Ch 26-29 Urine Formation & Electrolyte Regulation Flashcards
What percentage of blood flow do the kidneys require?
About 22%
With which region of the kidney tubules is the macula densa associated?
The thick ascending loop of henle (at the end)
What percentage of nephrons are cortical vs juxtamedullary?
20-30% are juxtamedullary
What are the vasa recta?
They are specialized peritubular capillaries in the outer medulla that aid in developing concentrated urine
What is the name of the urinary bladder’s smooth muscle?
detrusor muscle
Describe the pathway of the sympathetic innervation, (hypogastric nerve) of the bladder from SC segment to neuromuscular junction
From L2, to sympathetic chain ganglion, to the body of the bladder, mostly blood vessels. Some sensory innervation to detect pain and fullness
Which is the principle nerve supply of the bladder? What it its pathway?
The pelvic nerves from the sacral plexus at S2 and S3 then split into the sensory and motor nerve fibers. The Sensory fibers detect stretch and synapse on the body, neck, and external sphincter. The motor PSNS fibers terminate at the bladder wall to ganglion cells.
What is the route and function of the pudendal nerve to the bladder?
Innervates skeletal motor fibers, traveling from the pudendal nerve to the external sphincter for voluntary control
What is the ureterorenal reflex?
When a ureter is blocked, the smooth muscle reflexively constricts powerfully, causing pain. The pain impulses cause a sympathetic reflex that causes renal arteriolar constriction to reduce urine production
How is urine propelled through the collecting ducts to the ureter?
It enters the calyces and stretches them, initiating pacemaker activity, which causes further contractions until the urine enters the bladder
In a stepwise description, how does the micturition reflex occur?
- Urine fills bladder and initiates a stretch reflex via sensory stretch receptors in the posterior urethra
- Stretch receptor signals conduct through the pelvic nerves to the sacral SC
- Signals travel back through PSNS fibers via the same nerves.
- If the bladder keeps filling, these reflexes become more frequent and cause greater contractions of the detrusor muscle
- The reflex is self-regenerative until the bladder reaches a strong degree of contraction, until it fatigues and bladder relaxes
- Or if it becomes powerful enough, it causes a reflex traveling through the pudendal nerves to the external sphincter to inhibit it. Only if the brain overrides this will urine NOT exit.
Which brain centers can inhibit or facilitate micturition reflex?
- Pons of the brain stem ( facilitative and inhibitory centers)
- Inhibitory centers in the cerebral cortex
Which nerves are disrupted in overflow incompetence?
Sensory fibers. Then only a few drops are urinated at a time
How does uninhibited neurogenic bladder abnormality develop?
Partial damage in the spina cord or brian stem interrupting inhibitory signals, so facilitative impulses pass continuously down the cord. This keeps the sacral centers so excitable that even small amounts of urine elicit uncontrollable micturition
simply, how do you calculate urinary excretion rate?
Filtration rate - reabsorption rate + Secretion rate
Which factors determine how easily a molecule is filtered at the glomerulus?
Charge (negative charge is more difficult to filter) and size (molecular weight)
How do you calculate GFR?
GFR= Kf x (Pc - Ps- PiG + PiB). Parentheses are equal to net filtration pressure
Which forces comprise net filtration pressure?
glomerular hydrostatic pressure, bowman’s capsule hydrostatic pressure, colloid osmotic pressure of the glomerular capillary plasma proteins, and colloid osmotic pressure of proteins in the bowman’s capsule.
Which forces of filtration oppose vs promote filtration?
opposes: Bowman’s capsule hydrostatic pressure; glomerular capillary colloid osmotic pressure
promote: glomerular hydrostatic pressure. Bowman’s colloid osmotic is basically = 0
How do you estimate Kf?
Kf = GFR/ Net filtration pressure
How does increasing the filtration fraction affect plasma protein levels and glomerular colloid osmotic pressure?
It concentrates the plasma proteins and raises the pressure
What three forces determine glomerular hydrostatic pressure?
- arterial pressure (incr = incr prsr)
- afferent arteriolar resistance (constriction reduces ghr and gfr, dilation increases it)
- efferent arteriolar resistance (3fold constriction reduces gfr, slight constriction increases ghr and gfr)
In order of decreasing resistance, how does vascular resistance change in kidney circulation?
