Renal Phys 2 Flashcards
Kidney regulation of water homeostasis - The kidney is responsible for
The regulation of water balance and is he major route for elimination of water from the body
Kidney regulation of water homeostasis - When water intake is low or water losses increase - the kidney
Conserves water by producing a small volume of urine that is hyperosmotic with respect to plasma
Kidney regulation of water homeostasis - When water intake is high, the kidney produces
A large volume of hypoosmotic urine
Kidney regulation of water homeostasis - The kidney can form urine that is ___ or ____
More concentrated or diluted than plasma
Osmotic pressure - Osmosis
The movement of water across cell membranes occurs by the process of osmosis
The driving force for this movement is osmotic pressure difference across the cell membrane
Osmotic pressure - Osmolarity =
The total concentration of all solutes in the solution
Thus a solution containing 1 mmol/L of solute particles exerts an osmotic pressure of 1 milliosmole/L
Osmotic pressure - Osmolarity and Osmolality are
Frequently confused and interchanged incorrectly
Osmolarity = number of solute particles per 1 L of solvent
Osmolality = number of solute particles in 1 kg of solvent
The unit is different!
Osmotic pressure - Osmolarity vs. Osmolality (for dilute solutions…)
For dilute solutions, the difference between osmolarity and osmalality is insignificant
Water reabsorption along the nephron - step 1 water diruesis
Fluid entering the descending thin limb of the loop of henle from the proximal tubule is isosmotic with respect to plasma
This state reflects the essentially isoosmotic nature of solute and water re-absorption in the proximal tubule
Water reabsorption along the nephron - Step 2 - (water diruesis ) - Water will be re absorbed by the
Water will be re absorbed by the thin descending limb
Water is being reabsorbed in the tubule, but Na is not
Osmolality is increased
Water reabsorption along the nephron - Step 3 to 4 water diruesis
The ascending limb is impermeable to water and actively reabsorbs salt (NaCl) from the tubular fluid and thereby dilutes
This segment is often referred to as the diluting segment of the kidney. Fluid leaving the thick ascending limb is hypoosmotic with respect to plasma
Water reabsorption along the nephron - Step 5-7 water diruesis
Distal tubule and collecting duct actively reabsorb NaCl
In the absence of ADH these segments are slightly permeable to water
Thus when ADH is absent or present at low levels, the osmolarity of tubule fluid in these segments is reduced further because NaCl is re absorbed without water
Under this condition, fluid leaving the collecting duct is hypoosmotic with respect to plasma
Water reabsorption along the nephron - antidiruesis - step 1 to 4
Steps similar to those for production of dilute urine
Re absorption of NaCl byt he ascending limb of the loop of henle dilutes the tubular fluid, the re absorbed NaCl accumulates in the medullary interstitium and raises the osmolarity of this compartment
The accumulation of NaCl in the medullary interstitium is crucial for the production of urine hyperosmotic to plasma because it provides the osmotic drivign force for water re absorption by the collecting duct
Water reabsorption along the nephron - antidiruesis - step 5 to 7
Because of NaCl re absorption by the ascending limb of the loop of henle, the fluid reaching the collecting duct is hypoosmotic with respect to the surrounding interstitial fluid
Thus an osmotic gradient is established across the collecting duct
In the presence of ADH which inc the water premablity of the distal tubule and collecting duct, water diffuses out of the tubule lumen and tubule fluid osmolarity increases
This diffusion of water out of the lumen of the collecting duct begins the process of urine concentration
The kidney regulates the content of water in the urine - the basic mechanisms to re absorb water and form concentrated urine are:
High level of ADH
High osmolarity of renal medullary interstitial fluid - Concurrent mechanisms, Urea recycling
ADH
An increase in fluid osmolarity caused the osmoreceptor cells to shrink
