Renal Lectures (8) Flashcards
Urine characteristics used in history as health indicators
L1
→ color (black - blackwater fever, too much Hb in pee)
→ clarity (froth: high protein)
→ odor (infection)
→ taste (diabetes - honey urine disease)
Primary Kidney Function
L1
→ homeostatic regulation of water and ion content in blood (fluid electrolyte balance)
Fluid-electrolyte balance is kept in kidneys how?
(secondary kidney functions)
L1
→ regulation of ECF volume (indirectly blood pressure) → osmolarity regulation → ion balance maintenance → pH homeostatic regulation → waste excretion → hormone production (like renin)
Can lose ___ kidney function before it affects homeostasis
L1
3/4
→ can have only 1/2 a kidney
Main structures in the urinary system
L1
→ ureter, urinary bladder, ureter, kidneys (2 concave structures, located retroperitoneally lying against peritoneal tissue layer)
→ adrenal glands on top kidney
→ Kidneys receive 20-25% of CO to ensure homeostasis maintained (issues fixed quickly)
Kidney structures
L1
→ outer region: cortex
→ inner portion: medulla (renal pyramids)
→ nephrons: make up bulk of kidneys, found in inner medulla
→ renal pelvis and ureter connects with nephrons so urine flows into them and into bladder
→ nephrons are functional unit of kidneys, ~1 million/kidney
→ 80% are cortical nephrons, 20% are juxtamedullary nephrons
Blood enters the kidneys via the _____, and then goes through ______.
L1
Blood enters the kidneys via renal artery → afferent arterioles → glomerulus (ball of capillaries) → efferent arterioles → peritubular capillaries → the renal vein
at glomerulus: where nephrons make contact with blood/solutes
*in juxtamedullary nephrons, peritubular capillaries is VASA RECTA
The glomerulus is the site of?
L1
filtration
→ blood enters the glomerulus and will filter into the bowman’s capsule, and if the fluid not reabsorbed, will be excreted
One nephron has 2 ____.
L1
2 arterioles and 2 sets of capillaries that form a portal system
Bowman’s Capsule
Parts of Nephron? Start at Bowman’s Capsule
L1
→ single layer of epithelial cells
→ where the glomerulus capillaries make contact with nephrons
*solutes and blood flows from capsule → proximal tubule → descending loop of Henle → ascending loop of Henle → distal tubule → collecting duct (ureter)
4 processes of kidneys?
L1
→ filtration (blood→lumen)
→ reabsorption (lumen→blood)
→ secretion (blood→lumen)
→ excretion (lumen→outside)
When/where do each of the kidney’s processes occur?
L1
→ Filtration: bulk flow of fluid/solutes in blood from glomerulus into bowman’s capsule lumen
→ Secretion: substances move from blood into lumen of any part of nephron via transporters
→ Reabsorption: In proximal tubule, some solutes/fluid moves from lumen back into blood (amnt depends on homeostasis needs)
→ Excretion: whatever is left in the nephron gets excreted out
Approximately ___ of plasma is filtered at the glomeruli/day
→ process of reabsorption in each structure of nephron
L1
180L
→ 99% reabsorbed, only ~1.5L is excreted
→ ~70% of reabsorption occurs at the proximal tubule via transporters. By end of proximal tubule, only ~55L is left that will go to loop of henle (30% of original vol)
→ loop of henle makes dilute urine: descending has water reabsorption so hyperosmotic. ascending has solutes reabsorbed, more than the amount of water reabsorbed (so dilute now) i.e. hypoosmotic. By end of loop, only 18L left (10%)
→ distal tubule and collecting duct finely regulate salt and water balance under hormone control (what does body need?)
