Lecture 3: Renal Concentration Mehanisms Flashcards
What is physiologic osmolarity?
~285-300 mOms
Site of Renin Synthesis
Juxtaglomerular Apparatus
What are the 4 components of the Juxtaglomerular Apparatus?
- Motified smooth muscle cells in afferent arteriole
- Modified smooth muscle cells in the efferent arteriole
- Extraglomerular mesangial cells
- Macula densa cells in the distal tubule (effected by Na concentration)
What is the 1st step in the Renin-Angiotensin Pathway?
Renin causes angiotensinogen to be cleaved to angiotensin I.
What is the 2nd step in the Renin-Angiotensin Pathway?
Angiotensin I is converted to angiotensin II in the lung by angiotensin converting enzyme (ACE)
What is the 3rd step in the Renin-Angioensin Pathway?
Angiotensin II is the most potent vasoconstrictor know. BP increases.
Actions of Angiotension
- VasoConstriction and Increased BP
- Increased Aldosterone systhesis and release
- Increased Antidiuretic hormone release (Vasopressin)
- Increased Thirst
- Feedback inhibition of renin release
- Although ATII contsricts both afferent and efferent atrerioles, it releases prostaglandins which act of maintain GFR in spite of it’s constrictive effects.
Where is Aldosterone made?
-Synthesized in the zona glomerulosa of the adrenal cortex.
What stimulates the release of Aldosterone?
- Increased K+ in the ECF
- Angiotensin II
- Decreased Na+ levels
Actions of Aldosterone:
- Acts on the DISTAL TUBULE and COLLECTING DUCTS, to cause K+ secretion and H+ in exchange for Na+.
- Net effect is to get rid of K+ and H+ and conserve Na+
Conn’s Syndrome:
- Aldosterone secreting tumor causes HTN, HyperNAtremia, and HypoKalemia.
- Eventually the increased Na+ load excees distual tubule and collecting duct ability to reabsorb Na+; however K+ excretion continues and this can cause fatal HypoKalemia. (will cause hyperpolarization of nerve and muscle cells).
What substances are involved in the Concentrating and Diluting Mechanisms?
- Antidiuretic Hormone (ADH) aka Vasopressin
- Atrial natriuretic peptide (ANP)
- The countercurrent multiplier
- The role of urea
Why is it important to be able to concentrate or dilute the urine?
- In order for cells to function they must be bathed in ECF with a fairly stable concentration of electrolytes and solutes.
- The kidney is able to excrete excess water by forming a dilute urine
- The kidney conserves water by concentrating the urine.
Why cant we drink seawater?
-sea water has a concentration of 2400 mOsm/L. Since the maximal urine concentration is ~1200mOsm/L, 2 Liters of urine would need to be excreted for every 1 Liter of sea/salt water consumed to excrete the solute. This consuming sea water leads to dehydration.
What is the Obligatory Urine Volume?
- The maximum concentrating ability of the kidney is 1200mOsm/L.
A normal 70kg human must excrete 600 mOsm of solute each day.
600mOsm per day/ 1200 mOsm per Liter= 0.5 Liters per day.
Where is Antidiuretic hormone (ADH) synthesized?
In the Hypothalamus
Where is Antidiuretic hormone (ADH) stored and released from?
The Posterior Pituitary Gland
What stimuli is needed for ADH release?
- Osmoreceptors in the hypothalamus detect increased osmolality in the ECF, this stimulates the release.
- Mechanoreceptors in the atria and aorta will detect decreased volume and stimulate ADH release.
- ATII, fright, nausea, pain, anesthesia, nicotine stimulate release of ADH.
- Alcohol inhibits ADH release
ADH plays a major role in conserving water by concentrating the urine.
How does ADH work?
- Increases permeability of the collecting system to water. Without ADH, water is relatively impermeable to water.
- ADH increases urea permeability in the medullary collecting ducts.
- In order for ADH to work, there must be a gradient. (a Hypertonic interstitium.
What is Urea?
- A by product of amino acid metabolism consisting of 2 ammonia molecules.
- Approx 25-50g/day are made in the liver.
What is the role of Urea in the kidney?
-The medullary interstitium has a high concentration of urea which plays an important tole in generating a hypertonic interstitium.
Where is Urea permeable?
- The inner medulla is permeable to urea only in the presence of ADH and urea diffuses into the interstitium and becomes trapped there.
- The THIN ascending limb is permeable to urea, some diffuses into the tubule and is recycled.
Where is Urea IMpermeable?
-The Thick Ascending Limb (TAL) is impermeable to water and urea.
Urea contributes ___% of the osmolarity of the renal medulla gradient during maximum urine concentrating.
40%
Urea passively diffuses from the medullar collecting duct during water deficits when ____ is present.
ADH
Recycling role in concentrating urine:
Urea is recirculated from the medulla interstitium in to the ___ __ ___ and therefore returned to tubular fluid.
Loop of Henle
The Vasa Recta has 2 functions:
- Remove reabsorbed fluid from the interstitium
2. Minimize solute uptake away from the medulla (maintains medullary hypertonicity)
What is the Vasa Recta?
