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COUNTER CURRENT MECHANISM (CONCENTRATION MECHANISM OF URINE)

Lecture – 7

Dr. Zahoor

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COUNTER CURRENT MECHANISM Kidney can excrete dilute or

concentrated urine depending on body state of hydration

Body fluids are isotonic having osmolarity of 300 milliosmoles/liter (mOsm/l)

Depending on body state of hydration kidney can excrete urine having osmolarity from 100 – 1200 mOsm ( Normal urine Osmolarity is about 500 – 600 mOsm )

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COUNTER CURRENT MECHANISM Concentration of urine is the function of

juxta -medullary nephron, which has long loop of Henle which goes down deep in the medulla

Also, the vasarecta (capillaries) of juxta medullary nephron follow the same deep loop of Henle

Flow in the both long LH and vasarecta is considered counter current because flow in two limbs of the loop move in the opposite direction

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Juxta medullary and cortical nephron

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COUNTER CURRENT MECHANISM Concentration of urine is due to 1. Juxta medullary nephron – long loop of Henle

establish (create) the vertical osmotic gradient 2. Vasarecta help to maintain (preserve) this

osmotic gradient 3. Collecting duct of all nephrons use the

gradient along with hormone vasopressin (ADH) to produce urine of varying concentration

4. Urea also help in urine concentration mechanism

This entire functional organization is known as medullary counter current system

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COUNTER CURRENT MECHANISM We will discuss in detail each point 1- Medullary vertical osmotic

gradient - created by loop of Henle is called Counter current multiplier

- Long loop of Henle in juxta medullary nephron establishes the vertical osmotic gradient. How?

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COUNTER CURRENT MECHANISM As filtrate is formed, it is isotonic in the

PCT, water is reabsorbed in PCT, secondary to Na+ active reabsorption

When isotonic fluid enters the loop of Henle changes occur in the descending and ascending limbs of long henles loop

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PROPERTIES OF DESCENDING AND ASCENDING LIMBS OF LH Descending limb of long LH is highly

permeable to water due to AQP – 1 water channel which are always open

Descending limb is not permeable to Na+, therefore, Na+ remains in the descending limb of LH and its concentration (osmolarity) increases

Maximum osmolarity is at the tip of LH which is 1200 mOsm/l

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PROPERTIES OF DESCENDING AND ASCENDING LIMBS OF LH Ascending limb of LH actively transports

NaCl out of tubular lumen into interstial fluid

Ascending limb is impermeable to H2O As NaCl leaves and H2O remains,

osmolarity decreases in the ascending limb of loop of Henle

Fluid entering the DCT has low osmolarity of 100 mOsm/l

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Osmolarity of

fluid in different segment

s of tubule

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PROPERTIES OF DESCENDING AND ASCENDING LIMBS OF LHIMPORTANT As Na+ is actively transported out of

ascending limb of LH, concentration increases in the interstitial fluid surrounding the loop of Henle

This increased concentration in the interstitial fluid achieved by loop of Henle is known as Counter Current Multiplication

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COUNTERCURRENT MULTIPLICATION

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VERTICAL OSMOTIC GRADIENT IN THE RENAL MEDULLA

A large, vertical osmotic gradient is established in the interstitial fluid of the medulla

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BENEFITS OF COUNTER CURRENT MULTIPLICATION What is the benefit of fluid getting

concentrated in the descending limb of LH and again diluted in the ascending limb of LH?

Benefits are - It establishes a vertical osmotic

gradient in the medullary interstial fluid - This gradient is used by collecting ducts

to concentrate the tubular fluid (urine)

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BENEFITS OF COUNTER CURRENT MULTIPLICATION As fluid is hypotonic as it enters CT, the

kidney can excrete dilute urine or it can be concentrated in the CT. How ?

- ADH controls water reabsorption in DCT and CT. About 20% of H2O enters DCT and CT, and it is under control of ADH

NOTE - We know that in PCT 65% of water is reabsorbed and in LH 15% of water is reabsorbed

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2. ROLE OF VASOPRESSIN (ADH) As fluid enters the CT, it is hypotonic. For water reabsorption to occur in CT,

Two criteria must be met: 1. Osmotic Gradient across the CT – it is

there as interstial fluid is concentrated by LH- counter current multiplication

2. Collecting tubule must be permeable to water, it is there due to presence of ADH (normally DCT and CT are impermeable to H2O)

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ROLE OF VASOPRESSIN (ADH) How ADH increases the permeability of

DCT and CT? - ADH binds to V2 receptors, which are G-

protein receptors which activate cAMP, second messenger in DCT and CT

- It increases the permeability to water by insertion of Aquaporins (AQP-2 water channels in the luminal membrane)

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Mechanism of action of ADH

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3. VASARECTA – COUNTER CURRENT EXCHANGER We will study vasarecta, which works as

counter current exchanger and preserves the medullary osmotic gradient, created by LH

Vasarecta are freely permeable to NaCl and H2O. As blood passes down the descending limb of vasarecta, it picks up salt and loses H2O, till it is hypertonic at the bottom(1200 mOsm ).

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VASARECTA – COUNTER CURRENT EXCHANGER As blood flows up in the ascending limb

of vasarecta, salt moves into the interstium and water enters the vasarecta, therefore, concentration falls in the ascending limb of vasarecta ( 300-350 mOsm ).

