Physiology 335 Exam 4A (Renal Physiology)
Describe the role of Bowman's Epithelium in determining the composition of the filtrate
(podocytes)- travel through filtration slit
What is Diabetes insipidus?
(water diuresis) caused by the failure of the axons with cell bodies in the hypothalamus and synapses on blood vessels in the posterior pituitary to synthesize or release vasopressin = central OR inability of the kidney to respond to vasopressin = nephrogenic; permeability of water in collecting ducts is low (even when dehydrated) and there will be increased water loss- large volume of urine that is watery
Describe the cortical nephron
- Short or NO Loops of Henle - Do NOT contribute to hypertonic medullary interstitium (because of short loop)
Describe the juxtamedullary nephron?
-long loops of Henle that go down into depths of the medulla -play important role in regards to environment in medulla (generate gradient) -important for water reabsorption -Peritubular capillaries are called the vasa recta (straight)
What are the three layers composing the glomerular filtration barrier?
1) Capillary endothelium 2) Basement membrane 3) Bowman's Epithelium
two possible routes of tubular reabsorption
1) Diffusion (lipid soluble substances that don't need carriers) via paracellular transport 2) Mediated Transport (of large/charged substances...like glucose) via transcellular transport
List four basic facts related to tubular secretion.
1) Foreign chemicals, drugs, toxins, hormones, K+, H+ will be secreted so that they can be excreted 2) Usually involves active transport (coupled to Na+ reabsorption) 3) Most secretion occurs within the proximal tubules (except for K+ is secreted into distal tubule and cortical collecting duct) 4) Secreted substances can have a Tm (transport maximum) too!
What are the three basic renal processes of the kidney?
1) Glomerular Filtration 2) Tubular Secretion 3) Tubular Reabsorption
SODIUM REABSORPTION IN Proximal Tubule
1) Has primary active transporter (red) on basolateral membrane, secondary active transporters (blue) on apical membrane, and facilitated diffusion carrier (green) 2) Glucose, amino acids, etc. are cotransporter with Na+ into the proximal tubule 3) Hydrogen is secreted into the tubular lumen via counter transport with Na+ into the proximal tubule 4) 65% of Na+ reabsorption occurs here and is non-regulated (occur automatically without hormones) 5) Reabsorption of Na+ and water are coupled
SODIUM REABSORPTION IN THE Ascending limb of the Loop of Henle
1) Has primary active transporters on basolateral membrane and secondary active cotransporter on apical membrane 2) Notice the potassium recycling to drive the transporter (NKCC), 3) 25% of Na+ reabsorption occurs here and is non-regulated
What are the components of the JGA?
1) Juxtaglomerular(JG) cells (wraps around afferent arteriole) 2) Macula dense (part of the distal convoluted tubule) 3) Holds important functions in the regulation of ion and water balance, and the production of factors that control blood pressure. 4) Found near the end of the ascending limb of each Loop of Henle
What are the organs that comprise the urinary system?
1) Kidneys 2) Ureter 3) Bladder 4) Urethra
SODIUM REABSORPTION IN THE Cortical Collecting Duct
1) Na+ reabsorption occurring here is regulated by aldosterone (more aldosterone = more pumps/channels= more sodium reabsorption), 2) Aldosterone is what builds Na+ and K+ channels and Na+/K+ ATPase pumps 3) Primary active transporter on basolateral membrane and channels on the apical membrane 4) Na+ not directly coupled to water reabsorption in the cortical collecting duct
20. Compare and contrast the main routes for water reabsorption in the proximal tubule vs. in the collecting ducts.
1) Proximal tubule water reabsorption through paracellular transport, aka diffusion through tight junctions and is not regulated (high and constant) 2) Collecting ducts water reabsorption through transcellular transport with insertion of aquaporins (regulated by ADH), make cells more permeable to water, variable and requires the renal medullary gradient
What are some examples of things that utilize tubular reabsorption?
1) Substances that are Partially Reabsorbed/Secreted= Na+, Cl-, Water are all substances that must be in maintenance within a homeostatic range 2) Substances that are 100% Reabsorbed= Glucose, Amino acids very important for health
24. Describe how aquaporin type 2 (AQP2) gets inserted into the apical membrane of a collecting duct cell.
1) Vasopressin binding to its receptor on the basolateral membrane 2) Activates intracellular signaling cascade to turn on adenylate cyclase to increase intracellular cAMP 3) More cAMP increases the activity of the enzyme protein kinases A (PKA) 4) More PKA means more phosphorylation of specific proteins that allow for the membrane fusion containing AQP2 with the apical membrane 5) this leads to an increase in the number of AQP2 channels in the apical membrane and allows for passive diffusion of water into the cell **Water exits through AQP3 and AQP4, which are not vasopressin sensitive**
What is the average value of GFR?