1) renal artery 2) afferent arteriole 3) glomerular capillaries 4) efferent arterioles 5) peritubular capillaries 6) interlobar/intrarenal veins 7) renal vein
What portion of renal blood flow is dedicated to the cortex vs medulla?
cortex gets almost 100%, and 1-2% total blood flow goes to the medulla
Which blood vessels are preferentially constricted by Angiotensin II?
Efferent arterioles are highly sensitive to it. So increased angiotensin II raises glomerular hydrostatic pressure and reduces renal blood flow
When an animal is volume depleted, angiotensin II helps prevent GFR decreases by constricting the efferent arterioles, and the decreased blood flow through peritubular capillaries facilitates increased sodium and water reabsorption to increase blood volume
What is the function of endothelial-derived nitric oxide?
An autocoid, decreased renal vascular resistance, from the vascular endothelium. Basal tone of this allows the kidneys to excrete normal amounts of sodium and water
What is meant by Autoregulation of GFR and renal blood flow?
Blood flow autoregulation in the kidneys maintains a constant GFR despite changes in arterial pressure.
Why do changes in arterial pressure not exert much effect on urine production?
- Renal autoregulation prevents large changes in GFR
- Glomerulotubular balance causes the renal tubules to increase their reabsorption rate when GFR rises
What effect(s) does reduced NaCl sensed by the macula densa have?
- Decreased blood flow resistance in the afferent arterioles to raise GFR back to normal
- Increases renin release from juxtaglomerular cells of afferent and efferent arterioles
How does a high protein diet increase renal blood flow and GFR?
-Amino acids from the high protein meal are reabsorbed at the proximal tubule. Amino acids are reabsorbed with sodium, so this stimulates Na+ reabsorption in the proximal tubules.
-Na+ delivery to the macula densa decreases
-Afferent arteriolar resistance drops in response to the reduced Na+ at the MD
- Renal blood flow and GFR raise
-Therefore Na+ excretion stays stable while increasing excretion of urea from the increased protein metabolism
Briefly, how do you calculate Urinary excretion?
Excretion = Glomerular filtration - tubular reabsorption + tubular secretion
Glom filtration = Glomerular filtration RATE x plasma concentration
What are the primary active transporters in the kidney?
- Na/K ATPase
- H+ ATPase
- H/K ATPase
- Ca ATPase
What are the three major steps required for Na+ net reabsorption from the tubular lumen back to the blood?
- Diffusion across the luminal/apical membrane down an electrochemical gradient established by the Na/K ATPase
- Na+ is transported across the basolateral membrane against an EC gradient by the Na/K ATPase
- Na, water, and other substances are reabsorbed from the interstitial fluid into the peritubular capillaries by ultrafiltration, a passive process driven by the hydrostatic and colloid osmotic pressure gradients
Where and how is most of the glucose that enters the kidney tubules reabsorbed INTO THE CELL?
Where: 90% of filtered glucose is reabsorbed by SGLT2 in the early (S1) segment of the proximal tubule (other 10% is via SGLT 1 in the later segment of the PT).
How: Secondary active transport.
The Sodium glucose co-transporters on the brush border of the prox tubular cells carries glucose against the conc gradient, powered by the energy liberated by sodium moving down its own EC gradient
How is glucose reabsorbed from the tubular cells back into the bloodstream?
Passive facilitated diffusion!
Glucose diffuses out of the cells via the glucose transporters.:
In the S1 segment: GLUT2
In the latter part/S3: GLUT1
How is hydrogen transported from the tubular cell into the tubular lumen?
Via secondary active transport! The sodium-hydrogen exchanger in the luminal membrane carries Na into the cell and forces out H+. Then a Na/K transporter in the basolateral membrane forces out Na and brings K+ intracellularly
How are proteins reabsorbed from the tubular lumen?
By active transport: Pinocytosis!
Protein attaches to the brush border and the membrane invaginates and is digested intracellularly, then its constituents are reabsorbed through the BL membrane
Which substances are actively reabsorbed and have a transport maximum?
Glucose, phosphate, sulfate, amino acids, urate, lactate, and plasma proteins
What is a transport maximum? What is its relevance?
It’s a limit to the rate at which a solute can be transported, created by a limitation in the number of transporters and enzymes available.
Ex// glucose reaches a transport maximum when plasma glucose exceeds the kidney’s ability to actively transport glucose into cells. Not all nephrons have the same transport maximum, so glucose appears in urine before the transport maximum is reached
What other factors, besides transport max, can determine rate of transport?