The are the straight capillaries that surround the Loop of Henle. They play the key role in the countercurrent exchange multiplier.
The Vasa Recta is the distal part of the Efferent Arteriole and eventually reconnects with the systemic venous system.
The counter current multiplier:
-Takes place in the Thin descending and ascending limbs of the Loop of Henle. The Thin descending, ONLY water diffuses passively and is impermeable to ions. Conversely, the Thin Ascending is impermeable to water, and permeable to ions through ATP ion pumps. The ions pumped out of the tubule and into the medullar interstitum creates a salty, hypertonic environment and creates the gradient for water to diffuse passively.
Principal cells in the cortical collecting duct are primarily responsible for:
The principal cells in the cortical collecting duct are primarily responsible for secreting potassium.
They also play a role in the aldosterone-mediated absorption of sodium. The intercalated cells in the cortical collecting duct are primarily responsible for acid-base regulation.
The primary site for parathyroid hormone- and vitamin D-mediated calcium reabsorption is the___.
The principal site of parathyroid hormone- and vitamin D-mediated calcium reabsorption is the distal tubule.
What controls water reabsorption in the distal tubule and collecting duct?
Water reabsorption in the distal tubule and collecting duct are controlled by antiduretic hormone.
Where in the nephron is the majority of sodium reabsorbed?
Sodium is reabsorbed throughout the nephron but the majority of it (about 65%) is reabsorbed in the proximal convoluted tubule.
Renin works to increase systemic blood pressure by increasing the serum concentration of
Angiotensin I
Renin is released by the juxtaglomerular apparatus
__________ is a product of phosphocreatine breakdown in muscle and is normally completely filtered by the kidneys.
Creatinine is a product of phosphocreatine breakdown in muscle and is normally completely filtered by the kidneys.
Because creatinine is not reabsorbed and is secreted in very small amounts, it provides an easy way to assess the glomerular filtration rate by measuring the amount of creatinine in the blood and the amount in the urine.
Sympathetic outflow to the kidneys arises from the
Sympathetic outflow to the kidneys arises from preganglionic fibers from the T8-L1 spinal cord levels.
Fluid that exits the distal renal tubule and enters the collecting duct typically has an osmolality of approximately
The osmolality of fluid leaving the distal renal tubule is approximately 50 mOsm/kg.
Through what range of mean arterial pressures is renal blood flow autoregulated?
Autoregulation of renal blood flow is maintained between a MAP of 50 to 180 mmHg.
Nagelhout pg. 731
Which nerve provides parasympathetic innervation to the kidney?
Vagus
Which spinal segments supply parasympathetic innervation to the ureters?
The S2-S4 nerve segments provide parasympathetic innervation to the ureters.
The Major components of the Nephron include: (5 parts)
The major components of the nephron include: -Bowmans capsule
- proximal tubule
- loop of Henle
- distal convoluted tubule
- collecting duct.
What are the 3 ways in which renin release by afferent arterioles is triggered?
Renin release by the afferent arteriole may be activated by:
- low blood pressure
- increased tubular chloride concentration
- sympathetic stimulation.
What are the functions of atrial natriuretic peptide (ANP) in the renal system?
Atrial natriuretric peptide:
- increases GFR, results in systemic vasodilatation, -
- prevents release of renin
- opposes production and action of angiotensin II, and lowers aldosterone secretion.
What two laboratory tests that can be used to estimate the glomerular filtration rate?
Estimates of the GFR can be obtained by resulting the creatinine clearance from urine and blood creatinine tests.
Or, the best is a 24 hour urine collection (not used often, lengthy and needs to be precise collection)
What is the main indication for radical nephrectomy in adults?
Renal cell carcinoma is the primary indication for radical nephrectomy. It account for 90-95% of renal neoplasms in adults.
The kidneys receive approximately ______% of the cardiac output.
Kidneys receive approximately 20-25% ( 1100-1200 cc blood/minute) of the cardiac output.
What is the approximate glomerular filtration rate in mL/min in a normal, healthy adult?
The approximate glomerular filtration rate is 125 ml/min.
Nagelhout pg 731
Which glycoprotein released by the kidneys stimulates red blood cell production in the bone marrow?
Erythropoietin is a glycoprotein released by the kidneys that stimulates the bone marrow to produce red blood cells.
Which hormone is produced in the hypothalamus, released from the neurohyphosis, and targets the distal nephron?
Antidiuretic hormone (ADH) is a hormone produced in the hypothalamus, released from the neurohypophysis (posterior pituitary) and targets the distal nephron. ADH increases tubular permeability causing the reabsorption of water. In the absence of ADH, the collecting ducts and distal tubule are almost impermeable to water.
Which laboratory test is the most reliable assessment tool for renal function?
Creatinine clearance is the most reliable assessment tool for renal function and is specifically a test of glomerular filtration rate.
What is the fundamental end product of protein metabolism?
The fundamental end product of protein metabolism is urea.
It is formed in the liver and excreted through glomerular filtration.