125mL/min (180 L/day), (meaning- body can have 3L of blood plasma meaning that is filtered 60X a day!)
RPCs
= clearance of substance (mL/min)
Explain how the ACE inhibitors reduce reduce hypertension.
ACE inhibitors would block out the Angiotensin-converting enzyme from being able to convert Angiotensin I to Angiotensin II. This will reduce arteriole constriction and promote blood volume reduction to decrease blood pressure. It will also cause Na+ and water excretion to decrease blood pressure and increasing renin secretion.
Describe the drug that blocks aldosterone receptors to reduce hypertension
Aldosterone receptor blockers will cause a blockage to aldosterone in the kidney's cortical collecting ducts from being able to retain and reabsorb water and salt, decreasing the blood pressure and increasing renin secretion. Angiotensin II will be blocked up and increase.
Describe the drug that blocks angiotension II to reduce hypertension
Angiotensin II blockers will block the biologically active Angiotensin II from telling the adrenal cortex to secrete aldosterone (causing reduced arteriole constriction and promoting blood volume reduction to decrease the patients' blood pressure). Similar Na+ effects above as well. Buildup of ACE.
31. Discuss the effects of atrial natriuretic peptide on the renal handling of Na+.
Atrial natriuretic peptide does the opposite effects of aldosterone (so it wants to put Na+ into the urine!) Stimulus would be an increase of total body sodium, leading to an increase of BP and plasma volume. Negative feedback loops from Na+ excretion, to increased urine volume, to decrease plasma volume would occur.
What does caffeine due to GFR?
Caffeine dilates the afferent arteriole, why caffeine is a diuretic and increases urine excretion (increases GFR)
Describe why total body NaCl is proportional to ECF volume.
Due to the fact that most Na+ (Cl) will be found in the ECF volume due to the Na+/K+ ATPase pumps, most salt will stay in the ECF and water will always follow the salt. Water can diffuse through cell wall into the ICF, but salt will stay in the ECF. NaCl and water losses equal NaCl and water gains, and no net change in body NaCl and water occurs.
BICARBONATE IS THE MAJOR
ECF BUFFER OF H+ (MAINTAINS BLOOD PH OF 7.4)
35. Explain why maintenance of ECF [K+] is critical for survival.
ECF controlled by Kidneys; ICF controlled by Na+/K+ ATPase Pumps! Although only 2% of total body potassium is in the extracellular fluid, the K+ concentration in this fluid is extremely important for the function of excitable tissues, notably nerve and muscle. Resting membrane potentials of these tissues largely depend on the concentration of K+ across the plasma membrane. Consequently, either increases (hyperkalemia) or decreases (hypokalemia) in extracellular K+ concentration can cause abnormal rhythms of the heart (arrhythmias) and abnormalities of skeletal muscle contraction and neuronal AP conduction.
Define and write the equation for the filtered load
Filtered Load = GFR x [P]s (plasma concentration) Total amount of any nonprotein or non-protein-bound substance into Bowman's space
State the percentage of the filtrate volume that is typically reabsorbed,
Filtered loads are HUGE! BUT ~ 99% of filtered volume is REABSORBED
RPCinulin=
GFR (inulin is not naturally produced, needs to be injected, 20% goes into Bowman's Space, water reabsorbed but not inulin, inulin is not reabsorbed or secreted, low here means kidneys are filtering like they should be)
RPCcreatine=
GFR (naturally produced, same things as inulin, freely filtered, not reabsorbed, secreted~10%, produced by muscles at a constant rate)
29. Describe how renin acts as part of a negative feedback loop to regulate blood pressure, and indicate where, along the nephron, hormonal regulation of Na+ normally occurs.
Hormonal regulation of Na+ normally occurs within the cortical collecting ducts (by aldosterone), Look at RAAS above too., Negative feedback: increasing the blood pressure at the end is a negative feedback loop to the top of this diagram to the left, will intern increase plasma volume and will cause less renin to be secreted)
Describe the last mechanism showing the renal handling of HCO3- and H+
If excess of H+, as if typical = after all filtered bicarbonate is gone, secrete H+ via ammonium, net gain of NEW bicarbonate!