This passive exchange of NaCl and H2O in the descending and ascending limbs of vasarecta and interstial fluid is known as counter current exchange

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VASARECTA – COUNTER CURRENT EXCHANGE IN THE RENAL MEDULLA

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• The vasa recta serve as countercurrent exchangers

THE VASARECTA PRESERVE HYPEROSMOLARITY OF RENAL MEDULLA

• Vasa recta blood flow is low (only 1-2 % of total renal blood flow)

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IMPORTANT Loop of Henle – counter current

multiplier establishes the concentration gradient in the medullary interstitial fluid.

Vasarecta – counter current exchanger maintains the concentration gradient in the medullary interstitial fluid.

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4. ROLE OF UREA IN CONCENTRATION OF URINE Urea contributes to hyper osmotic renal

medullary interstial fluid and to concentrated urine. How ?

- Urea is absorbed in PCT – 50% - 50% urea comes to DCT and CT, they

are not permeable to urea but collecting duct in the inner medulla is permeable

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ROLE OF UREA IN CONCENTRATION OF URINE- UREA CYCLE

- When water is reabsorbed in DCT and CT under action of ADH, urea is more concentrated

- Urea diffuses from CT in the inner medullary region and contributes to the concentration of medullary interstial fluid

- Increased urea present in the interstial fluid diffuses into loop of Henle (descending and ascending limbs) and then to DCT and CT, therefore, recirculates many times before it is excreted – called Urea Cycle

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Figure 28-5; Guyton and Hall

Recirculation of Urea Absorbed from Medullary

Collecting Duct into Interstitial Fluid

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REGULATION OF WATER REABSORPTION IN RESPONSE TO H2O DEFICIT

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REGULATION OF WATER REABSORPTION IN RESPONSE TO H2O EXCESS

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MICTURITION REFLEX Micturition or Urination is the process by

which bladder is emptied, and is governed by two mechanism:

1. Micturition Reflex 2. Voluntary Control

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MICTURITION REFLEX

1. Micturition Reflex It is initiated when stretch receptors in

the urinary bladder are stimulated Bladder can accommodate 250 –

400ml of urine Urine urge is felt when there is

150ml of urine in the bladder

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There are 3 phases of vesicular pressure changes1. Initial 10 cm of H2O rise in

pressure for 10-50 ml of urine collection

2. Second phase last until the bladder volume is 400ml

3. Third phase shows the sharp rise in the intravesicle pressure

•Micturition contractions begin to appear at a urine volume about 150 ml.•Desire to void urine occurs when the bladder is full.

Normal Cystogram

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MICTURITION REFLEX When amount of urine increases, there is

greater distension – afferent impulses from stretch receptors go to spinal cord via pelvic nerves.

Center in the spinal cord is S2,3,4

Efferent impulses pass via parasympathetic nerves to the bladder

Parasympathetic supply causes bladder smooth muscle to contract and urine is expelled through urethra by force of bladder smooth muscle contraction

IMPORTANT – Micturition reflex is spinal reflex

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Urinary Bladder and Its Innervation

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MICTURITION REFLEX

1. Voluntary Control of Micturition Micturition is spinal reflex , but facilitated and inhibited by higher Brain centers. - Voluntary Control is done by tightening

the external uretheral sphincter and pelvic diaphragm , through pudendal nerve by impulses coming from brain, pons and cerebral cortex to the spinal cord

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Reflex and Voluntary Control of Micturition

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APPLIEDUrinary Incontinence Urinary Incontinence is loss of voluntary

control over urination, therefore, inability to prevent discharge of urine

Cause – spinal cord injury to S2,3,4

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RENAL FAILURE Renal Failure causes kidney functions to be

affected Causes of Renal Failure 1. Infections – urinary tract infection 2. Toxic agents e.g. lead, arsenic, pesticides 3. Drugs – aspirin 4. Immune response glomerulonephritis,

following post streptococcal throat infection 5. Kidney stone, tumor, enlarged prostate

gland

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RENAL FAILURE Renal failure maybe - Acute Renal Failure - Chronic Renal Failure

1. Acute Renal Failure – sudden with decreased urinary output, less than 500ml per day

2. Chronic Renal Failure – slow progressive loss of renal function. It is not reversible

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IMPORTANT Only 25% of kidney tissue is needed to

adequately maintain all the functions of kidney

When 75% of kidney tissue is destroyed then loss of kidney function is noticeable

End stage renal failure – when 90% of kidney function is lost

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CHRONIC RENAL FAILURE (CRF) Chronic renal failure can cause - Uremia (increased blood urea level) - Metabolic acidosis - Hyperkalemia - Na+ imbalance - Hypertension - Edema (loss of plasma protein) - Anemia (decreased erythropoietin)

Treatment for CRF - Dialysis - Kidney transplantation

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WHAT YOU SHOULD KNOW ABOUT THIS LECTURE Describe the factors that determine the

ability of loop of Henle to create osmotic medullary gradient

Identify countercurrent multiplier and countercurrent exchange systems in concentrating and diluting urine

Explain changes in osmolarity of tubular fluid in the various segments of the loop of Henle when concentrated urine is being produced.

Describe the role of ADH on the ability of the kidney to produce either a dilute or a concentrated urine.

Micturition reflex.

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THANK YOU