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Flashcards in Test 1 (Renal Blood Flow Lecture) Deck (39):
1

Renal Functional Unit

Nephron:
- Number DECREASES with Age

Composed of:
a) Glomerulus (Glomerular Capillaries): Filters Blood

b) Tubule: Converts Filtrate into Urine


- Both are surrounded by the Blind end of the Tubular Epithelium ... BOWMAN's CAPSULE (Glomerular Capsule)

- Space between Capsule and Glomerulus ... BOWMAN's SPACE

- Filtrate passes from Blood to Tubular System through this Space

2

Types of Nephrons

1) Superficial (Cortical)
- SHORT loop of Henle

- Surrounded by Peritubular Capillaries

2) Juxtamedullary
- LONG loop of Henle

- LONG EFFERENT ARTERIOLES which divided into specialized peritubular Capillaries called the VASA RECTA!!!!!

- The Vasa Recta function to CONCENTRATE URINE

3

Renal Blood Supply

- Approximately 20% of CARDIAC OUTPUT

- High Pressure is Glomerular Capillaries (about 60 m Hg) causes FILTRATION of Blood

- 1100 - 1300 mL filtered/ min which produces 125- 130 mL of fluid termed the GLOMERULAR FILTRATE

- Lower Pressure in the PERITUBULAR CAPILLARIES (about 13 mm Hg) permits FLUID REABSORPTION

- Pressure in BOTH Capillary beds can be regulated by RESISTANCE changes in AFFERENT and EFFERENT Arterioles

4

Renal Blood Flow

- Important in Regulation of Body Fluid Volume and solute concentration

- Oxygen consumption of Renal Tissue is HIGHER than that of the BRAIN (Related to the HIGH RATE of Active Na+ Reabsorption which drives the Na+/ K+ ATPase)

- Cortex receives most RBF, Medulla receives LESS via VASA RECTA

- RBF determined by Pressure Gradient between Renal Artery and Renal Vein divided by the VASCULAR RESISTANCE

5

Glomerular Filtration: First step in Urine Formation

- Plasma is filtered under pressure from Glomerular Capillaries into Bowman's Capsule

- Normally, Glomerular Filtrate is essentially FREE of BLOOD CELLS and PROTEINS, but otherwise Identical to Plasma

- Glomerular Filtrate is HEAVILY MODIFIED as it passes down the Nephron

- Urine is very different from GLOMERULAR FILTRATE

6

Clinical Application of GFR

- Estimation of GFR is essential in assessment of Renal Function

- TOTAL GFR is the sum of the Filtration Rate in all functioning Nephrons and therefore is an INDEX of FUNCTIONING RENAL MASS

- GFR estimate can be used to evaluate the severity and course of RENAL DISEASE

- A fall in GFR indicates disease Progression (Most often resulting from a DECREASE in NET PERMEABILITY due to LOSS of FILTRATION SURFACE AREA)

- A Rise in GFR is indicative of at least PARTIAL RECOVERY

7

Glomerular Membrane: A Molecular Sieve

- Free passage of Water, Small Solutes (Glucose, Amino Acids, Electrolytes): concentration are the same on BOTH SIDES of MEMBRANE

- Passage of LARGE Molecules (Proteins) and formed elements is impeded

- Normally, only VERY SMALL amounts of Protein are filtered into BOWMAN'S Capsule

8

Structure of Glomerular Membrane

Three Distinctive Layers:
1) FENESRTATED CAPILLARY ENDOTHELIUM:
- Highly permeable to WATER, Dissolved Solutes

2) GLOMERULAR BASEMENT MEMBRANE:
- Collagen, Proteoglycans contain Anionic (NEGATIVE) Charges

3) PODOCYTE EPITHELIUM:
- Slit pores between Podocytes RESTRICT LARGE Molecules

9

Proteins of Glomerular Slit Diaphragm CD2AP and CD2- associated Protein

- CD2AP

- NEPHRIN Molecules

10

Mechanism of Filtration

- Based on size and Charge of Macromolecules:
a) LARGE Molecules are RESTRICTED more than Smaller

b) ANIONIC Molecules are RESTRICTED more than Neutral or Cationic

11

Clinical Application of Filtration

- Some kidney disease cause LOSS of NEGATIVE CHARGE on the basement membrane before noticeable changes in RENAL STRUCTURE