- electrochem gradient
- membrane permeability
- time that solute-containing fluid spends in the tubule (gradient time transport, determined by flow rate)
How is sodium reabsorption in the proximal tubule an example of gradient time transport?
*Remember a lot of Na transported out of the cell leaks back into the tubular lumen through epithelial tight junctions, and this rate depends on…
-Tight junction permeability
-Interstitial physical forces
SO the greater the conc of Na in the proximal tubules, and the slower the flow rate of tubular fluid, the greater its reabosorption rate
Which hormone can change the transport maximum of sodium in the more distal nephron?
Aldosterone
How does water movement across the tubular epithelium change throughout the nephron?
- Proximal tubule: high permeability, reabsorbed as quickly as the solutes
- Ascending LoH: almost no water is reabsorbed, poor permeability
- Distal tubules, collecting tubules, collecting ducts: high or low, depending on ADH influence
By which types of transport is chloride reabsorbed?
- Passively via paracellular pathway, following EC gradient of Na+
- Secondary active transport: co-transport with Na+
By which types of transport is urea reabsorbed from the tubules?
- Passive reabsorption:
as water is reabsorbed, urea luminal conc increases. Sometimes using passive transporters. Only 1/2 of filtered urea is reabsorbed though
Which characteristics of proximal tubule epithelial cells enable its high reabsorptive capacity?
- Lots of mitochondria to power active transporters
- Extensive apical brush border
- Extensive intercellular and basal channel labrynths
- Lots of protein carrier molecules
Why does the solute reabsorption profile differ from early to late proximal tubule?
Early PT: Na is reabsorbed by co-transport with glucose, AA’s, bicarbonate, and organic ions…this leaves a Cl- rich tubular fluid
Last 1/2 PT: More Cl- means favors diffusion from the lumen to the renal interstitial fluid
Why/how does the total solute osmolarity remain constant along the proximal tubule?
The amount of solute decreases (such as sodium, drops as reabsorbed), but water permeability keeps pace.
**The high permeability to water in this part of the nephron ensures that osmolarity stays relatively constant
How are organic acids and bases handled in the proximal tubules?
Bile salts, oxalate, urate, catecholamines, and many drugs or toxins are secreted here. Recall they were filtered into the proximal tubule at the glomerulus. AND now are rapidly secreted here to rid the body of them via urine
What is the function of the thin descending loop of henle?
-high water permeability (20% of all water reabsorption)
-moderate solute permeability, no active reabsorption
-Simple diffusion through thin walls
What are the functions of the thick ascending loop of henle?
-High metabolic activity in cells
-25% of filtered Na, Cl, and K are reabsorbed here
-Lots of Ca, HCO3, and Mg are reabsorbed here
**Transporters present:
-Na/K ATPase: basolateral side, maintains low intracellular Na to create a gradient for movement of Na from tubular fluid to cell
-Na movement from tubular fluid to cell is mediated by a 1Na/1K/2Cl co-transporter on the apical side
-Also has a Na/H co-transporter moving Na into the cell and H+ secretion into the tubular fluid
-Paracellular reabsorption of Na, K, Mg, and Ca…facilitated by the backleak of K+ that creates a slight positive charge in the tubular fluid, forcing out other cations
NO WATER. Impermeable to water here. So the tubular fluid is very dilute
Where do loop diuretics have effect in the nephron?
Furosemide inhibits action of the Na/K/2Cl co transporter , which makes the tubular fluid here less dilute, which will draw out more water later
Why is the first portion of the distal tubule called the diluting segment?
Which component of this segment is targeted by thiazide diuretics?
It reabsorbs many ions but is impermeable to water or urea, so fluid is very dilute .
Has a Na/Cl co transporter on the apical side, and a Na/K ATPase on the basolateral side for ion transport.
Thiazides inhibit the Na/Cl co-transporter on the luminal side
In which part of the nephron is the juxtaglomerular apparatus?
The early distal tubule: macula densa cells provide feedback and participate in GFR control
What unique cell types exist at the late distal tubule and cortical collecting tubule? What are their jobs?
Two cell types:
1. Principal cells : reabsorb Na and H2O from the lumen and secrete K into the lumen
2. Intercalated cells: reabsorb K and secrete H into the lumen
What are the potassium sparing diuretics, and where/how do they take effect?