→ 1.5L (0.8%) urine exits body, can be hyper or hypoosmotic, depends on body
Amount excreted =
L1
Amount filtered - amount reabsorbed + amount secreted
ex, 720mmol - 684mmol + 43mmol = 79mmol
→ these types of questions on exam can be 1 solute (like K+)
Filtration fraction
of all the plasma vol entering afferent arterioles, only 20% of that vol filters into bowman’s capsule. 80% continues on to the peritubular capillaries. In the proximal tubule of nephron, 19% is reabsorbed, so ,1% of vol is actually excreted. >99% enters kidneys and returns to systemic circulation
If someone’s cardiac output is 5L/minute, and the kidneys get ~20% of that, and ~60% of the blood is plasma, how much is entering the glomerulus everyday, if only 20% of the plasma filters into the bowman’s capsule?
THe number we find here is called?
L1
CO = 5L/min
Kidneys getting 1L/min
60% of 1L is 0.6L/min of plasma
20% of that plasma is filtered. thats 0.12L/min
0.12L/min x 60min/hour x 24 hours/day
= ~173L plasma filtered/day
round up to 180
this # is someone’s GLOMERULAR FILTRATION RATE (GFR) which can help to understand how well kidneys are functioning
Renal corpuscle: fluids and solutes passing into bowman’s from the glomerulus
L1
→ pass triple filtration barrier
- Capillary endothelial cells of glomerular capillaries → fenestrations (pores)
- Basal lamina surrounding glomerular capillary: mesangial cells can contract, and pull walls of capillaries together so there is less exposure to bowman’s and less filtration (reduces SA)
- Podocyte end-feet within renal corpuscle (surrounds glomerulus) act as barriers where substances have to fit in between the podocytes to enter lumen of bowman’s
Pressures governing filtration from glomerulus capillaries into renal tubules (bowman’s, etc)
L2
→ hydrostatic of glomerular capillaries, 55mm Hg: favours filtration! So over all bp drives filtration through 3 barriers and into capsule
→ colloid (oncotic) of blood, 30 mmHg: pressure gradient bc of plasma proteins in capillaries, draws fluid back into capillaries, opposes filtration (favours reabsorption)!
→ hydrostatic of bowman’s, 15 mmHg: fluid already in the nephron opposes filtration
Net filtration pressure 10 mmHg
→ not a lot, but pores let fluid go through and theres ~2 million nephrons so tons occuring
GFR basics
Factors affecting GFR?
L2
→ vol of fluid filtered from glomerulus into bowman’s per unit time
→ normally 125ml/min or 180L/day
→ plasma vol is ~3L so kidneys filter all plasma vol ~60x /day
→ If not reabsorbed, we’d run out of plasma in ~24 minutes
FACTORS
→ filtration pressure
→ filtration coefficient (slit surface area and permeability)
Why is GFR relatively constant throughout range of bp?
What if afferent arteriole resistance increases?
L2
→ many structures controlling amnt of blood flowing into glomerulus and nephron to prevent damage: renal arterioles, afferent and efferent alter their constriction
→ afferent arteriole: can constrict (inc resistance) to reduce blood flowing into the glomerulus, as well as capillary bp and thus GFR
Renal blood flow depends on ____.
What if resistance in efferent arteriole is inc?
Afferent resistance dec (dilates)?
L2
Overall resistance: resistance in afferent + efferent arterioles
→ inc resistance in efferent arterioles to reduce overall flow in response to high bp: filtration will increase since afferent letting in same amount, but less leaving. Pooling will occur in glomerulus. inc hydrostatic pressure, inc GFR
→ dec resistance in afferent: blood flow increases since afferent letting more in, but since same amount leaving, blood will pool in glomerulus. Hydrostatic pressure inc, GFR inc.
What type of regulation of renal blood flow is most common?
Common themes: when does GFR and RBF dec/inc?
L2
Constricting afferent arteriole in response to inc bp
→ RBF and GFR not always proportional: GFR can inc when RBF dec, or they can both inc/dec etc
→ any dilation will increase RBF, any constriction will dec it
→ pooling will inc hydrostatic pressure and GFR (i.e. dilating afferent or constricting efferent)
→ dilating efferent or constricting afferent dec GFR bc less blood in there so less hydrostatic pressure
How does GFR autoregulate?
