Renal BF and Glom Filtr-Rao Flashcards
Functions of the kidney? (5)
- Ridding the body of metabolic by-products (urea, creatinine, uric acid, sulfate, phosphate) 2. Excrete toxins and foreign substances (medications, diet) 3. Ability to balance daily intake of salt and water with their excretion in the urine. 4. Acid base balance 5. Endocrine functions (EPO production, conversion of Vit D3 to calcitrol)
A functional kidney is crucial for the maintenance of ___________.
body homeostasis
How can renal failure lead to death? (steps)
Renal Failure–> Loss of ability to balance salt and water–> Edema (retention of fluid)–> Increased work load of heart–> Heart failure and pulmonary edema (these can be complicated by hyperkalemia or acidemia)–> death
What is End-stage renal disease? Treatment?
little or no kidney function, cannot survive without hemodialysis or kidney transplant
What is the functional unit of the kidney? How many per kidney?
Nephron; nearly 1 million per kidney
What are the two types of nephrons and their relative frequencies?
- Cortical (Superficial) 85%
2. Juxtamedullary 15% (these extend all the way into the inner medulla)
The kidney receives how much of the body’s cardiac output?
20%
What is unique about the vasculature structure kidney/nephron?
There are two sets of capillaries
Path of blood in the kidney?
RA–Interlobar aa–Arcuate aa–Radial/Interlobular aa–Afferent Arteriole–Glomerular capillary bed– Efferent Arteriole– Peritubular capillary bed– Renal V
The afferent arteriole forms what? The efferent arteriole forms what?
Aff– Glomerular cap bed
Eff– Peritubular cap bed
In JM nephrons, what supplies blood to the medullary region?
Vasa recta
Due to the unique structure of the renal vasculature, what is very different than very different compared to vasculatures elsewhere in the body?
The Vascular Pressure Profile is very different.
What about the vascular pressure profile is different in the renal vasculature?
The arteriovenous pressure drop occurs in 2 steps (unique to this organ), maintaining high hydrostatic pressure in the glomerular capillary. (Look at graph and diagram–resistance in aff and eff arterioles with low resistance in glom capillaries)
Describe the Oncotic pressure throughout the renal vasculature?
The oncotic pressure is steady/constant, then gradually increases in the glomerular capillaries bc of filtration, and then it lowers back down to normal (~20) by the time it reaches the renal vein (look at graph)
What are the three processes that occur in the nephron that contribute to urine formation?
- Glomerular Filtration
- Tubular Reabsorption
- Tubular Secretion
What are the four different types of substances that can filter into the tubules?
- Freely filtered, not reabsorbed or secreted (inulin)
- Freely filtered, partly reabsorbed, not secreted (urea)
- Freely filtered and completely reabsorbed (nutrients–glc, organic acids)
- Freely filtered, not reabsorbed but secreted from tubules
What is the summary equation of urinary excretion?
Excretion = Filtration-Reabsorption+Secretion
Why is it useful to filter large amounts of body fluids and solutes and reabsorb most of them back into the body? (2)
- Allows kidneys to rapidly remove waste products from the body that depend primarily on glomerular filtration for excretion
- Allows all body fluids to be filtered and processed several times each day.
(kinda 3. quickly remove products that are continuously made thruout the day.
Compostition of filtrate (vs. plasma)?
A. Similar to plasma but without large proteins (almost no albumin, globulin, or Hgb)
B. Low level of some small molecules bound to proteins (calcium and fatty acids)
C. 4-5% more anions and 4-5% less cations (due Gibbs Donnan Effect–cations stay in plasma, anions go due to attraction vs repulsion effect of the large negatively charged proteins in the plasma)
What is the average GFR? What are two things that cause the GFR to decrease?
average GFR= 130ml/min (180L/day)
GFR decreases with age and renal disease
What is the filtration fraction?
FF= GFR/RPF= 130/670= 19.4% on average
How do factors that affect GFR and RPF affect FF?
a. Factors that reduce GFR reduce FF (uretral obstruction)
b. Factors that reduce RPF increase FF (renal artery stenosis)
What are the three filtration barrier of the glomerulus?
- Capillary endothelium (much leakier than capillaries of other organs)
- Basement Membrane (just below the endothelial monolayer, its a clear meshwork of collagen and proteoglycan fibrils–has a negative charge)
- Epithelium or Podocyte monolayer (extend pedicels, forming slit pores; the major barrier of proteins)
What two factors affect the filterability of solutes?
- Size selectivity (glomerular pores=8nm/80Angstroms)
2. Charge selectivity
If albumin is small enough to fit thru pores (6nm/60Ang) why is it not normally filtered?
It is prevented by charge selectivity due to its negative charge
What are the determinants of GFR?
GFR= Kf x Net FIltration Pressure
What does Kf represent and what is its normal value?
Kf=Filtration Coefficient= Hydraulic conductivity x SA of glomerulus
Normally Kf= 0.08 nl/s-1mmHg
How does diabetes mellitus affect Kf?
Reduced Kf; increased thickness of BM and damaged capillaries
How does Net Filtration Pressure in glomerulus compare to other capillaries?
It is 400x greater (=12.5 in glom cap)
Factors favoring filtration pressure?
Glomerular hydrostatic pressure (P-G)
Bowman’s space oncotic pressure (π-BS)
Factors opposing filtration?
Glomerular oncotic pressure (π-G)
Bowman’s space hydrostatic pressure (P-BS)
Equation for Net Filtration Pressure?
