LECTURE 12 (Urine concentration + dilution) Flashcards
(36 cards)
Describe how Antidiuretic hormone/Vasopressin controls urine concentration
1) When osmolarity of body fluid increases above normal (body fluid is too concentrated), posterior pituitary gland secretes more ADH
2) ADH increases permeability of DISTAL TUBULES and COLLECTING DUCTS to water
3) Allows large amounts of water to be reabsorbed and decreases urine volume, but not rate of renal excretion of solutes
OPPOSITE happens when osmolarity is reduced (too much water)
How do you dilute the filtrate as it passes along the tubule?
By reabsorbing solutes to a greater extent than water
Describe the Tubular fluid flowing through the Proximal tubule
- Solutes + water are reabsorbed in equal proportions -> little chance in osmolarity occurs -> proximal tubule fluid is isosmotic to plasma
- Tubular fluid reaches equilibrium with interstitial fluid of RENAL MEDULLA, which is HYPERTONIC -> becomes more concentrated as it flows into the inner medulla
Describe the Tubular fluid flowing through the Ascending loop of Henle
- Sodium, potassium and chloride are reabsorbed
- Impermeable to water in presence of large amounts of ADH -> tubular fluid becomes more dilute
Describe the Tubular fluid flowing through the Distal and Collecting tubules
- Sodium chloride is reabsorbed
- In absence of ADH, this portion of tubule is impermeable to water
[reabsorption of solutes + failure to reabsorb water -> dilute urine]
What does the kidney do when there is a water deficit?
Forms concentrated urine by
- continuing to excrete solutes while increasing water reabsorption
- decreasing volume of urine formed
EXPLANATION: ability of kidney to form a small volume of concentrated urine minimises the intake of fluid required to maintain homeostasis
What is the “Obligatory urine volume”?
The minimal volume of urine that must be excreted
Excretion of solute per day / maximal urine concentrating ability
What is Urine specific gravity?
A measure of the weight of solutes in a given volume of urine + is determined by the number and size of solute molecules
The more concentrated the urine -> the higher the urine specific gravity
ADDITIONAL INFO: Relationship between specific gravity and osmolality is altered when there are significant amounts of large molecules (e.g glucose) which are heavy and give a false concentration
What are the requirements for forming a concentrated urine?
- A high level of ADH = increases permeability of distal tubules and collecting ducts to water -> allow tubular segments to reabsorb water
- A high osmolarity of the renal medullary interstitial fluid = provides osmotic gradient necessary for water reabsorption to occur in presence of high levels of ADH
What is the Countercurrent mechanism?
The mechanism by which the renal medullary interstitial fluid becomes hyperosmotic
It depends on:
- special anatomical arrangement of the loops of Henle
- vasa recta
What factors contribute to the buildup of solute concentration into the renal medulla?
- Active transport of Na2+ and co-transport of K+, Cl- and other ions out of thick portion of ascending limb of loop of Henle into the MEDULLARY INTERSTITIUM
- Active transport of ions from collecting ducts into the MEDULLARY INTERSTITIUM
- Facilitated diffusion of urea from INNER MEDULLARY COLLECTING DUCTS into the MEDULLARY INTERSTITIUM
- Diffusion of small amounts of water from MEDULLARY TUBULES into MEDULLARY INTERSTITIUM
What are the steps involved in causing Hyperosmotic renal medullary interstitium?
1) Loop of Henle is filled with a concentration of 300 mOsm/L, the same as that leaving the PROXIMAL TUBULE
2) Active ion pump in THICK ASCENDING LIMB on loop of Henle reduces concentration inside tubule (200) + raises interstitial concentration (400)
3) Tubular fluid in the DESCENDING LIMB OF THE LOOP OF HENLE + interstitial fluid reach osmotic equilibrium due to osmosis of water out of DESCENDING LIMB
4) Hyperosmotic fluid formed in DESCENDING LIMB flows into ASCENDING LIMB
5) Once fluid is in ASCENDING LIMB, additional ions are pumped into interstitium with water remaining in tubular fluid (interstitial fluid osmolality is 500)
6) Fluid in DESCENDING LIMB reaches equilibrium with hyperosmotic medullary interstitial fluid (500)
7) As fluid flows from the descending to the ascending limb, more solute is continuously pumped out + deposited into medullary interstitium
Steps repeat over and over again until fluid osmolality reaches around 1200-1400 -> “COUNTERCURRENT MULTIPLIER”
What are the roles of the distal tubule and collecting ducts in excreting concentrated urine?
