Glomerular filtration Flashcards
1
Q
Overview of glomerular filtration
A
- Filtrate should be RBC free and protein free
- Plasma proteins are negatively charged, and the glomerular barrier (endothelial cell surface and basement membrane) are both negatively charged
- This, along w/ size selectivity from BM and podocytes leads to exclusion of proteins from the ultra filtrate
- GFR should be 120ml/min, which is 20% of plasma (80% continues in blood thru peritubular capillaries)
2
Q
Size and charge selectivity
A
- Size selectivity from BM and podocytes
- Charge selectivity from endothelial surface, BM, and podocyte surface
- There is greatly reduced filtration of large negatively charged particles (plasma proteins)
- Cationic and neutral particles are completely dependent on size, smaller ones are preferentially filtered
3
Q
Filtration forces 1
A
- Glomerulus resides btwn two arterioles (afferent and efferent), thus the pressure difference btwn these arterioles is negligible
- This keeps hydrostatic pressure high in the glomerulus to drive filtration
- Filtration pressure is the sum of hydrostatic pressure of capillaries (constant throughout capillary bed) and bowman’s space (constant), and bowman’s space oncotic pressure and capillary oncotic pressure (lower near afferent side, higher near efferent side)
4
Q
Filtration forces 2
A
- This means that the only factor changing is the capillary oncotic pressure, which increases as you move from afferent -> efferent since there is a higher concentration of albumin (losing fluid but maintaining protein)
- This pressure antagonizes filtration, thus more filtration occurs early in the capillary bed than later
5
Q
Peritubular capillaries
A
- The pressure is relatively constant in these capillaries, to allow for somewhat constant blood flow and adequate reabsorption
- 2/3 of filtrate reabsorbed in PT
6
Q
Changing filtration forces
A
- Glomerular capillary pressure (function of afferent and efferent arteriole resistance): constricting afferent arterioles lead to decrease in RBF and GFR
- Constricting efferent arterioles leads to increase/maintains GFR but reduces RBF
- Glomerular capillary filtration coefficient (Kf): represents the area and permeability of the glomerulus, can be changed by contraction of mesangial cells (SNS or ATII)
- Capillary oncotic pressure can change from changes in protein synthesis
7
Q
Role of SNS and ATII in arterioles and glomerulus
A
- SNS activity and ATII have the same effects
- They both increase Ra and Re (constrict both arterioles), and decrease Kf (contraction of mesangial cells)
- ATII constricts both but favors constriction of the efferent arteriole
8
Q
Mechanisms of maintaining Ra
A
- Ra is factor under most control, it will determine RBF and GFR
- Myogenic mechanisms and tubuloglomerular feedback (TGF) are the primary control mechanisms
9
Q
Myogenic control
A
- Intrinsic property of SMCs to contract when stretched
- When there is increased perfusion pressure of the afferent arteriole (increased stretch) the arteriole will constrict to normalize flow rate and maintain GFR
- When perfusion pressure drops the arteriole will relax to maintain GFR
10
Q
TGF 1
A
- Juxtaglomerular apparatus (JGA) links the distal TAL w/ the glomerular vascular pole
- Macula densa cells (MDCs) located at the JGA sense the transport of NaCl by NKCC and NHE from the filtrate to the ISF
- The overall goal is to keep NaCl and volume delivery to the distal nephron relatively constant for fine tuning in the collecting ducts
- If NaCl delivery is above normal the JGA will send signals (adenosine) to constrict the afferent arteriole to reduce GFR and normalize NaCl flow to MDCs (also contracts mesangial cells)
11
Q
TGF 2
A
- If NaCl transport is below normal (as in decreased ECF) TGF will dilate the afferent arteriole to allow for more GFR and NaCl to MDCs
- This is usually over-rode by ATII which will constrict the afferent arteriole, but mostly constricts efferent arteriole
- Additionally, when NaCl transport is low, MDCs will send signals to the afferent arteriole cells to increase production and release of renin
- RAAS is activated which will try to correct the ECF volume/BP (elevate it) by increasing Na reabsorption along the nephron
- TGF only affects afferent arteriole
- Overall: high NaCl leads to afferent and mesangial contraction to normalize GFR
- Low NaCl leads to afferent and mesangial relaxation and renin release (ATII constricts mostly efferent)
12
Q
Stimuli that increase NaCl at MDCs
A
- Increasing arterial BP leads to a decrease of NaCl reabsorption in PT leading to more NaCl in MCDs and TGF to stimulate reduction in RBF and GFR (bad for long term HTN when you want to have higher GFR to clear more fluid from the body)
- Increased GFR leads to more NaCl (more filtration) at MDCs, TGF will decrease GFR
- Anything that decreases NaCl reabsorption in PT or TAL will increase NaCl deliver to MDCs and leads to TGF reducing GFR
- Exception: loop diuretics will prevent NaCl reabsorption but will not stimulate TGF b/c they block the NKCC so the MDCs cannot sense the increase in Na
13
Q
Details of TGF detection and signal transduction
A
- Besides detecting NaCl thru NKCC/NHE, the MDCs may also sense volume flow thru deflecting of cilia on apical surface
- Cell swelling can also be detected, since NaCl entry is faster than NaCl exit
- Communication w/ MDCs and afferent arterioles is thru ATP and adenosine release, which causes SMC contraction to decrease RBF and normalize GFR
14
Q
Responses during hemorrhage: RAAS
A
- RAAS: stimulated due to baroreceptors, myogenic, and TGF
- Constricts arterioles everywhere to keep BP up
- ATII will preferentially constrict efferent arteriole to maintain GFR while RBF is reduced (but will also constrict afferent arteriole)
- Stimulates thirst, salt appetite, vasopressin release to restore ECF volume
- ATII and aldosterone stimulates NaCl reabsorption along nephron to increase ECF volume
15
Q
Responses during hemorrhage: SNS
A
- Stimulated by baroreceptors, leads to constriction of arterioles everywhere and increase HR to keep BP up
- Increases renin release (RAAS effects)