NFP= (P-G+π-BS) - (π-G+P-BS)
How is net filtration pressure regulated?
A. Changes in the glomerular hydrostatic pressure by changing resistance (Rt) in aff or eff arterioles)
B. Changes in Bowman’s Space Hydrostatic pressure (P-BS)
C. Changes in capillary oncotic pressure (π-G)
What happens when: (look at diagram) A) Equal resistance in aff and eff arterioles? B) Higher afferent Rt? C) Higher efferent Rt? Look at summary slide
A) Constant P-G at 60 mmHg and GFR
B) Reduced P-G; therefore, reduced GFR
C) HIgh P-G; therefore, increased GFR (may be normalized by increased π-G)
Affects of changing afferent resistance on GFR and RPF?
a. Increased aff Rt: both GFR and RPF decrease
b. Decreased aff Rt: both GFR and RPF increase
Affects of changing efferent resistance on GFR and RPF?
a. Increased eff Rt: GFR increases, RPF decreases
b. Decreased eff Rt: GFR decreases, RPF increases
P-BS=?
resistance of nephron and the rate of urine flow
How does obstruction of the lower urinary tract (kidney stone, tumor, hypertrophic prostate) affect GFR?
it increases P-BS, leading to reduced net filtration pressure, and therefore, reduced GFR
How does frequent emptying of the bladder affect GFR?
Can decrease P-BS, leading to increased net filtration pressure, and therefore, increased GFR
What causes π-G changes?
a) change in protein concentration in the glomerular capillary blood; b) reduced RPF (with GFR corrected by autoregulation)
How does reduced RPF affect π-G and GFR?
low capilary flow→ increased FF→increased π-G→ reduced NFP → reduced GFR
What is autoregulation of GFR? How is it affected by systemic influences?
A phyiologic mechanism that maintains constant GFR (and RPF??) (via renal vascular resistance changes) in the face of changes in mean arterial pressure, venous pressure, obstructions, etc.; it is independent of systemic influences bc it occurs in isolated kidney.
What would happen without autoregulation if arterial pressure increased 25%?
GFR would increase, and if reabsorption remained constant (175L/day), urine excretion (normally 1.5L/day) would increase, depleting the blood volume
What is the mechanism of autoregulation?
Intrinsic adjustment of renal vascular resistance to counter balance any extrinsic factor that would change RBF by mechanisms other than direct influence on renal vascular resistance itself.
What specifically is regulated in autoreg?
Afferent Arteriolar resistance!!!
How is the afferent arteriole (vascular tone) regulated/changed in autoregulation? (two mech’s)
- Myogenic Mechansim (questionable; direct stimulation of arteriolar sm muscles)
- Tubuloglomerular Feedback (TGF)
What system is responsible for tubuloglomerular feedback? What does it consist of? What is it in contact with?
Juxtaglomerular apparatus; composed of Macula Densa (MD) cells of distal tubule and juxtaglomerular (JG) cells of the afferent arteriole
How does TGF cause rapid change in the GFR at the level of a single nephron?
Changes in NaCl concentration in distal tubule fluid are sensed by MD cells, which results in changes of aff arteriole resistance, changing the GFR
What is the effect NaCl changes sensed by MD?
a) Higher NaCl at MD (distal tubule)→ increased aff arteriole Rt→decreased GFR
b) Low NaCl at MD→reduced aff arteriole Rt→increased GFR
What stimulates GFR autoreg?
a. changes in Chloride (NaCl) in distal tubule
b. Changes in GFR (fluid delivery to distal tubule)
What are three mechanisms of systemic regulation of GFR?
- RAAS
- Sympathetic NS regulation
- Hormonal regulation
What activates the RAAS?
Activated by reduced ECFV or Arterial BP leading to reduced P-G and GFR leading to reduced Cl sensed by MD cells
How does the RAAS respond?
JG cells (decreased intracell Ca2+) secrete Renin→AngI→AngII (activ’d by ACE in lung or kidney)→Aldosterone (from adrenal cortex)→Na and H2O retention
How else does ANGII contribute (other than aldosterone)?
It directly causes constriction of the arterioles (mostly afferent), increasing aff arteriole Rt, and therefore reducing GFR and P-G
How is GFR regulated by Sympathetic NS?
Renal blood vessels, including aff and eff arterioles are richly innervated by Symp fibers. Symp activation→constriction of aff arterioles→reduced RPF anf P-G→reduced GFR→Renin secretion and increased Na+ reabsorption
Under what conditions does SNS stimulation override autoregulation?
under low ECF volume
What 4 hormones regulate GFR?
Adrenaline and Endothelin-1 decrease GFR; NO and Prostaglandins increase GFR
How does adrenaline reduce GFR? How about Endothelin-1?
Adrenaline contricts arterioles (preferentially afferent)→reduced GFR
Endothelin-1 released from damaged endothelial cells→ constr of aff AND eff arterioles→reduced GFR
How do NO and PG’s regulate GFR?
they decrease vascular Rt, increasing GFR
What are two causes of proteinuria?
- Barrier Failure/Breakdown leading to filtration of albumin and cells
- Abnormal circulating proteins
Invisible vs. visible barrier breakdown?
a) Invisible: Loss of charge selectivity, leads to Nephrotic Syndrome
b) Visible: large pores, leads to Nephritic Syndrome
What are two causes of abnormal circulating protein?
- Breakdown of tissue
2. Production of abnormal protein by tumor cells