Describe one of the other different mechanisms showing the renal handling of HCO3- and H+
If excess of H+, as if typical = after all filtered bicarbonate is gone, secreted H+ combines with non-bicarbonate buffer molecules, net gain of NEW bicarbonate
25. Describe how the presence of ADH/vasopressin along with the renal medullary gradient are used to concentrate the urine.
In the presence of ADH, the hyperosmotic medullary ISF allows for urine to become highly concentrated with a very low volume because we've reabsorbed all the water out of the collecting ducts (medullary) and allowed for it to enter the blood vessels of the medulla to be carried away. (ADH also increases urea absorption)
WHAT are the two types of nephrons in a human kidney and which type is more numerous?
Juxtamedullary (15%) & Cortical (85%)
36. Describe the basic processes, as well as the channels, pumps, and transporters involved, in the renal regulation of potassium at the level of the proximal tubule, the ascending limb of the loop of Henle, and the cortical collecting duct, and explain where hormonal regulation of potassium normally occurs.
K+ is considered to be freely filtered, K+ reabsorption is in proximal tubule/Loop of Henle, Some K+ secretion occurs when diets have normal amount of K+
What is the definition of tubular secretion?
Movement of substances from the peritubular capillaries to the tubular lumen
Draw a graph depicting the filtered load, reabsorption rate, and excretion rate for various concentrations of plasma glucose. Identify where the transport maximum (Tm) is reached, and explain what is meant by Tm.
Normally, glucose is below the transport maximum, but if you increase the filtered load of glucose and it exceeds the glucose transport maximum for a significant number of nephrons, then glucose will need to be excreted and will be seen in the urine.
28. Describe three different inputs to juxtaglomerular (JG) cells, which lead to an increase (or a decrease) in the secretion of renin.
Notice the increased sympathetic activity, Decreased blood pressure, And decreased fluid volume, GFR, NaCl delivery ALL cause an increase in renin secretion. , **REDUNDANT CONTROL OF RENIN**
List the output variable that is normally altered to balance loss with gain.
Output variable that is the main regulator of sodium levels (and water) is the urinary output of the body.
Distinguish between the four types of acid-base disorders, and identify the causes and compensations for each disorder.
PAGES 40-41 FOR THE DISORDERS!!
Where does the largest amount of K+ reabsorption occur?
Proximal tubule (65% here)
Filtrate is blood plasma minus _______
RBCs and proteins
Define and write the equation for renal plasma clearance (RPC).
RPC = the volume of plasma per unit time from which all of a substance is completely removed ("cleared") by the kidneys and excreted in the urine.
RPCPAH=
Renal plasma flow (want to see how blood is flowing into the kidneys to begin with, organic anion not naturally produced, will be injected, freely filtered and actively secreted so that none is left in blood plasma)
What are some examples of things that use tubular secretion?
Substances 100% Secreted = Drugs and toxins, potentially harmful to the body
27. Describe all of the components of the renin/angiotensin/aldosterone system.
Summary of the renin-angiotensin system and the stimulation of aldosterone secretion by angiotensin II. Angiotensin- converting enzyme (ACE) is located on the surface of capillary endothelial cells. The plasma concentration of renin is the rate- limiting factor in the renin-angiotensin system; that is, it is the major determinant of the plasma concentration of angiotensin II. Renin is synthesized and stored from JG cells that surround the afferent arteriole
Discuss the most prevalent mechanisms and molecules for the buffering of hydrogen ion in the body.
The carbonic acid buffering system, respiration will rapidly adjust pH via changes in CO2 levels. Kidneys adjust pH slowly via bicarbonate concentration changes (HCO3-)
22. Describe how urea recycling contributes to the renal medullary gradient.
The recycling of urea "traps" urea in the inner medulla, thus increasing osmolarity and helps maintain hypertonicity. (By being reabsorbed, secreted and reabsorbed again).
21. Define the renal medullary gradient, and explain how it is created by the countercurrent multiplier system involving the long loops of Henle.
The renal medulla has a concentration gradient with low osmolarity superficially and a high osmolarity at its deepest point (as you travel deeper into the medulla towards the renal pelvis). Only the juxtamedullary nephrons with their long loops create this gradient, but all nephrons flow through it. As you travel down the descending limb of the loop of Henle is highly permeable to water, and does not reabsorb the NaCl being pumped out by the ascending limb...therefore it is going to pump out water towards the concentrated ISF until the osmolarities inside the limb and the ISF are equal. Causes the ISF of the medulla to become concentrated and multiplied. (ascending limb is impermeable to water)
23. Explain how the vasa recta function to maintain the renal medullary gradient.
The vasa recta maintain the hypertonic interstitial renal medulla, through the movement of water and solutes through diffusion. In the descending limb of vasa recta water is secreted out and solutes are taken in to build the osmolarity. In the ascending limb of vasa recta water is taken in and solutes are secreted out. This prevents the washing out of the gradient set up by the loops of Henle. It minimizes excessive loss of solute from the interstitium by diffusion and carried away in equivalent amounts by bulk flow.