Shrinkage of the osmoreceptor cells signals the supraoptic nuclei or the pituitary gland that release ADH into the bloodstream
When ADH reaches the kidney, it controls the degree of urine concentration
ADH feedback mechanism – with deficit in water
With deficit of water ingestion and inc in extracellular fluid osmolarity, ADH secretion is inc and water is conserved in the body
ADH feedback mechanism – with excess of water
with excess of water ingestion and a decrease in extracellular fluid osmolarity, less ADH is formed, the renal tubules decrease permeability to water - less water is reabsorbed and a large volume of urine is formed
Role of thirst in controlling ECF osmolarity
When body fluid osmolarity is increased a person perceives thirst
Hypothalamus contains thirst osmoreceptors that sense ECF osmolatiry (thirst center)
These cells stimulat hypothalamic neurons causing thirst and icnreased water intake in response to hyperosmolality
Osmoreceptor ADH and thirst mechanism work in parallel to precisely regualte ECF osmolarity
In absense of ADH thirst mechanisms, no other feedback mechanism is capable to adequately regulate ECF osmolarity
Stimuli of thirst
Large dec in circulating blood volume and/or BP
Hemorrhage
Dryness of mouth and throat
Thirst mechanisms are temporarily suppressed after drinking water - if insufficient water was drunk, the person becomes thirsty again until the ECF osmolarity is returned to normal
Disorders of urinary concentration ability
Inappropriate secretion of ADH
Inability of the renal tubules to respond to ADH
Central diabetes insipidus
Inability to produce or release ADH from the post pit gland results in large volume of diluted urine
THirst mechanisms are activated
Tx - synthetic ADH, desmopressin
Nephrogenic diabetes insipidus
Normal or high ADH, but kidney cant respond to it
Abnormality can be due to failure of countercurrent mechanism to form or failure of renal tubules to respond to ADH
Large volume of diluted urine are formed
Tx - correct the underlying renal disorder
Some drugs can impair kidney response to ADH - diuretics, lithium, tetracycline
High osmolarity of the renal meduallary interstitial fluid - countercurrent mechanisms
Two countercurrent multiplication mechanisms operate in the renal meduallary interstitium to re absorb water from collecting duct
1 Countercurrent multiplier in the loop of henlt
2 Countercurrent exchanger in the vasa recta
High osmolarity of the renal meduallary interstitial fluid - countercurrent mechanisms - Countercurrent multiplier
Because water mvmnt is passive, driven by osmotic gradient - they kidney must generate hypeosmotic compartment which then drives osmotically water re absoprtion from the colelcting duct
The hyperosmotic compartment in the kidney is the interstitial space of the renal medulla around the loops of henle
High osmolarity of the renal meduallary interstitial fluid - countercurrent mechanisms Countercurrent exchanger
NaCl diffuses out of the ascending limb of the vessel and into the descending limb
Water diffuses out of the descending and into the ascening limb of the vascular loop
Mechanisms of regulation
Local control (renal auto regulation)
Hormone control
Nervous control
Renal auto regulation
BP changes throughout day - we want renal pressure to stay same though
Kidney regulates fluid and electrolytes homeostasis by modulating the relationship between the glomerulus and tubule of the same nephron
The tubule responds to a change in the glomerulus with the glomerulotubular balance
The glomerulus responds to a change in the tubule through the tubuloglomerular feedback
Renal autoregulation - Tubuloglomerular feedback (TGF)
Enables the function of a glomerulus to compensate to fluctuation in NaCl concentration in the tubule of the same nephron
Fluctuation in NaCl is sensed at level of juxtaglomerular apparatus
Apparatus consists of macula densa cells in distal portion and juxtaglomerular cells in wall of arterioles
TGF control GFR by a feedback mechanism acting on the renal arteriolar resistance
Renal autoregulation - Control of GFR by the TGF
When the GFR increases, and causes Nacl concentration of tubular fluid at the macula densa to rise, more NaCl enters the macula densa cells
