Download BY2202 The Kidney and Urinary Tract Origin, Form and Function 2

BY2202
The Kidney and Urinary Tract
Origin, Form and Function 2
Dr. Neil Docherty
Todays Objec-ves •  To link functional phenomena (filtration, reabsorption,
secretion) to functional endpoints (focus on volume
regulation)
•  With respect to blood volume and cellularity, to describe
the kidney as an effector of and responder to neurohormonal control
•  To detail the basic functional anatomy of the lower urinary
tract and explain the basis for urinary continence
The Renal Tubule Summary of Regions • 
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Proximal convoluted tubule Proximal straight tubule Thick>thin descending limb of Loop of Henle Thin>thick ascending limb of Loop of Henle Distal convoluted tubule Connec>ng tubule Collec>ng tubule Functionality Associated With Nephron
(8 KEYWORDS)
The phenomena of FILTRATION, REABSORPTION and SECRETION As tuned by INTRINSIC and EXTRINSIC control mechanisms Leads to delivery on the key func>ons of •  EXCRETION •  VOLUME REGULATION •  pH REGULATION N.B. Two types of nephrons
Cortical (more excretory)
Juxtamedullary (more involved in volume regulation)
The Nature and Selectivity of The
Glomerular Filter
A selectively permeable barrier between blood and tubule lumen is formed
It is essentially 3-layered
1) Endothelial layer 2) Basement membrane and 3) Visceral Epithelium
Selectivity based on
size (4.4nm)
charge (-ve species
repelled)
Concept Check -­‐Why filter the blood? The Glomerular Filtration Rate (GFR)
And Its Determinants
The overall GFR is the total volume of fluid filtered by the glomeruli of both kidneys per unit time
NET PRESSURE (SINGLE NEPHRON) NET RATE (GLOBAL RENAL FUNCTION) Stroke Volume (SV)=70ml Heart Rate (HR)=72bpm CO=HR*SV=5040ml/min Renal Blood Flow(RBF)=20-­‐25% of CO =Approximately 1L/min Renal Plasma Flow (RPF)=RBF*1-­‐haematocrit =1000*0.6 =600ml/min Presuming pressures detailed on the right 20% of the RPF is subject to filtra>on =600*0.2=120ml/min =180L/day =Total ECF volume of body is filtered around 10 -mes/day! Alter Arteriolar Calibre-Alter The GFR
Concept Check
What would be the effect on the
GFR of efferent arteriolar
vasoconstriction?
Filtration, Reabsorption and Secretion in
The Tubule
WASTE-Filter or secrete then excrete
(e.g creatinine)
NUTRIENT-Filter and reasorb
(e.g. glucose)
WATER/SALTS/IONS=Filter and fine
tune reclamation
or regulate secretion to
achieve osmotic/volume
and pH balance
Following Reabsorption in The Tubule
Filtrate from Bowman's capsule flows into the proximal tubule. Here all of the glucose, and amino acids, >90% of the uric acid and ~60% of salts are reabsorbed. A large volume of the water follows them by osmosis As the fluid flows into the descending segment of the loop of Henle, water con>nues to leave by osmosis 25% and reabsorp>on of salts (25%) in ascending segment In the distal tubules, more sodium is reclaimed by ac>ve transport, and s>ll more water follows by osmosis (5%). Final adjustment of water content of the urine occurs in the collec-ng tubules (10% of reabsorp>on) Concentration of The Urine
•  The kidneys filter the blood to rid it of waste and fine tune its composi>on/volume •  Urine is the effluent from this process •  Aim is maximum waste removal in minimal volume (ability to change volume depending on circulatory volume) •  180L of filtrate per day-­‐only 1% (1-­‐2L/day) excreted as urine Key Ques>on-­‐How does the kidney manage to reclaim so much of the filtrate? Concentration of The Urine Relies on The
Countercurrent Multiplier
From Two Slides Back As the fluid flows into the descending segment of the loop of Henle, water con3nues to leave by osmosis with exclusive reabsorp3on of salts in ascending segment N.B. Urinary Concentra>on basically facilitated by •  The countercurrent arrangement of the limbs of the Loop of Henle •  Differen>al permeability to water therein •  Arrangement of post-­‐glomerular capillaries in parallel Visualising The Countercurrent Multiplier
Values are mOsm (measure of osmotic strength)
Example of Nutrient Reabsorption
Glucose Reclamation in The Proximal Tubule
•  Same transport process as that seen in small intes>ne (seek lectures 18 and 19) •  Saturable Concept Check Saturability of renal glucose transport explains the term diabetes mellitus. Can you make sense of this statement? Sensing of Filtration Pressure
and Filtered Sodium Load Allow The Kidney
To Monitor and Balance ECF Volume and Tonicity
Imagine an acute decrease in blood volume
1) How will this affect CO?
2) How will this affect pressures in the renal blood vessels?
3) How will that in turn affect GFR?
4) How might the change in GFR affect sodium levels in the forming urine?
