Gfr And Renal Hemodynamics

Front 1

Components of the glomerular filtration barrier

Back 1

endothelial lining of the capillary loop, glomerular basement membrane and the slit diaphragm of the podocytes

Front 2

2 characteristics of the glomerular barrier that make it highly specialized

Back 2

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.

Front 3

The glomerular ultrafiltrate that enters the Bowman's Space is an ultrafiltrate of

Back 3

Plasma that contains no RBCs or albumin or other proteins.

Front 4

Minimal Change Nephropathy

Back 4

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.

Front 5

Hematuria of Glomerular Origin

Back 5

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.

Front 6

Glomerular Filtration

Back 6

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.

Front 7

How does the concentration of small molecules and ions in the filtrate compare to that of the plasma?

Back 7

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.

Front 8

Approx how much of the blood that flows through the glomeruli is filtered? How is this related to GFR?

Back 8

20%, menaing GFR in an adult human is approx 125 mL/Min or 180L/day

Front 9

Flow accross the capillary membrane is governed by

Back 9

Starling forces of Hydraulic and Oncotic P's and the intrinsic permeability of the membrane surface-hydraulic conductivity or ultrafiltration coefficient Kf

Front 10

Kf

Back 10

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

Front 11

Hydraulic Pressure in the glomerular capillaries vs systemic capillaries

Back 11

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

Front 12

Unique structural differences of the glomerular capillary

Back 12

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.

Front 13

Whatprevens a drop in hydrostatic pressure along the length of the capillary in the kidney

Back 13

the location of the capillary bw 2 high resistance arteriloes prevents a drop in hydrostatic P

Front 14

Pgc

Back 14

glomerular hydrostatic P
usu around 55mmHg
Net Pgc is Pgc- Pbs

Front 15

Pbs

Back 15

hydrostatic P in bowmen's space. Usu about 15 mmHg

Front 16

Plasma oncotic P at the beginning of the glomerular capillary is

Back 16

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

Front 17

Colloid Osmotic P

Back 17

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)

Front 18

SNGFR=

Back 18

Kf ((Pg-Pbs)-COP)

Front 19

Unique difference between glomerular capillaries and systemic capillaries are:

Back 19

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.

Front 20

In order for fluid to be reabsorbed as in the venular end of the peripheral capillary...

Back 20

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

Front 21

Qa

Back 21

Affarent glomerular capillary flow. usu 600mL/min ( equal to renal plasma flow)

Front 22

GFR

Back 22

Glomerular Filtration rate. Usu 120 mL/min or 180 L/day

Front 23

Qe

Back 23

efferent glomerular plasma flow. usu 480 mL/min

Front 24

Ratio of GFR to Qa

Back 24

Filtration Fraction. usu .2

Front 25

Tubular resorption rate

Back 25

99.5% of amount filtered.
Peritubular capillaries must resporb 99.5% of the fluid filtered thrgouh glomeruli

Front 26

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

Back 26

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.

Front 27

Clearance concept and Inulin

Back 27

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

Front 28

Clearance of any substance Z is =

Back 28

excretion rate of the substance divided by the plasma level of the substance

C= UzV/Pz mL/min

Front 29

Problems with inulin

Back 29

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

Front 30

Creatinine as a GFR marker

Back 30

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.

Front 31

Estimating GFR in males and females

Back 31

males: (140- age)x weight (kg)/ (serum creat in mg/dL x 72)

females: value for males x .85

Front 32

MDRD Formula for eGFR

Back 32

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.

Front 33

Is the clearance of inulin and other substances neither secreted or reabsorbed by the tubules affected by urine flow rate?

Back 33

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

Front 34

Is the clearance of urea affected by urine flow?

Back 34

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.

Front 35

The clearance of a substance that has been filtered and resorbed will always be what in relation to inulin

Back 35

clearance will always be LESS than inulin

Front 36

The clearance of a substance filtered and secreted, but not resorbed will always be what in relation to inulin?

Back 36

clearance will be greater

Front 37

Total renal blood flow in human (in both kidneys) is approx

Back 37

1100 ml/min

Front 38

2 ways to measure renal blood flow

Back 38

Electromagnetic or Doppler Flow probe, or Clearance of a flow dependent substance.

Front 39

EM or Doppler Flow Probe

Back 39

most accurate measurement of renal flow. Probe is a device that senses electrical changes produced by blood as it flows through a vessel.

Front 40

Clearance of a flow dependent substance (measuing renal blood flow)

Back 40

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.

Front 41

Where are the two largest hydrostatic pressure drops along the glomerular capillary?

Back 41

100 to 60 from arteriole to afferent end of the glomerular capillary
60-20 across efferent end of the arteriole

Front 42

Ra and Re

Back 42

Afferent Resistance- 35-45% of the total
Efferent resistance- 43-50% of the total

Front 43

Major driving force of glomerular filtration

Back 43

maintenance of high P in the glomerular capillaries

Front 44

Glomerular P is a function of

Back 44

the ratio bw Ra and Re

Front 45

Glomerular P can be regulated independantly of systemic P and Q bc

Back 45

Afferent and Efferent resistances are in series and can be regulated independantly and glomerular P is a fxn of Ra and Re

Front 46

What happens to RBF and GFR if Ra incr/decr?

Back 46

Ra incr = decr RBF and decr GFR
Ra decr= incr RBF and incr GFR

Front 47

What happens to RBF and GFR is Re incr/decr?

Back 47

Re incr= decr RBF and incr GFR
Re decr= incr RBF and decr GFR

Front 48

Renal Arteriolar Constrictors

Back 48

Adenosine, Angiotensin II, Endothelin, Norepi

Front 49

Renal Arteriolar Dilators

Back 49

Bradykinin, NO, prostaglandins

Front 50

Autoregulation of RBF and GFR

Back 50

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.

Front 51

When MAP drops below the atureg range, what happens to GFR anf RBF?

Back 51

they both drop drammatically--considder hypotension and acute RF

Front 52

Two main mechanisms responsible for autoreg of RBF and GFR

Back 52

Myogenic mechanisms and Tuboglomerular feedback

Front 53

Myogenic Mechanisms

Back 53

variations in the distension pressure of the afferent arteriole cause an opposite response from the smooth muscle in the arteriolar wall.
Transmural P theory-

Front 54

Tubuloglomerular feedback

Back 54

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

Front 55

Macula Densa

Back 55

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

Front 56

Prostaglandins

Back 56

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