Structure of Nephron, Renal Blood Flow, & Glomerular Filtration

Created by ojames03 Plus

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Features of The Kidney

1)Regulation of volume, osmolarity, & electrolytes
-->Regulates H2O balance, Na+/K+, Ca2+, EFC Volume
-->***ADH regulates OSMOLARITY
-->***Aldosterone regulates Na2+ & other electrolytes
2)Regulation of arterial blood pressure (by production of RENIN)
3)Regulation of blood pH (by excreting acid & reabsorbs HcO-3)
4)Regulation of RBC production
5)Activation of **Vitamin D** for CALCIUM BALANCE
6)Excretion of metabolic wastes & bioactive substances such as hormones, toxins (which are excreted), antigen, & drugs
-->Excretion occurs as Urea
-->Dialyzing machine can substitue for this function

Additional features of the Nephron

-->Represents the functional unit of the kidney (~ 1 million in the kidney)
-->Amt. of nephrons DECREASE as you age

Albuminuria

-->One of the first signs of diabetic neuropathy, due to plasma protein being filtered into the blood

Diabetic nephropathy

-->a microvascular complication associated with damage to the small blood vessels that supply the glomeruli of the kidney
-->kidney's filtration mechanism is stressed, holes and fibrous tissue develop
-->End resut protein leaks out into urine("proteinuria")

Signs & Symptoms of Renal Disorders

Anemia
Haematuria (red cells in urine)
Proteinuria (protein in urine)
Polyuria (large volume of urine)
Oliguria (small volume of urine)
Anuria (less than 50ml/day)
Anasarca (generalized edema)
Hypertension
Vitamin D deficiency
Uremia (accumulation of nitrogenous wastes)

Anemia

--> A decrease in the number of RBCs or less than the normal quantity of hemoglobin in the blood

Haematuria

-->RBC's in the urine

Proteinuria

-->Protein in the urine

Oliguria

-->Small volume of urine (*** < .5L of urine)

Anuria

-->Nonpassage of urine (*** < 50ml / day)

Anasarca

-->A form of non-localized GENERALIZED EDEMA (a decr. in the oncotic pressure in urea

Hypertension

-->An increase of hypertension (Glomerulonephrities or Nephrotic Conditions)

Vitamin D Deficiency

-->Due to lack of production of the **active form of vitamin D**

Uremia (or "End Stage Renal Disease")

-->Accumulation of NITROGENOUS WASTES WITH clincal symptoms
-->Leads to very severe RENAL FAILURE where there is a need for DIALYSIS
-->More severe than AZOTEMIA

Azotemia

-->A ccumulation of NITROGENOUS WASTES OR AZOLEWITHOUT clinical symptoms

Polyuria

-->Excessive production of urine > 3L over 24 hours
(***.5 - 1.5L of urine is normal)

Functional Anatomy of the Kidney

-->The RENAL ARTERY enters, & the RENAL VEIN & URETER leave at the HILUS
-->The medulla composed of 10-18 pyramids, is surrounded by the CORTEX (houses the renal corpuscles, the distal & proximal convoluted tubules, and the medullary rays)
-->Renal ("Medullary") Pyramids
1)Moves from apex toward the medial surface
2)Papillary duct ("Renal papilla")in the renal pyramid drains into the minor calyx
-->Major Calyces (3,4 in kidney)
1)Forms the RENAL PELVIS (Upper part of the ureter)
-->Renal Column ("Column of Bertin")
1)Btwn. Pyramids; Part of the cortical tissue
-->Medullary Rays
1)Continuation of medullary tissue from base of the pyramid that extends into cortex
2)Contains straight tubules & collecting tubles

Features of Sections of the kidney

(1) Renal Cortex
-->***Contains mainly GLOMERULI & TUBULES
(2)Renal Medulla
-->**Mainly contains LONG LOOPS OF HENLE, TERMINAL REGIONS OF COLLECTING DUCTS & VASA RECTA

Parts of the Nephron (Functional Unit of the Kidney)

1)Renal Corpuscle
-->Region where filtration of plasma occurs
2)Renal Tubule
-->Region of ***reabsorption (tubular fluid --> blood) & secretion (blood --> tubular fluid)