The signal causes VC of the afferent arteriole which retruns the GFR to normal level (dec it)
Hormoneal control
Precise regulation of body fluid volumes and electrolytes concentrations require kidney to excrete different solutes and water at variable rates
SEVERAL hormones provude this specificity of tubular reabsoprtion and secretion
- ADH
- Renin, Angiotensin II, Aldosterone
- Natriuretic peptides
Mechanisms of renin relese - Perfussion pressure
When perfusion pressure to the kidneys is reduced, renin secretion by the afferent arteriole is stimulated
Conversely, an inc in perfusion pressure inhibits renin releease by the afferent arteriole
Renin is secrete by juxtaglomerular cells
Mechanisms of renin release - Sympathetic nerve activity
Activation of sympathetic nerve fibers tha tinnervate the afferent arterioles inc renin secretion via B adrenergic receptor stimulation
Renin secretion is dec as renal symp nerve activity is dec
Mechanism o frenin release - Delivery of NaCl to macula densa
When NaCl delivery ot the macula densa is dec, renin secretion is enhanced
Inc in NaCl delivery inhibits renin secretion
Mechanisms of renin release
Perfussion pressure
Sympathetic nerve activity
Delivery of NaCl to macula densa
Feedback control of macula densa
Macula densa is located in the loop of henle - it will sense the NaCL delivery and in response it modulates two different processes in parallel
TGF
Renin secretion
Angiotensin II synthesis and function - Renin functions as a
proteolytic enzyme
Its principle substrate is angiotensinogen
Angiotensinogen is cleaved by renin to angiotensin I that is further cleaved to angiotensin II by a coverting enzyme
Angiotensin II synthesis and function -
Stimulation of aldosterone secretion by the adrenal cortex
Renal arteriole VC
Direct enhancement of NaCl reabsorption at the level of several nehron segments
Angiotensin II regualtes BP
Aldosterone is secreted by
Zona glomerulosa cells of the adrenal cortex
Aldosterone acts on
th cells of the collecting duct o inc Na re absorp and K secretion
Na and K intakes affect the level of aldosterone
High Na intake dec while High K intake increases plasma aldosterone
In the clinic - impaired aldosterone secretion associates with defects in regulation of
Na and K concentration Adrenal destruction or malfunction (addisons disease) Adrenal tumors (Conns syndrome)
Natriuretic peptide
Heart produces two natriuretic peptides
Atrial myocytes produce and store the atrial natriuretic peptide and ventricular myocytes produce and stroe brain natriuretic peptide
Both peptides are secreted in response to myocardial wall stretch and they act to promote NaCl and water excretion by the kidney
Natriuretic peptide - Both peptides are secreted in response to myocardial wall stretch and they act to promote NaCl and water excretion by the kidney -
1 Direct inhibition of NaCl reabsorption by the collecting duct
2 Inhibition of ADH secretion and action on the colelcting duct - dec water re absorption by the colelcting duct and therefore inc excretion of water in the urine
3 Afferent arteriole VD and efferent arteriole VC with glomerulus - inc GFR and filtered amount of Na
Nervous control
Kidney BVs are richly innervated by sympathetic nerve fibers
Renal symp nerve activity is minimal when volume of ECF is normal - when ECF declines, symp nerve activity rises dramatically
Nervous control - an icnrease in activity of symp nerves results in
An increase of NaCl and water re absoprtion due to
1 Reduction in GFR by VC of renal arterioles
2 Inc tubular NaCl reabsoprtion
3 Inc in renin release and angiotensin II formation which further stimulates tubular NaCl re absoprtion
Renal response to volume contraction
The renin angiotensin aldosterone system is activated
ADH release from post pit gland is stimualted
Symp nerve activity is stimulated
Overall dec in sodium and water secretion
- Dec in GFR
- Inc in Na reabsorption in proximal tubule
- Inc in Na and H20 reabsorption in collecting duct
Renal response to volume expansion
Sodium and fluid retaining mechanisms are decreased
THe increased stretch on the cardiac right atrium releases atrial natriuretic peptide