L2
*protects filtration barriers from high bp (and high GFR) that would damage them (hypertension)
→ myogenic response of afferent arterioles: as bp goes up, blood flow inc coming into afferent arterioles, blood stretches smooth muscle in walls, will reflectively constrict
→ tubuloglomerular feedback: juxtaglomerular apparatus (nephron loops back on itself so ascending Henle passes b/n arterioles) has macula densa cells that sense inc in distal tubule blood flow and release paracrines to affect arteriolar diameter
How does stretch activate myogenic activity of afferent arterioles?
L2
→ stretch membranes open → let Na or Ca in → vascular smooth muscle depolarizes → L type Ca channels open → inc in intracellular Ca turns on myosin light chain kinase → leads to constriction
Granular cells
L2
→ kind of sit outside afferent and efferent arterioles
→ secrete renin: enzyme involved in salt and water balance
How do macula densa cells sense the inc in fluid and solutes passing them (i.e. the inc in GFR)?
L2
→ more filtration = more NaCl picked up, as they start to pick up more, probably inc ATP conversion into adenosine (paracrine signal)
→ also have cilia which could sense that the cilia are moving more as flow inc and inc ATP conversion to adensosine
Sympathetic neurons affecting GFR: integrating centers outside kidneys
L2
→ can override the local control mechanisms (arteriole resistance) by altering resistance
→ neurons release norepinephrine to act on a1 adrenergic receptors of both afferent and efferent arterioles and cause vasoconstriction to reduce GFR
→ only intervene when large rapid drop in bp and water needs to be conserved - keep as much fluid in blood as possible(hemorrhage, severe dehydration)
Hormones influencing GFR: integrating centers outside the kidneys
L2
→ angiotensin || (potent vasoconstrictor)
→ prostaglandins (vasodilators)
Believed to alter filtration coefficient by acting on podocytes (affect permeability) or mesangial cells (affect SA)
→ A || causes filament contraction so capillaries are pulled together and swells podocytes (less glomerular filtration)
→ prostaglandins do opposite
Regulated reabsorption allows kidneys to ____.
Why do we filter 180 L if only 1% is excreted?
L2
→ selectively return ions and water to plasma to maintain homeostasis
→ we still filter 180 L since its a rapid way to remove unwanted materials since the nephron is technically “outside the body”
→ frequent filtration of ions and water simplifies regulation and helps to adapt and maintain homeostasis within narrow range
Reabsorption is active and passive at the proximal tubule
L2
from lumen → apical memb → basolateral memb → ECF
***this accounts for 70% of reabsorption
→ Na reabsorption is active (creates gradient for rest of steps)
→ electrochemical gradient drives anion reabsorption
→ water moves by osmosis following solute reabsorption
→ permeable solutes (K, Ca, urea) diffuse.
anions, water, and permeable solutes can move both paracellularly or transepithelially (transcellular). Na can only move transcellularly.