Functional components of the nephron

1)Glomerulus (Contains Bowman's capsule, glomerular capillary network, afferent & efferent arterioles
2)Proximal Convoluted Tubules
3)Loops of Henels (Contains Ascending & Descending Loops)
4)Distal Convoluted Tubule
5)Collecting Duct

Pathway of Urine Drainage

Urine-->Collecting Duct-->Papillary Duct-->Minor Calyx-->Major Calyx-->Renal Pelves-->Ureter-->Urinary Bladder

Renal Papilla

-->Is the APEX of the renal pyramid

Major Segments of the Kidney Tubules

(1)Proximal Tubule
-->Contains the Convoluted & Straight Part ("Pars Recta")
(2)Loop of Henle (3 Major Parts)
-->Thin Descending Limb (From the end of the proximal tubules to the tip of the loop of Henle)
-->Thin Ascending Limb (From the tip of the Loop of Henle to the the thick ascending limb)
-->Thick Ascending Limb (From the end of the thin ascending limb to the distal convoluted tubule)
(3)Distal Convoluted Tuble (2 Main Parts)
-->Early Distal Convoluted Tubule (Touches the glomerular capillary; contains Maucla Densa Cells)
-->Late Distal Convoluted Tubule (Does not touch the glomerular capillar; does not contain macula densa cells)
(4)Connecting Tubule (Drains into the collecting duct)
(5)Collecting Duct (Determines the final concentration of urine that will eventually drain into the renal pelvis via the **renal papilla**; takes urine out of the kidney)
--->Contains 3 parts (Cortical, Outer Medullary, & Inner Medullary Collecting Duct)
-->Highly permeable to H2O due to **ADH**

Increase Osmolarity in the Medullary Interstitium

-->Has to be RAISED in order to reabsorb H2O from the renal tubules into the INTERSTITIAL FLUID

Requirements in order to increase excretion

1)Increase the filtration rate
2)Increase the secretion into the renal tubules

Epithelial cells that line the tubules

-->Make the descending & ascending limb

Peritubular Capillaries

-->Arteries that surround the tubules
-->***Helps secrete & reabsob solutes into the proximal & distal convoluted tubules
-->Provides the blood supply to respective part of kidney (via the "Vasa Recta" system that branches off of it)
-->Helps maintain the osmotic gradient in medullary interstitium

Total Renal Blood Flow & Amount of cardiac output (CO) that flows through the kidney

-->~25% of cardiac output flows through the kidney (1.2 L/min or 1200 ml/min)
-->Of that 1200 mil, 600 ml/min flows through the blood plasma

Pathway of Blood Supply of the Kidney

Renal Artery -->Intersegmental Artery-->Interlobar Arteries-->Arcuate Arteries-->Interlobular Arteries-->Afferent Arterioles-->Glomerular Capillaries-->Efferent Arterioles-->Peritubular Capillaries/Vasa Recta-->Interlobular Veins-->Arcuated Veins-->Interlobar Veins-->Intersegmental Veins-->Renal Veins (Takes blood to IVC)
--
-->NOTE: Keep in mind that their are 2 kidneys in the human body (so values may need to multiplied by 2)

2 Major Types of Nephrons

1)Cortical Nephrons
-->Represent MAJORITY of all nephrons (7/8ths)
-->Glomeruli/Renal Corpuscle located in OUTER CORTEX
-->Contains SHORT LOOPS OF HENLE that descend from the CORTEX-->OUTER MEDULLA
-->Tubules are supplied by the PERITUBULAR CAPPILLARIES (**Do not contain vasa recta**)
-->Peritubular Capillaries are essential for tubular transport (reabsorption/secretion)

2)Juxtamedullary Nephrons
-->Represent MINORITY of all nephrons (1/8th)
-->Glomeruli/Renal Corpuscle located in the COTICOMEDULLARY JUNCTION
-->Contains LONG LOOPS OF HENLE that descend from the OUTER-->INNER MEDULLA
-->Tubules are supplied by the VASA RECTA & PERITUBULAR CAPPILARIES
[Vasa recta are parallel to the loop of henle; contain a "hairpin turn"]
-->Vasa Recta serves a ***countercurrent exchanger that is essential for the production of concentrated urine