They act at the principal cells:
1. Spironolactone and eplerenone = mineralocorticoid receptor antagonists that compete with aldosterone and inhibit aldosterone from stimulating sodium reabsorption and K+ secretion
- Amiloride & triamterene block the sodium channels of the luminal membrane to decrease Na transport into the cell and thus decr K transport into the tubular lumen
What is the function of the intercalated cells? How is this accomplished?
- Hydrogen ion transport via a H+ ATPase
–> H+ and HCO3 are generated in the cell by carbonic anhydrase, so for each H+ secreted, a bicarb is reabsorbed - K+ reabsorption
In 4 brief points, what are the functional characteristics of the late distal tubule and cortical collecting tubule?
- Urea is NOT reabsorbed. Pass on through
- Late distal and cortical collecting tubules reabsorb Na+ and secrete K+, which aldosterone controls.
- Intercalated cells are big for Acid/base balance because they secrete H+ against a conc gradient
- Water permeability is controlled by aldosterone at the late distal tubule
What are the functional/special characteristics of the medullary collecting ducts?
- ADH controls permeability to water and thus urine volume/conc
- Urea transporters allow some tubular urea to be reabsorbed into the interstitium
- Secretes H+ against a conc gradient for acid/base balance
Briefly, what is the glomerulotubular balance?
The ability of the tubules to increase reabsorption rate in response increased tubular flow.
-Helps prevent overloading the distal tubular segments
-The 2nd line of defense to buffer the effects of spontaneous GFR changes on urine output
If reabsorption = Kf x Net reabsorptive force, what is Kf, and what comprises the net reabsorptive forces?
Kf = filtration coefficient, aka capillary ability to reabsorb
NRF is made up of 2 forces that oppose reabsorption, and 2 that support reabsorption:
Opposing:
1. Hydrostatic pressure inside peritubular capillaries
2. Colloid osmotic pressure of the proteins in the renal insterstitium
In favor:
1. Hydrostatic pressure in the renal insterstitium
2. Colloid osmotic pressure of the peritubular capillary proteins
What determines/influences peritubular capillary hydrostatic pressure?
Arterial pressure and resistance of the afferent and efferent arterioles
1) Raised arterial pressure increases PCHP and decreases reabsorption
2) Increased afferent or efferent arteriolar resistance decreases PCHP and increases reabsorption rate
What determines/influences peritubular capillary colloid osmotic pressure?
1) systemic plasma colloid OP. When increased, it increases reabsorption
2) the filtration fraction. When increased, it increases reabsorption
-Increased filtration fraction can result from increased GFR or decreased renal plasma flow
How do pressures in the renal insterstitium relate to rate of reabsorption into the peritubular capillaries?
Forces that increase peritubular cap reabs also incr reabsorption from the renal tubules.
Hemodynamic changes that inhibit peritubular cap reabsorption inhibit tubular reabsorption of water and solutes
How does increased arterial pressure influence urine output?
- Inc BP increases GFR (only slight in healthy kidneys due to autoregulation)
- Incr capillary hydrostatic pressure decreases Na and H2O reabsorption
- Decreased Angiotensin II formation means decr aldosterone secretion, thus decr sodium reabsorption from the tubules
Where does aldosterone act and what is its function?
Where: principal cells of the cortical collecting tubule and duct
Secreted by: zona glomerulosa
How: stimulates Na/K ATPase on the basolateral cortical collecting tubule, so more Na is reabsorbed and more K is excreted, and increases Na permeability on the luminal side
Where does Angiotensin II act and what does it do?
Acts at the prox tubule, thick ascending LoH and distal tubule, collecting tubule
*Also stimulates aldosterone secretion
Increases NaCl and H2O reabsob, increases H+ secretion. Constricts efferent arterioles and directly stimulates Na reabsorption
Where does antidiuretic hormone act, and what does it do?
Act at the V2 receptors of the distal tubule/collecting tubule and duct to increase water reabsorption.
Increases cAMP formation to ultimately stimulate aquaporin installation to increase water reabsorption
Where does atrial natriuretic hormone act and what does it do?
Cardiac atrial cells detect distension/volume expasion
Acts at the distal tubule/collecting tubule and duct to decrease NaCl reabsorption via direct inhibition. Aims to diurese
Inhibits renin secretion and thus AGII formation.
Where does PTH act and what effect does it have?
