmHg Net Pgc is Pgc- Pbs |
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Pbs
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hydrostatic P in bowmen's space. Usu about 15 mmHg
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Plasma oncotic P at the beginning of the glomerular capillary is
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22 mmHg. Therefore the net ultrafiltration pressure is:
Pgc-Pbs-plasma oncotic P 55-40-22=18mmHg=net ultrafiltration P at the beginning of the capillary |
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Colloid Osmotic P
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rises along the length of the capillary as water and electrolytes are filtered. Note that Ultrafiltration P declines in glomerular capillaries bc plasma oncotic P rises, NOT bc of a decrease in intracapillary hydrostatic P (systemic capillaries)
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SNGFR=
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Kf ((Pg-Pbs)-COP)
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Unique difference between glomerular capillaries and systemic capillaries are:
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1- glomerular capillaries have high hydraulic conductivity
2- Glomerular capillaries are located between two hi resistance arterioles which minimizes the pressure drop alond the length of the capillary. |
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In order for fluid to be reabsorbed as in the venular end of the peripheral capillary...
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hydrostatic P must fall below that of oncotic P. This occurs in the postglomerular peritubular circulation of the kidney, those capillaries which surround renal tubules
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Qa
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Affarent glomerular capillary flow. usu 600mL/min ( equal to renal plasma flow)
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GFR
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Glomerular Filtration rate. Usu 120 mL/min or 180 L/day
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Qe
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efferent glomerular plasma flow. usu 480 mL/min
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Ratio of GFR to Qa
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Filtration Fraction. usu .2
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Tubular resorption rate
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99.5% of amount filtered.
Peritubular capillaries must resporb 99.5% of the fluid filtered thrgouh glomeruli |
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Peritubular resorption is facilitated by two features of the renal circulation which cause conditions in the peritubular capillaries to be similar to the venular end of peripheral capillaries
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1- Peritubular Hydrostatic P is low bc it lies beyond the high resistance in the efferent arteriole
2- COP in the peritubular capillary blood is hi bc the blood is post glomerular. |
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Clearance concept and Inulin
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Measure the clearance of a substance that is filtered by the glomerulus but neither reabsorbed or secreted by the tubule. Prototype substance is inulin. Z=inulin
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Clearance of any substance Z is =
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excretion rate of the substance divided by the plasma level of the substance
C= UzV/Pz mL/min |
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Problems with inulin
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sterile solution must be infused at a constant rate and accurately timed urine collections made. Blood must be sampled to ensure steady state. Nveretheless--> it is the GOLD STANDARD
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Creatinine as a GFR marker
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Creatinine is an endogenous metabolite produced at a relatively constant rate unless big changes in muscle metabolism occur. Creatinine is excreted mostly but not totally, by glomerular filtration so its clearance is close to inulin's.
Ex: if GFR is reduced by 50% with constant production, serum creatinine will double. |
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Estimating GFR in males and females
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males: (140- age)x weight (kg)/ (serum creat in mg/dL x 72)
females: value for males x .85 |
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MDRD Formula for eGFR
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186 x (Pcr)^ -1.154 x (Age)^-0.203 x (.742 if female) x(1.210 if African American)
formula can help detect kidney disese much earlier. Pcr may not increase until GFR is <70 in many pts. |
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Is the clearance of inulin and other substances neither secreted or reabsorbed by the tubules affected by urine flow rate?
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no, bc the excretion rate is independant of the tubular reabsorption of water. BUT the concentration of inulin in the urin will of course vary with the urine volume.I
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Is the clearance of urea affected by urine flow?
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Yes. bc urea can be reabsorbed from the tubules and is afected by the rate of water reabsorption in the collecting ducts which affects the concentration gradient for diffusion of urea in the tubule and the contact time for back-diffusion. in this way, the ratio of creat to urea can serve as a rough clinical index of fluid filtration and reabsorption such as in dehydration or kidney failure.
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The clearance of a substance that has been filtered and resorbed will always be what in relation to inulin
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clearance will always be LESS than inulin
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The clearance of a substance filtered and secreted, but not resorbed will always be what in relation to inulin?
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clearance will be greater
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Total renal blood flow in human (in both kidneys) is approx
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1100 ml/min
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2 ways to measure renal blood flow
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Electromagnetic or Doppler Flow probe, or Clearance of a flow dependent substance.
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EM or Doppler Flow Probe
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most accurate measurement of renal flow. Probe is a device that senses electrical changes produced by blood as it flows through a vessel.
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Clearance of a flow dependent substance (measuing renal blood flow)
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Fick Method.
Flow(ml/min)= consumption (mg/min)/ (A-V) (mg/min) PAH is the most convenient marker. 2 assumptions: more substance delivered to the kidney= more removed and the amt of substance removed by the kidney can be accurately measured. |
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Where are the two largest hydrostatic pressure drops along the glomerular capillary?
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100 to 60 from arteriole to afferent end of the glomerular capillary
60-20 across efferent end of the arteriole |
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Ra and Re
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Afferent Resistance- 35-45% of the total
Efferent resistance- 43-50% of the total |
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Major driving force of glomerular filtration
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maintenance of high P in the glomerular capillaries
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Glomerular P is a function of
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the ratio bw Ra and Re
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Glomerular P can be regulated independantly of systemic P and Q bc
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Afferent and Efferent resistances are in series and can be regulated independantly and glomerular P is a fxn of Ra and Re
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What happens to RBF and GFR if Ra incr/decr?
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Ra incr = decr RBF and decr GFR
Ra decr= incr RBF and incr GFR |
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What happens to RBF and GFR is Re incr/decr?
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Re incr= decr RBF and incr GFR
Re decr= incr RBF and decr GFR |
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Renal Arteriolar Constrictors
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Adenosine, Angiotensin II, Endothelin, Norepi
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Renal Arteriolar Dilators
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Bradykinin, NO, prostaglandins
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Autoregulation of RBF and GFR
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occurs when incr or decr in perfusion P cause no change in GFR or RBF. Happens bw about 80 and 200 mmHg MAP. Autoreg can probably be attributed to changes in Ra in response to perfusion pressure changes.
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When MAP drops below the atureg range, what happens to GFR anf RBF?
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they both drop drammatically--considder hypotension and acute RF
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Two main mechanisms responsible for autoreg of RBF and GFR
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Myogenic mechanisms and Tuboglomerular feedback
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Myogenic Mechanisms
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variations in the distension pressure of the afferent arteriole cause an opposite response from the smooth muscle in the arteriolar wall.
Transmural P theory- |
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Tubuloglomerular feedback
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concept proposes that afferent arteriolar tone is determined by the production of a vasoconstrictorin the afferent arteriolar wall the release of which is controlled by the macula densa cells of the distal tubule
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Macula Densa
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segment of the distal convoluted tubule which contacts the afferent arteiole of its own glomerulus. Conjunction of the two structures is called the juxtaglomerular JG apparatus. Increases in the NaCl delivery to the MD cause release of the vasoconstrictor angiotensin
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Prostaglandins
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family of fatty acids produced in all blood vessels. PGI2 is produced in renal blood vessels, esp in the cortex, and that E series prostaglandins are produced in the medulla.
NSAIDS can block prostaglandins and therefore block vasodilation resulting in vasoconstriction and ARF |