Blood Circulation of the Kidney

1)Renal Artery: Brings blood supply to the kidney; divides into the smaller; Divides into small branches that end as afferent arterioles
2)Afferent Arterioles: Branch out into glomerular capillaries
3)Glomerular Capillaries: Send blood to efferent arterioles
4)Efferent Arterioles: Send blood supply into the peritubular capillaries
5)Peritubular Capillaries: Eventually drains into renal vein
***Major Diff. betwn systemic & renal blood circulation is the presence of 2 capillary beds instead of one

Macula Densa Cells

-->Specialized portion of the early distal tubule facing the VASCULAR POLE of the renal corpuscle
-->Monitors the osmolarity, volume, and NaCl content of the liquid as fluid flows from the thick ascending limb to the DCT
1)Will send signals to the juxtaloglmerular cells based on the NaCl- concentration in the fluid

Juxtaglomerular Cells

-->Modified smooth muscle located in the wall of the **afferent arteriole**
-->Senses signal of changes in blood pressure from macula densa, and produces RENIN
-->Contains β1 Receptors for release of renin

Components of Renal Corpuscle

-->Contains 2 major structures (Glomerular capillaries & Bowman's Capsule)
-->Glomerular Capillaries (Interconnected capillary loops)
-->Bowman's Capsule (Surrounds capillary tuft)
1)Plasma is filtered into the bowman's space
2)Opens into the proximal convoluted tubule
-->Contains 2 major layers (Parietal & Visceral Layer)
1)The parietal layer is the OUTER layer of the capsule
2)The visceral layer is the INNER layer that covers the glomerular capillaries

Bowman's Capsule

-->Contains VISCERAL & PARIETAL LAYER
1)Visceral Layer: Covers the glomerulus
2)Parietal Layer: Outer layer of the renal corpusule
-->Has 2 Poles (VASCULAR & URINARY POLE)
1)Vascular Pole contains the afferent & efferent arteriole
2)Urinary Pole where ultrafiltrate enters from the visceral layer of the Bowman's Capsule
-->Bowman's Space: Is the site of urine formation after passing through the FILTRATION BARRIER

Podocytes

-->Are Cells of the ***visceral layer of the Bowman's Capsule
(Parietal layer of Bowman's Capsule contains Simple Squamous Epithelium)
-->Contains 2 types of processes:
1)Primary Process (Large; *Don't contact the surface of the body of the podocyte
2)Secondary Process ("Pedicles or finger-like projections"; have DIRECT contact with the surface of glomerulus; interdigitate with adj. pedicles of ANOTHER podcyte to form a *FILTRATION SLIT*)

3 Layers of Filtration Barrier

1) Endothelia; Layer(Fenestrae without diaphrams
2)Fused Basement Membrane(Basal Lamina of the Podocytes fuse with the basal lamina of the capillary vessel)
3)Podocytes ("The filtration slit")
-->The barrier is relatively UNSELECTIVE (lets molecules ~70kD or above through filtration slit
1)Important to ensure that REABSORPTION occurs to recover useful substances in the filtrate

Juxtaglomerular Apparatus

-->Located at the vascular pole of the renal corpuscule
-->Composed of 3 major parts:
1)Juxtaglomerular Cells
2)Macula Densa
3)Extraglomerular Mesangial Cells (or Lacis Cells)
-->All 3components regulate the RENAL BLOOD FLOW or GLOMERULAR FILTRATION RATE ("GFR")
--
NOTE: Juxtaglomerular cells are also known as ***Baroreceptors

Mesangial Cells

->Replace normal CT Cells; Interspered among the capillary loops of the GLOMERULUS
-->Contains 2 Major Types:
1)Intraglomerular Mesangial Cells (In Glomerulus)
2)Extraglomerular Mesangial Cells (Outside of Glomerulus; Contain Lacis Cells in the vascular pole that produce erythropoietin[EPO] )
-->Major Fxn of mesangial cells is to help in the contraction & relaxation of the glomerular cappilary
-->Contain receptors to *ANGIOTENSIN II & ATRIAL NATRIURETIC FACTOR*