Active transport of Na in the proximal tubule (reabsorption)
L3
Basolateral Na-K ATPase
→ Epithelial Na channel sits on apical membrane, lets Na inside proximal tubule cell (follows concentration gradient)
→Na pump sits on basolateral memb and immediately pushes Na out so [Na] stays low inside tubule cell for diffusion across apical
Secondary active transport: Glucose symport with Na
→ Same as above; Na comes across apical following its concen gradient, glu tags along via SGLT protein
→ glu diffuses out of basolateral memb via GLUT protein
→ Na pumped out via ATPase (same as above)
Proximal tubule (reabsorption):
Passive reabsorption of Urea
Endocytosis of plasma proteins
L3
→ after Na, Cl and H2O movement, [urea] in tubule inc since less fluid, and is low in ECF, so it can now diffuse across tight junctions
→ receptor (megalin) binds plasma proteins or peptides from tubule lumen, causes receptor mediated endoycotis and brings solute into cell, fuses with lysosome, protein broken down into AA, AA’s then reabsorbed
Saturation of renal transport (reabsorption)
L3
Since most subs use memb proteins for transport, max rate of transport occurs when all carriers/transporters used → some solute remains in tubule
ex, Glucose
at [plasma glucose] of 300 mg/100 ml plasma, reabsorption levels off (more glucose filtered then is reabsorbed - some gets excreted *diabetes)
i.e. transport max = 375 mg/ml
Renal Threshold
L3
→ [plasma solute] when it first starts to appear in urine (transport maximum)
→ excretion = filtration - reabsorption (filtration will be larger)
→ genetic disorders can have reduced transporters so threshold is lower for glucose (glycosuria/glucosuria)
Peritubular capillary pressures favour reabsorption
L3
→ water/solutes initially reabsorbed from tubule (lumen) into Interstitial space and must re-enter circulation via pressure gradients
→ since oncotic pressure is 30, and hydrostatic is only 10, net reabsorption of 20 mmHg drives fluid/solutes from ICF into capillaries (bulk flow)
Secretion
L3
→ ECF to lumen of nephron
→ depends mainly on memb transport proteins
→ active, regulated, process
→ needs to occur so homeostatic regulation of K+ and H+ and organic compounds occurs (medications)
→ also needed to enhance excretion of a substance (medications)
- excreted = filtered - reabsorbed + secreted
Secretion of Xenobiotics
L3
foreign substances
→ TERTIARY active transport process
1. Direct: Na transport to create low [Na] inside tubule cell
2. Indirect: Na-dicarboxylate cotransporter (NaDC) uses [na] gradient to inc [dicarboxylate] inside tubule
3. Indirect: basolateral organic anion transporters (OAT1-3) uses [dicarboxylate] going down its gradient (across baso) to bring in organic ions into cell
→ organic anions then enter lumen by OAT4 in exchange for dicarboxylate
How carbon cased ions moved
Penicillin excretion and competitor
L3
→ almost all penicillin ingested is excreted within 3-4 hours by tertiary active transport process
→ penicillin then given with probenecid (its competitor) which has higher affinity for OAT (secreted first!)
Excretion and renal clearance
L3
→ whatever’s left after filtration, reabsorption and secretion
→ can’t tell us much about kidney function
Renal handling of substance (what’s handled and cleared by kidneys) and GFR of interest, as GFR is indicator of overall kidney health, and renal handling/clearance gives information as to how/what kidneys remove from body (drug clinical trials!)
Measuring Clearance
L3
→ rate that solute is removed from body (excretion or metabolism)
→ measure GFR non-invasively
Clearance of X = excretion rate of X (mg/min) / [X in plasma] (mg/ml plasma)
*excretion rate = how much is found in urine
→ i.e. volume of plasma passing through kidneys that’s been totally cleared of the solute in given period of time
(looks at blood cleared of solute, not excreted)
Urea clearance is 65 = kidney removes all urea in 65ml of plasma in 1 minute
To accurately determine GFR look at clearance of substance that is ____.
L3
Freely filtered, and neither reabsorbed or secreted
i.e. if everything is excreted, clearance = GFR
→ INULIN is most accurate way! All of it is excreted, but impractical because its not found in our body
If clearance of inulin = 100ml/min
so GFR = 100ml/min
If inulin is impractical, how if GFR measured via clearance?
L4
→ CREATININE: freely filtered, but slightly secreted
→ naturally occuring in body
→ creatinine clearance slightly overestimates GFR but its close
So if clearance of creatinine is 125ml/min, GFR will be slightly <125ml/min
Ex Question
if plasma creatinine is 1.8mg/100ml of plasma, urine creatinine is 1.5mg/ml urine and the urine volume, in 24 hours, is 1100ml, what is the creatinine clearance? What is GFR?
L4
clearance = 63.9ml/min
GFR slightly lower
Determining net renal handling: filtered load =
→ net reabsorption or secretion
L4
use filtered load to find how kidneys handle solute
Filtered load = [X in plasma] x GFR
*compare filtered load with excretion rate:
→ excretion < filtered = net reabsorption (not all cleared)
→ excretion > filtered = net secretion
→ excretion = filtered, substance freely filtered/secreted eg. inulin
*also compare GFR to the clearance of solute to tell
→ clearance < GFR = net reabsorption
e.g. glucose which is 100% reabsorbed or urea which is 50% since GFR is 2x as big as clearance value
If excretion is > filtration rate, what has occured?