•  THE KIDNEY WILL ACT TO NORMALISE BLOOD FLOW AND ENHANCE
RECLAMATION OF SODIUM AND WATER
•  IT DOES SO BY SENSING THESE CHANGES IN SPECIALISED AREAS OF THE
RENAL BLOOD VESSELS AND TUBULE
(THE JUXTAGLOMERULAR APPARATUS-JGA)
•  A MAJOR EFFECTOR OF HOMEOSTATIC CORRECTION
IS THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS)
The Juxta-Glomerular Apparatus
Afferent arteriolar pressure Macula densa in the distal tubule (salt sensor) Sympathe>c nervous input Juxtaglomerular cells renin release In Our Example An acute decrease in circula>ng blood volume reduces CO and GFR. This reduces stretch of the afferent arteriole and also reduces delivery of sodium to the macula densa through reduc>ons in GFR. More generally the drop in blood pressure has caused a reflex ac>va>on of renal sympathe-c nerves All of these changes conspire to induce juxtaglomerular cells to release the enzyme renin Renin and Angiotensin II
Production
In Our Example •  Renin in turn causes genera>on of Angiotensin II (AngII) •  The pressor effects of AngII are mul>ple N.B. Inhibi>on of AngII produc>on or receptor engagement is the cornerstone of treatment of hypertension We will focus on one mechanism-­‐The Aldosterone Effect Aldosterone Links Renal Sodium Handling To
Blood Volume and Pressure
THE ALDOSTERONE EFFECT
In the distal tubules, sodium is reclaimed by ac>ve transport, and s>ll more water follows by osmosis (5%). Final adjustment of water content of the urine occurs in the collec-ng tubules (10% of reabsorp>on) Aldosterone enhances the above (slow steroid hormone effect) through transcrip>onal mechanisms governing sodium channel and pump expression. Target of some diure>cs (e.g. spironolactone-­‐
an aldosterone antagonist) Interes>ng Correlate-­‐Hyperaldosteronism 1)  Primary-­‐Conn’s Syndrome 2)  Secondary-­‐Renal artery stenosis In Summary
In Summary An acute decrease in circula>ng blood volume reduces CO and GFR. This reduces stretch of the afferent arteriole and also reduces delivery of sodium to the macula densa. More generally the drop in blood pressure has caused a reflex ac>va>on of renal sympathe-c nerves All of these changes conspire to induce juxtaglomerular cells to release the hormone renin which in turn causes genera>on of AngII. Among the pressor effects of AngII is induc>on of aldosterone synthesis and release from the adrenal cortex. This increase distal sodium and water reclama-on increasing volume and repressurising system On the Contrary
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Increased pressure, GFR and salt delivery to the macula
densa oppose renin release
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High venous pressure/increased venous return to
heart stretches right atrium wall
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This releases atrial natriuretic peptide which effectively
opposes everything on last slide
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Hence promoting urinary sodium loss “natriuresis” and
“depressurising” of the system
The Kidney is An Oxygen Sensor and Influences Red Blood Cell Produc-on (Erythropoesis) Renal fibroblasts and oxygen sensing Storage and Expulsion of The Urine
Blood
Tubules
Minor Calyx
Major Calyx
Renal Pelvis
Ureter
Bladder
Urethra
Substances cleared by renal excretion
The Ureters-Location
Muscular tubes taking urine from the kidneys to the bladder
30cm in length, 3mm lumen inside
Retroperitoneal (attached to posterior wall of abdomen)
Structure and Function of The Ureter
Three Layer Structure
1) Transitional epithelium
2) Longitudinal and circular
muscle
3. Adventitia (continuous
with renal capsule)
Function
Pacemaker driven peristalsis
The Uretero-Vesicular Junction
Flap Valve Design to Prevent Reflux
Urine passes out of the ureter into the bladder
Firstly though, the ureter tunnels through the bladder
wall
This causes a flap valve to be made preventing urine from
Refluxing into the ureter from bladder when full or during
pressure increase at urination
The Bladder-Location
Hollow muscular organ for temporary storage of urine
Located medially in the abdomino-pelvic cavity
The Bladder-Gross Anatomy
Ligaments attach
superior part to the
umbilicus
Ligaments attach
inferior,anterior and
posterior parts to the
Pelvic and public bone
URETHRA
The Bladder-Wall Structure
SMOOTH MUSCLE
SKELETAL MUSCLE
Coordination of voluntary and involuntary muscle contraction
required for continence and micturition
Urinary Continence
Today’s Learning Outcomes From today’s lecture you should be able to;
1) Link functional phenomena (filtration, reabsorption, secretion) to functional
endpoints (with focus on renin-angiotensinII and aldosterone dependent
mechanisms of volume regulation)
2) Briefly explain the role of the kidney as an oxygen sensor and source of
hormonal control of red blood cell production (erythropoesis)
3) Detail the basic functional anatomy of the lower urinary tract and explain the
basis for urinary continence
•  Any Ques>ons? [email protected]