Intraglomerular Mesangial Cells

-->Functions are "Contractile/Support & Phagocytic"
1)Modify the diameter of the glomerular capillaries to regulate the glomerular filtration rate (GFR)
2)Phagocytosis by acting as MACROPHAGE

2 Molecules that cannot be filtered from the plasma into the interstitial fluid under NORMAL circumstances

1)Plasma Proteins
2)RBC's

Hydrostatic Pressure of the glomerular capillaries vs. other areas of the body

1)Hydrostatic pressue in the glomerular cappillaries (45-60 mm Hg)
2)In other tissues (30 mm Hg in other areas of the body)
(***Explains why the glomerular filtration rates are much HIGHER than the filtration rates across NON-RENAL CAPILLARIES

Variables that affect the permeability characteristics of the filtration barrier

1)Permeability
2)Surface Area

Important features of the Glomerulus

-->Creates the ultrafiltrate of the blood, which is CELL FREE & PROTEIN FREE
-->Since the concentration of small solutes in the filtrate is the SAME as what is in plasma (known as the FREELY FILTRATED)
-->Glomerulus receives high blood flow

Lists of materials that are Filtered vs. Not Filtered

-->See powerpt.
--
NOTE: All H2O-Soluble forms in the plasma are FREELY FILTERABLE

Major Examples of 3 Freely Filterable Substances that are Handled Diffferently by the nephron

1)Inulin: 100% Filtered & %100% Excreted
2)Glucose: 100% Filtered & %100% Reabsorped
3)PAH (Para-Aminohippuric Acid): 100% Filtered & 100% Secreted

Features of Glomerular Filtration

-->Measured by the Glomerular Filtration Rate (GFR)

Glomerular Filtration Rate (GFR)(mL/min OR L/day)

-->Defined as the rate at which plasma is filtered into the BOWMAN's CAPSULE S of ALL functioning nephrons of BOTH THE KIDNEYS
-->Approx. 125mL/min or 180 L/day of plasma is filtered in an adult

Ultrafiltrate

-->The filtrate; Has all the components of plasma EXCEPT PLASMA PROTEINS

Basement Membrane of Filtration Membrane

-->Contain Type 4 Collagen

Additional features of the Glomerular Filtration Barrier

-->3 Layers (Endothelial Layer, Basement Membrane, & Podocytes [epithelial cells] surrounding the glomerular capillary)
-->The basement membrane is the layer that contains the MOST NEGATIVE CHARGE, but all 3 layers have some negative charge
-->PLASMA PROTEINS ARE NOT FILTERED b/c they are repelled by negative charge (if their is a loss of negative charge, albumin will be seen (filtered across the glomerular wall)

Components of Glomerular Basement Membrane)

1)Collagen
2)Laminin
3)Other extracellular matrix proteins (Ex. HEPARIN SULFATTE --> The proteoglycan that contributes the most to negative charge in the basement membrane)

Filtration Slits

-->Have SELECTIVE PERMEABILITY

Major advantages of having a selective permeability of the filtration barrier

1)Prevents the loss of plasma proteins
2)Allows large quantity of fluid to get filtered into the Bowman's Space

Importance of **Minimal Change Disease***

-->Is a disease that causes the LOSS of negative charges surrounding the basement membrane
-->Results in the LEAKAGE of proteins into the filtrate, which results in:
1)PROTEINURIA
2)EDEMA
***Mostly seen in CHILDREN

Features of Starlings Forces across the glomerular cappillaries

-->Represent the pressures that drive fluid movement across the glomerular capillary wall
-->The oncotic pressure of the Bowman's Space (~interstitial fluid) is assumed to be ZERO b/c proteins are usually NOT filtered into the interstitial fluid
***See Formula Sheet for Starlings Equation
-->In the glomerular capillaries there is only FILTRATION & NO ABSORPTION of fluid back into capillaries
-->Filtration STOPS somewhere at the end of glomerular capillaries b/c of FILTRATION EQUILIBRIUM (point where net force is equal to ZERO)
-->GFR (Glomerular Filtration Rate) referes to the reate at which the fluid is filtred into the Bowman's Space

Features of Filtration Coefficient [ K(f) ]