Site of action: proximal tubule, thick ascending LoH and distal tubule
Decreases phosphate reabsorption and increases Ca reabsorption
Briefly, how does the SNS affect sodium reabsorption?
Increases Na and H2O reabsorption by:
-activating @-adrenergic receptors of the renal tubular cells to increase Na reabsorption in the PT, thick LoH and increases H2O reabsortpion
-constrict renal arterioles and reduce GFR
-Stimulate renin and AGII release
Briefly, what are the two main requirements for creating concentrated urine?
1) ADH secretion
2) Hyperosmolar renal medullary interstitium to pull out water from the tubules (in the presence of ADH)
What are the four major factors that contribute to the buildup of solute concentration in the renal medulla?
1) Active Na transport and co-transport of K, Cl, and etc out of the thick LoH into interstitium . MOST IMPORTANT CAUSE
2) Active ion transport from collecting ducts into medullary interstitium
3) Facilitated diffusion of urea from inner medullary CD’s into the med interstitium
4) Sparse diffusion of water from the medullary tubules into the interstitium (WAY less than solute reabosorption)
How does ADH contribute to/influence the concentration of urine?
ADH increases water reabsorption in the collecting duct and distal tubules, so it takes advantage of the “naturally” hypo-osmotic urine flowing through and saves water from being peed out. Without this, urine would be super-dilute because even more NaCl is reabsorbed in the distal and collecting tubules
Briefly describe the counter current multiplier in the renal medullary interstitium
- Active transport of NaCl in the ascending limb into the interstitium
- Water flows by osmosis out of the descending limb, leaving a concentrated tubular fluid that flows to the ascending limb, where its NaCl will be pumped out into the interstitium
- Continous flow from the proximal tubule keeps a steady supply of hyperosmotic fluid in the thick ascending limb, where solutes are shuttled out of the tubules
- Repeated continuously so the process gradually traps solute in the interstititum and multiplies the its concentration
How does water reabsorption in the collecting ducts not ruin the medullary interstitial countercurrent exchange?
BECAUSE when ADH is present, it causes large amounts of water to be reabsorbed into the CORTEX. Small amounts of water are later absorbed in the medullary interstitium, but not much, and it’s quickly carried away by the vasa recta into venous blood
How does urea and its management contribute to urine concentrating ability?
-Urea is halfway reabsorbed at the proximal tubule
-Urea concentration rises in the tubular fluid along the nephron. UT-A2 helps at the thin LoH by passively secreting urea into the tubules.
-Thick LoH, distal tubules, and cortical collecting tubule are impermeable to urea
-At the medullary collecting ducts, urea concentration is at its highest, and is finally able to diffuse into the interstitium, as facilitated by urea transporters UT-A1 and UT-A3.
-Urea entering the interstitium can diffuse back into the thin LoH and “recycle”, keeping interstitial urea low and tubular urea high!!!
-ADH can activate UT-A3 and increase urea transport into the interstitium even more
-Water follows with the reabsorbed urea due to ADH influence, so the tubular fluid returns to a high concentration of urea
-about 50% of urea is urinated out
Briefly (2 points) how does renal medullary blood flow help keep solute concentration high?
- Medullary blood flow is low. It supplies the tissues as needed but minimizes solute loss from the “bespoke concentrated” interstitium
- The vasa recta act as countercurrent exchangers, which are U-shaped capillaries which become influenced by the concentrated medullary interstitial environment, but does not dissipate the hyperosmolarity
**Increased blood flow to the medulla reduces urine concentrating ability!
Briefly, how could large quantities of dilute urine be produced without increasing sodium excretion?
Decrease ADH secretion. This will reduce water reabsorption from urine to blood via its actions in the more distal tubules WITHOUT really altering Na+
Which two systems are most involved in regulating the concentration of Na and osmolarity of extracellular fluid?
- Osmoreceptor ADH system
- The thirst mechanism
Summarize the osmoreceptor ADH feedback system
- Increased plasma sodium causes osmoreceptor (special nerve cells) to shrink, and they fire
- Signal sent to supraoptic nuclei, then the posterior pituitary
- Post pit. releases ADH
- ADH in the blood finds kidneys, increases water permeability at the late distal tubules, cortical collection tubules, and medullary collecting ducts
- Increased water permeability = increased reabsorption and urine is now concentrated
Opposite occurs when plasma is hypo-osmotic and ADH is inhibited
From where is ADH synthesized and released, specifically?
- Magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus produce ADH.
-Released from the PPG. - Anteroventral region of the third ventricle (AV3V region) has osmoreceptors and at the subfornical organ and organum vasculosum, the vascular supplies lack the typical blood brain barrier so they’re extra sensitive to changes in blood ion levels
Describe the cardiovascular reflexes that respond to changes in blood volume or pressure and stimulate ADH release?
- Arterial baroreceptor reflexes
- Cardiopulmonary reflexes
At the aortic arch and carotid sinus (high pressure regions) and the cardiac atria (low pressure regions)
Vagus and glossopharyngeal nerves carry signals to the hypothalamic nuclei
Briefly list the stimuli that increase ADH secretion vs decrease it
Increases it:
Inc plasma osmolarity
Decr blood volume
Decr blood pressure
Nausea
Hypoxia
Morphine, nicotine, cyclophosphamide
Decreases it:
Decr plasma osmolarity
Inc blood volume
Inc blood pressure
Alcohol, clonidine
Briefly, what are the factors that stimulate vs inhibit thirst?
Thirsty if:
Inc blood osmolarity ***
Decr blood vol **
Decr blood pressure **
Inc angiotensin II **
Dry mouth
Not thirsty if:
Decr plasma osmolarity
Incr blood volume
Inc blood pressure
Decr angiotensin II
Gastric distension
Where is the “thirst center” in the brain? To what does it respond?
In the preoptic nucleus is the “thirst center” that responds to changes in osmolarity
increased osmolarity in the CSF at the third ventricle has the same response
What aspect of sodium and fluid amounts do angiotensin II and aldosterone influence?
They can change the amount of sodium in the ECF and increase the ECF volume but have almost NO effect on sodium concentration under normal conditions
Which system controls sodium concentration in the plasma?
The ADH-thirst system control osmolarity and plasma sodium concentration
What factors increase vs decrease cellular uptake of K+? (aka decrease extracellularly)
Shifts K into cells:
Insulin, Aldosterone, Beta-adrenergic stimulation , Alkalosis
Shifts K out of cells:
Insulin deficiency, aldosterone deficiency, Beta adrenergic blockade, Acidosis (reduces activity of the Na/K pumps), Cell lysis, strenous exercise, incr ECF osmolarity
The sum of which 3 factors determines renal K+ excretion?
- rate of K filtration
- rate of K reabsorption by the tubules
- Rate of K secretion by the tubules
Where is the most important site for regulating K+ excretion?
Where: The principal cells of the late distal tubules and cortical collecting tubules
Here, its secretion is regulated by activity of the Na/K ATPase, the EC gradient for K+ from blood to tubular lumen, and the permeability of the luminal membrane for K+
If the body needs to reabsorb K+, where does this occur and (briefly) how?
Where: intercalated cells
Via: H/K ATPase in the luminal membrane
What are the most important factors that stimulate K+ secretion by the principal cells?
What would decrease K+ secretion?
1) Increased ECF [K+]
2) Incr aldosterone
3) Incr tubular flow rate
Decreased by acidosis
How is K+ secretion INCREASED (when ECF K+ is high)?
- Incr activity of the Na/K ATPase
- The K+ conc gradient (higher now in renal interstitium) favors K+ flow into cells instead of backleaking
- Active secretion increases per stimulation by Aldosterone
How does Aldosterone stimulate K+ secretion?
Target: principal cells of the late distal tubule & collecting duct
Actions: Na/K ATPase pumps K out of cells into the tubules/pee; luminal membrane becomes more permeable to K+, enhancing secretion
How can high sodium intake challenge K+ homeostasis, and what mechanism keeps K+ conc regulated in this circumstance?
High Na+ = reduced aldosterone secretion, so K+ secretion decreases.
BUT high Na+ will increase tubular flow rate, which maintains a tubular environment of “low K+” that on its own increases K+ secretion
How does acute vs chronic acidosis each impact K+ secretion?
Acute acidosis inhibits the Na/K ATPase, thus decreasing intracellular K conc and thus diffusion into tubules. Net effect = keep more K+
Chronic acidosis inhibits proximal tubule NaCl and water reabsorption (voluminous pee), increasing distal volume delivery, which ‘washes away’/stimulates secretion of K+.
Net effect: K+ loss into urine
Why does alkalosis predispose patients toward hypocalcemic tetany?