Minimal Change Disease or Neuphropathy:
- Results in FILTRATION of Proteins (Especially ALBUMIN) and their appearance in Urine (Albuminuria or Proteinuria)


- More extensive Renal Injury often results in LARGE amount of PROTEIN in URINE

12

Physical Forces affecting Glomerular Filtration

- GFR is remarkably HIGH (125 ml/ min, 180 L/ day)

GFR is a product of 3 Physical Factors:
1) HYDRAULIC CONDUCTIVITY (Lp) of Glomerular Membrane
- Permeability or Porosity of Capillary Wall

2) SURFACE AREA for Filtration (2m^2)
- Product of 1 and 2 is ULTRAFILTRATION COEFFICIENT Kf

3) Capillary Ultrafiltration Pressure (Puf)




GFR = Kf x Puf

13

Mechanisms for Altering GFR

GFR = Kf x Puf

1) Altered Kf:
- MESANGIAL CELL Contraction

2) Alrered Puf:
- Changes in P(Gc)


P(Gc) Determined by 3 Factors:
1) Renal Arterial Blood Pressure

2) Afferent Arteriolar Resistance

3) Efferent Arteriolar Resistance

14

Glomerular Mesangial Cells can alter Kf

GLOMERULAR MESANGIAL CELLS (M) located within Glomerular Capillary Loops

- Contraction of Mesangial Cells SHORTENS CAPILLARY LOOPS, LOWERS Kf, and thus LOWERS GFR!!!!!!!!

15

Ultrafiltration Pressure: Driving force for Glomerular Filtration

- Puf is determined by HYDROSTATIC and COLLOID OSMOTIC PRESSURES in Glomerular Capillaries

Bowmans' Capsule:

Puf = P(Gc) - (P(Bc) + p(Gc))

16

Glomerular Filtration

- Depends on NET FILTRATION PRESSURE!!!!!

Puf = P(Gc) - (P(Bc) + p(Gc))

17

Glomerular and Peritubular Capillary Starling Forces

1) Glamerular Capillary:
- At the AFFERENT Arteriole the Capillary Hydrostatic pressure is GREATER than the Plasma Oncotic Pressure and Capsular Hydrostatic pressure combined which means there is a NET FILTRATION!

- At the EFFERENT Arteriole the Capillary Hydrostatic pressure is EQUAL to the Plasma Oncotic Pressure (It has INCREASED) and the Capsular Hydrostatic Pressure combined which means there is NO NET MOVEMENT


2) There will be a HIGHER GFR when the RBF is HIGHER!!!


3) Peritubular Capillary:
- At the EFFERENT Arteriole the Plasma Oncotic Pressure is much HIGHER than the Capillary Hydrostatic Pressure which means there is a NET REABSORPTION!!!

- At the Venous End, the Plasma Oncotic Pressure is only slightly higher than the Capillary Hydrostatic Pressure which means there is still a NET REABSORPTION but it is not as great as the Efferent Arteriole

18

Glomerular and Peritubular Capillary Starling Forces Explination

1) In normal individuals, GFR is primarily regulated by ALTERATION in PGc

2) PGc is determined by changes in SYSTEMIC Arterial Pressure (PA), Afferent Arteriolar Resistance (RA), and Efferent Arteriolar Resistance (RE)

19

Key Concepts of GFR

Control of GFR by adjusting RESISTANCE of Afferent and Efferent Arterioles:

1) AFFERENT Arteriolar Constriction:
- Greater Pressure drop UPSTREAM of GLOM Capillaries

- PGc falls, which LOWERS GFR

- Renal Blood flow falls due to INCREASE in Resistance

2) EFFERENT Arteirolar Constriction:
- Pooling of Blood in Glomerular Capillaries

- Increase PGc INCREASES GFR

- Renal Blood Flow would DECREASE!!!!

20

Garden Hose Analogy

1) Increased Systemic Arterial Pressure
- Causes an INCREASE in GFR!!!

2) Afferent Arteriolar Constriction
- Decreases the GFR and the RBF

3) Efferent Arteriolar Constriction
- The GFR will INCREASE and the RBF will go DOWN!!!