-->Depends on 2 factors:
1)Water permeability
2)Total Surface Area of the glomerular capillaries
--
-->K(f) of the glomerular capillaries is GREATER than the systemic capillaries due to the INCREASE OF THE TOTAL SURFACE AREA (GFR --> 180L/day)
-->Contraction of mesangial contract (decrease the surface area for filtration; Decrease in K(f) )
-->Relaxation of mesangial cells (Increases the surface areas for filtration; Increase in K(f) )

Glomerular Capillary Hydrostatic Pressure (P(gc))

-->***Main factor that determines GFR
-->Is high (45-60 mm Hg) relative to the systemic capillaries
-->***Remains constant along the entire length of glomerular capillary, BUT shows a PRESSURE DROP in the systemic capillaries
-->Decreases with a ↓MAP (↓MAP-->↓RBF (renal blood flow)-->↓Pgc-->↓GFR)

Urinary Tract Obstruction (Obstructive Uropathy)

-->Occurs when the kidney stone blocks tubular flow down the nephron
-->Leads to a ↓GFR due to a ↓P(bs)

Features of Hydrostatic Pressure in the Bowman's Space (P [bs])

-->Represents the fluid pressure in the Bowman's capsular space
-->Represent the pressure that OPPOSES FILTRATION
-->Major Examples of Postrenal Causes of Obstruction:
1)Uretic Obstruction (By a stone OR tumors of the pelvis)
2)Both examples lead to a ↓GFR, which leads to RENAL FAILURE
--
NOTE: Benign Prostatic Hyperplasia is common in MEN; Tumors of the pelvis are more common in WOMEN)
-->Is about **10 mm Hg**

Glomerular Capillary Oncotic Pressure

-->Is determined by the PLASMA PROTEIN concentration of the glomerular capillary blood
-->Represents a force that OPPOSES FILTRATION
-->It progressively INCREASES as blood flows in the glomerular capillary due to a higher rate o filtration at the arteriorlar end vs the venous (efferent) in

Oncotic Pressure of the fluid in the Bowmans Space

-->Represents the force created by the proteins that are present in the BOWMAN'S SPACE
-->Should be negligable b/c proteins are normally are NOT FILTERED into the caspular space)

Major Differences btwn the begininning & the end of the capillary

1)At the beginning of the capilllary
-->The net filtration of plasma occurs due to the OUTDRIVING FORCE all along the glomerular capillary
2)At the end of the capillaryy
-->The net filtration of stops at the EFFERENT END OF THE GLOMERULAR CAPILLARY due the**filtration equilibrium**(the point where the increase in oncotic pressure in the GC completely opposses hydrostatic pressure in GC)

Regulation of GFR

-->is AUTOREGULATED (i.e. kept constant) over a range of 80-180 mm Hg (wide range)
-->Renal blood flow (RBF) DIRECTLY influences GFR, INDEPENDENT O THE STARLING FORCES (↑ the RBF, ↑ in GFR)

Equation of GFR that relates GFR to filtration coefficient (K[f]) & Pressure (P[f])

-->Increase in K[f] leads to ↑GFR occurs when:
1)Increase in the blood flow to the kidney (↑Q)
2)Agents that relax mesangial cells --> Increase surface area for filtration (Ex. ***ANP & Dopamine)
3)Inflammation (↑ permeability of the filtration barrier
-->Decrease in K[f] leads to a ↓GFR occurs when
1)↓ in functioning glomeruli --> ↓ in surface area filtration --> ↓GFR
2)Agents that contract mesangial cells (***Angiotensin II, Norepinephrine, Arginine Vassopressin OR ADH)--> ↓ in surface area filtration --> ↓GFR
3)Thickening of filtration barrier (***Seen in diabetes mellitus) --> ↓ in surface area filtration --> ↓GFR

Agents that relax mesangial cells

1)ANP
2)Dopamine

ANP

-->A molecule that is secreted by the CARDIAC CELLS when there is an ↑in strech of the heart muscle (i.e. ↑blood volume)
-->Acts on the kidneys to INCREASE Na+ excretion, which lowers blood pressure OR blood volume by:
1)Dialating afferent arterioles & relaxing mesangial cells (Incr. glomerular filtration)
2)Inhibits Na+ reabsorption at the renal tubules