Describe one of the different mechanisms showing the renal handling of HCO3- and H+
To keep pH normal: kidneys must recover a huge amount of filtered bicarbonate. For every 1 bicarbonate filtered, there will be 1 bicarbonate reabsorbed back into capillaries...no net change!
Define and write the equation for the excreted load
V (rate of urine formation) x [U]s (concentration of whatever substance in the urine) EL < FL, net reabsorption occurred, if EL> FL, net secretion occurred
32. Describe the neuronal control of ADH/vasopressin secretion (via osmoreceptors and baroreceptors), and thus regulation of water reabsorption, maintenance of osmolarity, hydration status, and blood pressure.
Water regulation in the collecting ducts host regulated amounts of ADH/vasopressin due to the aquaporins within the luminal membranes. The MAIN function of ADH is to regulate plasma osmolarity via the osmoreceptor reflex. Stimulus can be seen as amount of water ingested! Notice if we drink too much water, vasopressin secretion will be decreased because we don't need to reabsorb all of that water. The opposite events will occur when osmolarity increases (with dehydration)...the baroreceptor reflex for vasopressin (much lesser role under most physiological circumstances) allows for the reabsorption of water when plasma volume decreases (this will also turn on the RAAS cascade for sodium reabsorption)
What is the juxtaglomerular apparatus?
a system that regulates the rate of filtrate formation and systemic blood pressure
What are things that can be filtered in the kidney into Bowman's space?
call constituents of blood that can be freely dissolved, cell-free, except for large proteins, low molecular weight solutes appear (drugs, glucose, amino acids, Na+, Cl+, Water)
If you constrict the afferent arteriole you will
decrease glomerular capillary blood pressure and decrease GFR
If you dilate the efferent arteriole you will
decrease glomerular capillary blood pressure and decrease GFR
What is the definition of glomerular filtration?
filtrations of plasma from the glomerular capillaries into Bowman's space, filtrate is glomerular filtrate
If you constrict the efferent arteriole you will
increase glomerular capillary blood pressure and increase GFR
If you dilate the afferent arteriole you will
increase glomerular capillary blood pressure and increase GFR
Describe the role of the capillary endothelium in determining the composition of the filtrate.
leaky pores, cause large flow of fenestrate, cells and plasma proteins too big for filtration through though
What is contained within the renal medulla of the kidney?
long Loops of Henle and collecting ducts
What occurs at the cortical collecting ducts in terms of K+?
normally there is K+ secretion from this tubular segment
What occurs at the ascending Loop of Henle in terms of K+?
normally there is net K+ reabsorption here, about 20% of total
Ps=
plasma concentration of substance (mg/mL)
Describe the role of the basement membrane in determining the composition of the filtrate
proteinosis layer with negative charge, excluding plasma proteins
What does Aldosterone do in basic renal processing?
regulates ion movement by building pumps and channels (to increase pumping into cells and diffusion of K+ into the tubular lumen)
What is contained within the renal cortex of the kidney?
renal corpuscles, convoluted tubules, cortical nephrons
What are the regions of a kidney?
renal cortex is the outer rim outside the pyramids, renal medulla in the inside part
What is the definition of tubular reabsorption?
substance from the tubule back into the peritubular capillary
RPC <GFR
substance is reabsorbed or partially filtered (some of substance bound to plasma proteins)
RPC > GFR
substance is secreted
What is diabetes mellitus?
sugar diabetes (osmotic diuresis) or increased urine flow is the result of a primary increase in the solute excretion. Specifically, glucose has escaped reabsorption because of the huge filtered load retains water in the lumen, causing it to be secreted along with the glucose. Large volume of urine excreted.
Us=
urine concentration of substance (mg/ML)
V=
urine volume per unit time (mL/min)
What is glomerular filtration rate (GFR)?
volume of fluid filtered by glomerulus into Bowman's space per unit time
Filtrate can contain
water, electrolytes, amino acids, glucose, fatty acids, vitamins, urea, uric acid, creatinine