Distal tubule = Dilutes tubular fluid since actively transport NaCl out of tubule but is relatively impermeable to H2O
Collecting ducts = In presence of ADH, collecting ducts become highly permeable to H2O which reabsorbs into cortex interstitium
EXPLANATION:
The fact that the large amounts of water are reabsorbed into the cortex, rather than the renal medulla helps to preserve high medullary interstitial fluid osmolarity
What are the steps of Urea reabsorption?
1) As water flows up the ASCENDING LOOP OF HENLE and into the DISTAL and CORTICAL COLLECTING TUBULES, little urea is reabsorbed since segments are impermeable to urea
2) In presence of high ADH, water is reabsorbed rapidly but not urea since CORTICAL COLLECTING TUBULE is not permeable to urea
3) Urea transporters in INNER MEDULLARY COLLECTING DUCT (UT-A1, UT-A2 + UT-A3[activated by ADH]) allow for urea to be reabsorbed, but not as much as water -> High concentration of urea in urine
ADDITIONAL INFO: Urea is transported PASSIVELY by DIFFUSION
What happens to Urea in the early nephron?
- In Proximal tubule, 40-50% if filtered urea is reabsorbed
[concentration in tube still increases since water is more permeable] - Concentration rises since there is passive secretion of urea into the THIN LOOPS OF HENLE by UT-A2
ADDITIONAL INFO: Urea circulation provides an additional mechanism for forming a hyperosmotic renal medulla
What features of renal medullary blood flow contribute to the preservation of the high solute concentration?
- Medullary blood flow is low
[sufficient to supply metabolic needs of tissues but helps to minimise solute loss from the medullary interstitium] - Vasa recta serve as countercurrent exchangers
[minimise washout of solutes from the medullary interstitium]
How does the countercurrent exchange mechanism work?
1) Blood enters and leaves the medulla by the VASA RECTA at the boundary of the cortex and renal medulla
2) As blood descends into medulla, it becomes more concentrated (due to solute entry from interstitium + loss of H2O)
3) As blood descends back towards cortex, it becomes less concentrated as solutes diffuse back into medullary interstitium + water moves into VASA RECTA
EXPLANATION: Vasa recta do not create the medullary hyperosmolarity but do prevent it from being dissipated
What reduces urine concentrating ability?
- Vasodilators
- Large increases in arterial pressure
EXPLANATION: Both increase renal medullary blood flow with “wash out” solutes from the renal medulla which decreases the ability of H2O to flow out into the intersitium -> decreases urine concentrating ability
Where does the urea absorbed into the medullary interstitium from the collecting ducts diffuse into?
The ascending loop of Henle
EXPLANATION: returns the urea to the tubular system + prevents its washout from renal medulla
What is the equation to calculate Osmolar clearance?
C = U X V / P
C - osmolar clearance
U - urine osmolarity
V - urine flow rate
P - plasma osmolarity
What is Free water clearance?
The rate at which solute-free water is excreted by the kidneys. When +ve, excess water is being excreted by the kidneys. When -ve, excess solutes are being removed from blood by the kidneys and water is being conserved.
[difference between water excretion (urine flow rate) and osmolar clearance]
C = V - (U X V / P)
V - urine flow rate
U - urine osmolarity
P - plasma osmolarity
Which abnormalities can lead to the impairment of urine concentrating ability?
- Inappropriate secretion of ADH
[either too much or too little] - Impairment of the countercurrent mechanism
[a hyperosmotic medullary interstitium is required for maximum urine concentrating ability] - Inability of the distal tubule, collecting tubule and collecting ducts to respond to ADH
What is “Central” diabetes insipidus?
An inability to produce or release ADH from the posterior pituitary which can be caused by head injuries, infections or can be congenital
CONSEQUENCES:
- distal tubular segments cannot absorb H2O in absence of ADH -> large amounts of dilute urine + thirst mechanism
- Severe dehydration can rapidly occur if not enough fluid intake
TREATMENT:
administration of ADH analog “DESMOPRESSIN” which acts on V2 receptors to increase water permeability in distal and collecting tubules
What is “Nephrogenic” diabetes insipidus?
When there are normal/elevated levels of ADH but the renal tubular segments do not respond accordingly
CAUSES:
- failure of countercurrent system to form a hyperosmotic renal medullary interstitium
- failure of the distal and collecting tubules and collecting ducts to respond to ADH
CONSEQUENCES:
- large amounts of dilute urine + thirst mechanism
- severe dehydration if not enough fluid intake
TREATMENT:
- nephrogenic diabetes insipidus can be distinguished from central diabetes insipidus by administration of DESMOPRESSIN -> lack of prompt decrease of urine output within 2 hours -> diagnosis
- correct underlying renal disorder for treatment