Agents that contract mesangial cells

1)Angiotensin (Powerful vasocontrictor)
2)Norepinephrine (NE)
3)Arginine Vassopressin (AVP) or ADH

Consequences of ↑ in P[bc]

**Leads to a DECREASE in GFR**
-->Major Examples:
1)Renal Stones
2)Ureteric Obstruction OR Constriction of the Ureter (***Examples of POSTRENAL FAILURE)
3)Complication of Abdominal Surgery
-->Mechanism:
1) Obstruction to urine flow --> ↑ in P[bc] --> ↓ in NFP (net filtration pressure) --> ↓ in GFR

Effects of independent isolated constrictions OR dialations of afferent & efferent arterioles

P[gc] vs. P[ptc]

-->P[gc] = 45-60 mm Hg
-->P[ptc] = 7-8 mm Hg

Special Features of Renal Vasculature

-->Contains 2 sets of ARTERIOLES & 2 Sets of CAPILLARY BEDS in ***Series
-->Glomerular capillary bed has a HIGH PRESSURE (due to prescence of an additional resistance ahead of it) necessary for **FILTRATION**
-->Peritubular capillary bed has a LOW PRESURE (due to the prescens of an additional resistance BEHIND IT) necessary for reabsorption

Clincal featrues of DEHYRATION

-->Due a a LOSS of blood volume, you must *CONSTRICT THE EFFERENT ARTERIOLES** in order to INCREASE REABSORPTION of solutes
-->Mechanism:
1) ↓BV --> ↓RBF --> ↑Renin --> ↑Angiotensin II --> Leads to efferent arteriolar constriction --> Upstream affects (↑P[gc], ↑GRF, ↑RBF) --> Downstream affectis (↓P[ptc] --> *** INCREASES reabsorption of the blood)

Angiotensin II

-->The molecule that is mainly responsible for ***constricting the efferent arterioles (↓P[ptc], leading to ↑ in reabsorption)
-->Also ↑P[gc] --> ↑GFR
-->**IMPORTANT**: is the main molecule responsible for maintaing GFR in patients with renal stenosis

Renal Artery Stenosis & relationship to AG II

-->Causes a decrease in RBF --> ↓P[gc] & ↓in GFR
-->However, RAA system still works, which produces Angiotensin II, the main molecule responsible for maintaining GFR in patient with RENAL STENOSIS
1)↑Renin, ↑AG II
2)Patients also present with hypertension b/c of ↑BV due to the RAA
-->Patients with renal artery stenosis must NOT lose activity of AG II [Ex. ***ACE Inhibitors]
1)ACE Inhibitors are contraindicated in patients with renal artery stenosis
2)You're not supposed to give ACE inhibitors if you suspect secondary hypertension due to renal artery stenosis

Major Difference in Renal Blood Flow (RBF) vs Renal Plasma Flow (RPF)

-->Renal Blood Flow (RBF)
1)Measures how much blood gets into your kidneys
-->Renal Plasma Flow (RPF)
1)Measures how much plasma gets into your kidneys
***Out of 100 ml of blood, 55 ml is your packed blood cells (55ml), & 45 ml remaining in the plasma

Features of Renal Blood Flow (RBF)

-->Receives ***25% of cardiac output (1200 m;/min)
-->Flow is non-uniform in the CORTEX vs. MEDULLA
1)↑Q to cortex for ↑ amtsl of filtration at the glomeruli
2)↓Q to medulla to keep the HIGH OSMOLARITY of the medullary interstitium
-->RBF is **AUTOREULATED**
-->Measured by **Fick Principle* using *PAH**(para-amino hippuric acid; meaures renal blood flow in the kidney )

Regulation of Renal Blood Flow (Q)

-->See Formula Sheet for details

Regulation of Renal Blood Flow (RBF)

1)Sympathetic NS & Circulating Catecholamines
2)Angiotensin II
3)Prostaglandins (***Locally Produced)
4)Dopamine

Features of Sympathetic NS & Circulating Catecholamines

-->Both afferent & efferent arterioles are innvervated by **vasoconstriction* by activating *α1-receptors**
1)There were far more α1 receptors on AFFERENT ARTERIOLES than efferent arterioles
2)Afferent arterioles therefore have an increased response to Epinephrine
-->Mechanism:
1) Constriction of afferent arterioles --> ↓ RBF --> ↓P[gc] --> ↓GFR
--
NOTE: There is a larger DECREASE in renal plasma flow compared to GFR if ther is ***constriction of the afferent arteriole due to sympathetic stimulation