Because in alkalosis, more Calcium is bound to plasma proteins!
In 3 brief points: How does PTH regulate plasma Calcium concentration?
- Stimulating bone resorption
- Stimulating activation of vitamin D to increase intestinal absorption
- Directly increasing renal tubular calcium reabsorption
How does Ca++ reabsorption change based on location in the nephron?
Proximal tubule: Independent of PTH here.
1. Diffuses down an EC gradient
2. Ca ATPase and Na counter-transport
Loop of henle: thick asc limb
Passive diffusion: + charge in lumen forces Ca into interstitium
PTH influenced: Transcellularly
Distal tubule:
PTH influenced: Ca ATPase active transport and Na counter transport
How does pH influence Ca++ dynamics?
Alkalosis stimulates Ca reabsorption
Acidosis inhibits Ca reabsorption
Summarize it: what factors increase calcium excretion (decrease plasma Ca)?
Low PTH
Increased ECF volume
Incr blood pressure
Decr plasma phosphate
Metabolic acidosis
Summarize it: what factors decrease calcium excretion (conserve plasma Ca)?
High PTH
Decr ECF
Decr blood pressure
Incr plasma phosphate
Metabolic alkalosis
Vit D3
Where in the nephron is phosphate reabsorbed, and what causes it to be reabsorbed vs excreted?
Where: Proximal tubule, and some at the distal tubule, by transcellular route
How: Usually all is absorbed unless the tubular max is reached, then its excreted.
How does PTH influence Phosphate dynamics?
Increased PTH dumps more phos into circulation from the bones –> high ECF phos
And PTH decreases the transport max, so more tubular phosphate is lost into the urine
How is magnesium excretion regulated?
*By changing tubular reabsorption
The primary site of reabsorption is the LoH, and a little in the distal/collecting tubules
Magnesium excretion increases when:
-ECF [Mg++] increases
-ECF volume expands
-ECF [Ca++] increases
Where is Mg++ stored in the body?
50% in the bones
About 50% in cells , and 1% in the ECF, and half of that in the plasma is bound to proteins
Briefly, what are the effects of the SNS on renal Na/H2O excretion?
-Pressure natiuresis and diuresis fall
-Na and H2O are conserved, such as with sudden hemorrhage, to raise plasma volume
Briefly, what are 4 major causes of fluid accumulation in the interstitial spaces?
- Incr capillary hydrostatic pressure
- Decr plasma colloid osmotic pressure
- Inc capillary permeability
- Lymphatic vessel obstruction
How does increased SNS tone to the kidneys conserve Na and H20?
- Constrict renal arterioles (may even dec GFR)
- Incr tubular salt and water reabsorbed
- Activate the RAAS, further saving salt and water to boost blood volume
*4. If volume drop is enough to trigger baroreceptors, SNS is EVEN MORE activated
Elevated Na has three main effects. What are they?
- Stimulate ANP release
- Inhibit the RAAS
- Pressure natiuresis
What is the role of atrial natriuretic peptide?
-Released from cardiac atrial muscle fibers
-Decreases renal sodium reabsorption by the collecting ducts
-Causes a small increase in GFR
Briefly, how do ACE inhibitor drugs work?
They shift the renal pressure-natriuresis curve to lower pressures so that more sodium and water will be excreted at lower BP values, and this chronically lowers BP
Valuable in congestive heart failure, when cardiac pumping ability is too weak to send the “increased pressure signal” to overcome the sodium-retaining effects of angiotensin II
What are the 4 main responses to elevated ECF sodium?
**the main trigger is the increased ecf volume caused by this Na increase
1. Activate low-pressure receptor reflexes: stretch receptors inhibit SNS output immediately and drop salt/water reabsorp. FIRST RESPONDER
2. Suppress angiotensin II formation to get rid of Na and drop aldosteroe
3. Stimulate natriuretic systems (ANP) to get rid of sodium
4. Small incr in arterial pressure –> incr pressure natriuresis
In short, why does cirrhosis and nephrotic syndrome lead to fluid retention?
Nephrotic syndrome: losing plasma proteins into urine reduces colloid osmotic pressure and leads to tissue edema and a fall in plasma volume
Cirrhosis: fibrotic liver doesn’t produce plasma protein and increases blood pressure by impeding portal flow, so develop edema from decr colloid pressure AND ascites from increased portal pressure