21

Effects on Afferent and Efferent Arteriolar Constriction on RPF and GFR

1) AFFERENT Constriction
- GFR will Decrease
- RPF will Decrease
- PGc will Decrease

****GFR Decreases because both Glomerular Capillary Pressure and Renal Plasma Flow fall

2) EFFERENT Constriction
- GFR will Increase and then plates
- RPF will Decrease
- PGc will INCREASE

***GFR INCREASES because rising Capillary pressure dominates

***GFR DECREASES because falling RPF Dominates


3) Dilation of Efferent Arteriole:
- Decrease the GFR

4) Dilation of Afferent Arteriole:
- Increase the GFR

22

Hydrostatic Pressures in Renal Microcirculation: Effects of Arteriles Constriction

1) The largest Decrease in Hydrostatic Pressure when there is Afferent Arteriolar constriction is in the AFFERENT Arteriole

2) The largest Decrease in Hydrostatic Pressure when there is Efferent Arteriole constriction is in the EFFERENT Arteriole

23

Renal Blood Flow

- Regulated by several mechanisms in order to CONTROL GFR

- Vascular Resistance to RBF is primarily determined by AFFERENT and EFFERENT Arterioles

- Controlled y SYMPATHETIC Nervous System (NE) and various Hormones along with INTERNAL (Myogenic, T-G Feedback) control mechanisms

- GFR is strictly regulated over a MAP range between 80 to170 mm Hg via a process called AUTOREGUALTION!!!!!!!

24

Effects of Sympathetic Stimulation

1) Constriction of Afferent and, to a lesser extent, Efferent Arterioles:
- DECREASE in RBF and GFR

- Diverts the Renal Fraction to VITAL ORGANS

2) Increased RENIN Secretion by Granular Cells

3) Angiotensin II thus produced restores BLOOD PRESSURE (Systemic Vasoconstriction)

4) Angiotensin II promotes Arteriolar Constriction (Efferent > Afferent):
- Raises Blood Pressure

- May stabilize GFR (Moderate Ang II)

5) Stimulate Na+ Reabsorption in Proximal Tubule, Thick Ascending limb of Henle's loop, Distal Convoluted Tubule, Collecting Duct

25

Renal Prostaglandins dampen Vasoconstriction by Angiotensin II and Sympathetic Activity

- Release of Prostaglandins enhanced by ADH

26

Control of GFR and RBF

1) Norepinephrine:
- Decreases GFR

2) Epinephrine:
- Decreases GFR

3) Endothelia:
- Decreases GFR

4) Angiotensin II:
- Normal GFR (Prevents a Decrease)
- Clamps down on the Efferent Arteriole

5) Endothelial-derived Nitric Oxide
- Increases GFR

6) Prostaglandins
- Increases GFR

27

Substances Affecting Vascular Smooth Muscle in renal Arterioles

1) Nitric Oxide and Prostaglandins (PGI2, PGE2) cause VASODILATION

2) Endothelia and Angiotensin II cause VASOCONSTRICTIOn
- ACE Inhibitors will cause for the Vasoconstriction to stop because they INHIBIT Ang I from converting into Ang II

28

Effects of Changes in Starling Forces of GFR and RBF

1) Vasodilate Afferent Arteriole (Prostaglandins E2 and I2, Bradykinin, NO, Dopamine, ANP)
- INCREASE in RBP
- INCREASE in GFR

2) Vasodilator Efferent Arteriole (ACE Is, ARBs)
- DECREASE GFR

3) Constriction of Afferent Arteriole (Sympathetic)
- DECREASE RBP
- DECREASE GFR

4) Constriction of Efferent Arteriole (Ang II)
- Normal or INCREASE in GFR

29

Auto-regulation

- The kidney filtrates carefully

- This is accomplished by the Glomerulus being situated between 2 arteriolar beds. Vascular tone in these two beds:
1) Protects the delicate Glomerular architecture at times of High Blood Pressure

2) Preserves GFR at times of LOW SYSTEMIC Blood Pressure

30

Auto regulation of RBF and GFR

- Process whereby RBF an GFR are maintained constant regardless of marked changes in Blood Pressure by adjustments of Afferent and Efferent Resistance

- Also allows for STRICT CONTROL of Water and Solute levels

- Effective range of Control is between approximately 75 - 160 mm Hg

- Without Autoregulation, a small increase in Blood Pressure would result in Large Increases in fluid RETENTION and VOLUME DEPLETION