Important point of sympathetic stimulation

-->Sympathetic stimulation has NO INFLUENCE to renal blood flow under normal conditions
-->***Only with a ↓↓↓MAP will cause SYMPATHETIC STIMULATION
1)Under this scenario, sympathetic stimulation constricts blood flow even in conditions when theri is a ↓↓↓ in MAP to ↑ PREFUSION to critical areas such as the BRAIN

Angiotensin II

-->Is a potent vasoconstrictor of BOTH the afferent & efferent arterioles
-->However, the EFFERENT ARTERIOLES are MORE sensitive to the AG II effects
-->In the presence of LOW LEVELS of AG II, the EFFERENT ARTERIOLES are peferentially CONSTRICTED, leading to a INCREASE IN GFR
-->In the prescence of HIGH LEVELS OF AG II. BOTH AFFERENT & EFFERENT ARTERIOLES are consticted, leading to a DECREASE IN GFR

Prostaglandins

-->Increase in RBF by VASODIALATION (Ex Via Prostaglandin E2 & I2)
-->***The following compounds INHIBIT prostaglandin synthesis by inhibiting the action of CYCLOXYGENASE:
1)NSAIDS
2)Acetaminophen
3)COX-2 Inhibitors
4)Aspirn

Important examples of NSAIDS to know

1)Ibuprofen
2)Naproxen
3)Dicloferac
--
-->Patients that used NSAIDS on a continual basis can lead to a ↓ in RBF (***Must be monitored for RENAL FAILURE due to decr. in RBF)
-->NSAIDS are used to inhibit COX enzyme to stop the production of prostaglandins

Prostagladins

-->Keep blood vessels dialated, which INCREASES flow to the nephron (↑ RBF)
-->Clinically important to use when the patient is suffering from:
1)Hypotension
2)Hyperventilation

Dopamine

-->Increase the RBF by causing VASODIALATION in the **Renal Vasculature**
-->CONSTRICTS the skeletal muscle & cutaneous arterioles
-->Used to treat HEMORRHAGIC SHOCK

Molecule used to treat Hemorrhagic Shock

***Dopamine

Features of Autoregulation of Renal Blood Flow

-->Kept constant over a wide range of MAPs (***80-200 mm Hg)
-->Renal vascular reistance (RVR) changes proportionately as the MAP changes (Q = ∆P/R)
-->***Afferent arteriole is the major site of RESISTANCE
-->There are 2 major hypotheses for why renal autoregulation occurs:
1)Myogenic Hypothesis
2)Tubularglomerular Feebackback Mechanism

Myogenic Hypothesis

-->Involves reflexive vasoconstriction or vasodialation to help keep MAP at a constant value
-->In response to a ↑ in MAP (or ↑ Renal arterial pressure (RAP ):
1)↑MAP --> ↑stretch --> Opening of stretch-activated Ca2+ channels (in smooth muscle membrane) --> Reflexive coontraction (in smooth muscles of afferent arterioles) --> ↑arteriolar resistance to renal blood flow (*Visa Versa for the other scenario)

Tubularglomerular Feedback Mechanism

-->Regulates the glomerular hydrostateic pressure (P[gc]) to increase or decrease the GFR in response to the arterial pressure [keeps MAP/RAP Constant]
-->Mechanism when you have a ↑MAP/RAP leading to a ↓in GFR
1)↑MAP/RAP --> ↑RBF --> ↑P(gc) --> ↑GFR --> ↑ delivery of NaCl to juxtaglomerular apppartus --> ↑Macula Densa Cell Secretion of ADENOSINE/KININS --> ↑Afferent arteriolar constriction --> ↓RBF, then ↓GFR --> ↓ in MAP/RAP

Major Characterisitcs of a Renal Plasma Marker (***See slide #54 for picture)