L4
Net secretion
ex. Penicillin, artificial sweeteners
(or, clearance > GFR)
Micturition reflex activated by?
Path of fluid kidneys → bladder
What helps move the fluid?
L4
stretch receptors being activated by the bladder filling
→ fluid enters kidneys, nephrons empty into major and minor calyces. Fluid moves minor to major, where major enters into renal pelvis, then ureter, then empties into bladder for removal
→ to push fluid into bladder needs help of gravity and rhythmic contractions of smooth muscle in ureter (like pacemaker)
How does the bladder stretch activate the micturition reflex?
L4
→ stretching of bladder due to vol inc sends info to spinal cord causing contraction of detrusor muscles (smooth muscle in bladder walls) to reflexively contract
→ this reflexive pulse causes opening of internal urethral sphincter
→ also sends info up to cerebral cortex to relax/open external urethral sphincter
→ if you can’t pee at that moment, the parasympathetic activity is inhibited so reflex “stops”: descending input from cortex inhibit parasympathetic input so reflex does not occur and external sphincter remains contracted
Sphincters
L4
→ internal urethral sphincter: smooth muscle at urethra/bladder junction: when micturition occurs and fluid pressure increases on it, passively opens. Can consciously keep it contracted to inhibit peeing
→ external: skeletal muscle, what we can consciously ‘clench’ (contract, kegels) to inhibit urination
Urge to pee appears when?
When can you no longer hold pee?
L4
200ml urine in bladder
→ >500ml internal sphincter forced open, leads to reflexive opening of internal and external sphincter and loss of l=voluntary opposition
→ still have 10ml left over in bladder afterward!
Incontinence
L4
→ inability to control urination voluntarily
→ in babies, corticospinal connections not yet made to stop reflex from occurring
as adults
→ can have internal/external sphincter damage (childbirth)
→ spinal cord damage
→ aging (lost of muscle tone)
→ prostate growth in males
→ stroke, alzheimer’s, other CNS diseases affecting cerebral cortex or hypothalamus
Fluid/electrolyte balance: 4 parameters to maintain
L5
→ fluid volume
→ osmolarity
→ concentrations of individual ions (Na, K, Ca)
→ pH
How is excess solute/fluid excreted?
L5
→ kidney’s (primary, urine is regulated mechanism)
→ feces, sweat (small amount unless excessive or diarrhea)
→ lungs (water, H+, HCO3-)
Which solutes are we concerned about homeostasis?
L5
→ H2O, Na determine ECF vol and osmolarity
→ K+ has cardiac and muscle functions (hypokalemia and hyperkalemia)
→ Ca+ (bones)
→ H+, HCO3- (pH)
How can some cells keep cell vol normal (ECF)?
L5
→ renal tubule cells in loop of Henle in juxtamedullary nephrons constantly exposed to hypertonic ECF and adjust osmolarity to it by producing organic solutes (sugar, alcohols, AA’s) to match their ICF osmolarity to ECF
→ some cells use vol change to initiate responses: liver cells begin protein and glycogen synthesis in response to swelling
Systems helping to regulate fluid/electrolyte balance
L5
→ respiratory system *neural control, rapid response
→ cardiovascular system *neural control, rapid response
→ renal system *under (neuro)endocrine control and since hormone release takes time, these responses take days
→ behavioral (thirst/salt craving)
An increase in blood volume and pressure causes?
L5
→ volume receptors in atria, endocrine cells in artia, and carotid/aortic baroreceptors pick it up and trigger….
→ cardiovasc reflex: decreases CO and causes vasodilation
→ kidney: excrete salt/water in urine (dec ECF and ICF vol)
reduces bp
Pathways overlap
volume receptors: low pressure baroreceptors, respond to inc atrial filling during rest causing inc blood vol/pressure
A decrease in blood volume and pressure causes?