31

Mechanisms of Autoregulating Renal Blood Flow and GFR

1) MYOGENIC Responses to:
- INCREASES Systemic Arterial Pressure

2) TUBULOGLOMERULAR FEEDBACK response to:
- Increased GFR

- Decreased GFR

32

Myogenic Mechanism of Autoregulation

- Mechanism to maintain RBF and GFR

- Resistance of Blood Vessels to Stretch when exposed to High Aterial Pressure

- Via CONTRACTION of Vascular Smooth Muscle in response to STRETCH with INCREASED movement of Ca++ into cells

- Prevents INCREASE in RBF and GFR when BP is HIGH

33

Tubulogloermural Feedback

- TUBULOGLOMERULAR FEEDBACK: Autoregulation of GFR by the rate of fluid NaCl delivery to the MACULA DENSA. Feeds back to the Kidneys to control Renal Afferent and Efferent Arteriolar Resistance

- This process is regulated by the JUXTAGLOMERULAR APPARATUS (JGA) which consists of the MACULA DENSA Cells in the DISTAL TUBULE and the JUXTAGLOMERULAR Cells in the Walls of the AFFERENT and EFFERENT Arterioles

- The MACULA DENA Cells sense NaCl concentration in the DISTAL TUBULE

- Feeds this information back to the JG Cells to adjust Arteriolar Resistance

- Ensure constant delivery of Na+ to Disal Tubule and prevents changes in RENAL EXCRETION

- RENIN release is also regulated here

34

Tubuloglomerular Feedback involving Juxtaglomerular Apparatus (JGA)

Components of JGA:
1) MACULA DENSA: In wall at beginning of Distal Convoluted Tubule

2) EXTRAGLOMERULAR MESANGIAL CELLS
- Aka Lacis Cells

3) JUXTAGLOMERULAR (Granular) CELLS
- In Afferent and Efferent Arteriole Smooth Muscle


- JGA responds to Blood Pressure changes to maintain GFR nearly CONSTANT!!!!!!

35

TGF Response to Increased Renal Perfusion Pressure

Tubuloglomerular Feedback (TGF) response to INCREASED Renal Perfusion Pressure:
- Results in CONSTRICTION of AFFERENT Arteriole with a fall in GFR


*** ADENOSINE mediates VASOCONSTRICTION at the AFFERENT Arteriole in response to Tubuloglomerular Feedback

36

TGF response to Decreased Renal perfusion Pressure

- GFR FALLS due to effective Circulating Volume depletion (GI Fluid Losses, CHF): results in less Na+, Cl- filtered and delivered to MACULA DENSA

- Local Responses which may be mediated via NO will cause AFFERENT Arterioler DILATION

- MACULA DENSA signals Granulat Cells to secrete RENIN

- Increased circulation Angiotensin II:
a) Potent Vasoconstrictor that restores Blood Pressure

b) Efferent Arteriolar Vasoconstriction:
1) Moderate: Minimizes fall in GFR

2) Severe: GFR falls due to stagnant Blood Flow

37

Clinical Application of Glomerular Disease

- Primary Glomerular disease will tend to LOWER GFR (Most often resulting from a Decrease in net permeability due to LOSS of FILTRATION SURFACE AREA)

- Autoregulatory response will response by:
1) More Na+ Reabsorbed
2) Efferent Arteriole Constriction
3) This will put more pressure on Kidneys that aren't working properly and try to Increase the GFR when it cant!

38

Clinical Application Renal Artery Stenosis

In a patient with hypertension Secondary to Renal Artery Stenosis, what would happen to GFR in the Stenotic Kidney as Blood Pressure is lowered with an ACE Inhibitor (Which Decreases formation of Angiotensin II)?

1) Blood Flow has decreased because of the Stenosis

2) The GFR has Decreased and so has the RBF

3) SYMPATHETIC Nervous System will be activated

4) Renin will then be released

5) Na+ RETENTION is Increased

6) Ang II CONSTRICTS the Efferent Arteriole to Maintain GFR

**Make sure the patent is not taking an ACE Inhibitor when having Renal Artery Stenosis because this will DAMAGE the KIDNEYS!!!

39

Summary: Glomerular Filtration

- Molecular sieving by Glomerular Membrane

- Physical determinants of GFR: Kf x Puf

- Control of Puf by Afferent, Efferent Arterioles

- Autoregulation of Renal Blood Flow, GFR:
a) Myogenic Mechanism

b) Tubuloglomerular Feedback

- Renal Prostaglandins: Protective Vasodilators