1)Must be freely filterable across the glomerular capillaries
2)Must be cleared (removed) by the kidney COMPLETELY(**So Renal Plasma Flow measures the *CLEARANCE** of a substance)
--
-->No substance exactly meets this criteria, but the closest to it is **PAH**
1) 20% of the PAH entering the RA is filtered
2)80% of the remainng PAH in the arterial blood flows through the peritubular cappillaries to be SECRETED back into the tubular fluid **theoretically**(which can be used to generate ACTUAL RENAL PLASMA FLOW)
3)***In reality, the secretion is INCOMPLETE b/c the blood in the renal capsule & adipose tissue cannot be measured (i.e. < 80% is secreted back into the renal tubules; some of the PAH will not be secreted & will return to the circulation --> KNOWN AS THE EFFECTIVE RENAL PLASMA FLOW)

Features of the Fick Principle

-->States that amount of the substance entering the kidney (Renal Artery) is EQUAL to the amount of the substance leaving the kidney (Renal vein) AND the amount excreted into the urine
-->***See formula sheet
-->The molecule commonly used is **PAH**
-->The Fick principle is used to measure the **EFFECTIVE RENAL PLASMA FLOW**, so according to the Fick Principle:
1)Almost 100% of all PAH entering the kidney is excreted into the urine
2)The Renal Vein concentration of PAH is nearly ZERO
--
NOTE: PAH concentration in renal artery is EQUAL to the PAH concentration in **ANY PERIPHERAL VEIN**

Amount of Plasma In the Kidney that is CLEAR of PAH ("Effectively")

-->The clearance of PAH is EQUAL to effective renal plasam flow (RPF)
1) Effective RPF = **600 ml/min**

Filtration Fractrion (FF)

-->Represents the fraction of the **RPF** that was filtered across the glomerular capillary
-->Can be expressed as a formula relating GFR to RPF (**See Formula Sheet**)
1)Normal rate of GFR is ~125 ml/min
2)Normal Rate of RPF is 600 ml/min
-->A normal filtration fraction is .15 to .20 (15-20%)
1)Which indicates that ~15-20% of the RPF is FILTERED & 80% of the RPF is NOT FILTERED
-->Other important points:
1)The FF of proteins should be 0% b/c normally the kidneys DO NOT FILTER THE<
2)A poorly filtered substance will have a FF of less than 15%

Changes to FF when the total renal blood flow (RBF) is LOW

-->When the RBF is LOW (↓RPF), the FF increases if GFR is constant in MOST CASES b/c:
1)↓ ↓Plasma flow through the glomerulus
2)↑ tendency of the plasmato filter out of the real capillary & into the Bowman's Space
3)↑ FF (will increase in most, but not ALL cases)

Factors that affect the filtration fraction (FF)

1)Renal Plasma Flow (RPF)
2)Efferent Arteriolar Constriction
3)Sympathetic Stimulation
4)Constriction/Obstruction of the Ureter

Renal Plasma Flow (RPF) & FF

-->As you ↓ the RPF (i.e. increased time fluid remains in glomerular capillaries), the FF has a **tendency to increase** (does not occur in all stituations; SEE SYMPATHETIC STIMULATION)

Efferent arteriolar constriction & FF

-->***↓ RPF & ↑GFR, which leads to an INCREASE in FF b/c:
1)The DECREASE in RPF is not as LARGE as the increase in GFR (higher) so therir is a ↑ in FF

Sympathetic Stimulation & FF (***Special Case)

-->Their is a INCREASE in FF by vasoconstriction despite the vasoconstriction of via the sympathetic stimulation
-->Their is a LARGER decrease in RPF than a decrease in GFR leads to an increase in FF b/c:
1)The strength of vasocontriction is greater on the AFFERENT ARTERIOLES (↓RPF & ↓GFR) than the EFFERENT ARTERIOLES (↓RPF & ↑GFR)

Constriction / Obstruction of the ureter (*Or Uretral Stone*)

-->Urine cannot flow through the ureter to bladder (causing urine to back up to the kidney)
-->As a reuslt the HYDROSTATIC PRESSURE in the nephrons will increase as far back as the BOWMANS SPACE
-->Producing an INCRASE in P[bs]
-->An increase in P[bs] --> ↓GFR, which leads to a ↓FF

Effect of the changes in Starling Forces on RPF, GFR, and the Filtration Fraction (FF)

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