L5
→ volume receptors in atria and carotid/aortic baroreceptors pick it up and trigger….
→ cardiovasc reflex: inc CO and cause vasoconstriction
→ kidneys conserve salt/water to minimize more vol loss
→ behavioural: inc thirst causes inc water uptake (ECF and ICF vol increase)
Water balance
L5
→50-60% body weight is water
→ standard man, total fluid is 42L, where 28L (2/3) of that is ICF, and 14L (1/3) is ECF
of the 14L in ECF, 25% is plasma and 75% is interstitial fluid
Kidneys conserving water
L5
think of body as a coffee cup where the kidneys are the handle
→ vol gain causes less reabsorption, more excretion (pee more)
→ vol loss (drop in GFR) causes more absorption, less excretion
→ vol loss must be replaced via behavioural mechanisms since kidneys can only modify what’s in the body already
Renal Medulla creates ___.
L5
Concentrated urine
→ when removal of excess water needed, kidneys make large vol of dilute urine (osmolarity can be 50 mOsM)
→ excess urine removal=diuresis
→ to make dilute urine, distal nephron reabsorbs solute without allowing water to follow (close aquaporins)
→ to conserve water, kidneys make low vol of very concentrated urine (osmolarity can be 1200 mOsM)
→ to make concentrated urine, distal nephron reabsorbs water and little solute (interstitial space is very hyperosmotic all the time just in case more H2O needs to be reabsorbed)
Creation of Concentrated urine
L5
→ reabsorption at proximal tubule is isosmotic
in the loop of henle:
→ descending only permeable to water, solutes keep going (because interstitial pace very hyperosmotic). At end of descending, have hyperosmotic filtrate (1200 mOsM)
→ ascending only permeable to solutes, absorbs way more filtrate than fluid was absorbed in descending. At end of ascending, hypoosmotic filtrate
→ at distal tubule, based on hormone control, permeability to water or solutes changes and can create concentrated/dilute urine
Vasopressin (AVP)
L5
→ controls addition/removal of aquaporins on apical memb of tubule cells in distal tubule and collecting duct
→ less hormone: removal, H2O stays in nephron and exits body (hypoosmotic urine)
→ more hormone: addition, H2O is reabsorbed into interstitial fluid (concentrated/hyperosmotic urine leaves)
→ posterior pituitary hormone, antidiuretic made in hypothalamus
→acts on V2 receptor to phosphorylate proteins on vesicles storing A2 channels, causes exocytosis and insertion of A2’s across apical membrane
→ INSERTION IS ALL OR NONE, DEPENDS ON [VASOPRESSIN] IN BLOOD
What stimuli controls vasopressin secretion?
L5
activates:
→ mainly, HIGH osmolarity: >260 mOsM potent stimuli
→ dec arterial stretch due to low blood vol
→ dec bp
inhibits:
→ inc baroreceptor input (high bp and vol)
→ ANP
all of these sensed and sent to hypothalamus where AVP is synthesized in response
*shows circadian rhythm
Magnocellular neurosecretory cells (MNC’s)
L6
→ make AVP in cell body, exocyte at terminal
→ stored in posterior pituitary
→ change activity based on osmolarity
→ osmoreceptor neurons stretch with inc fluid. So when osmolarity increases (hypertonic solution) they shrink and inc firing rate. When they start stretching, inactivate
→ then signal to MNC’s to let Ca in; ICF fluid leaves, cell depolarizes, AP causes release of vesicles containing AVP
→ always active to some degree
→ hypotonic environment is opposite (less AVP released)
*baroreceptors and atrial receptors signal to MNC’s too
What creates hyperosmotic interstitium and keeps it like that?
L6
→ countercurrent exchange system: venous and arterial blood pass each other (i.e. ascending and descending loops are CLOSE to each other)
→ urea makes up 50% solute in interstitium: distal nephron creates recycling loop: 50% filterted urea goes through loop, then secreted back into loop and continues
Renal countercurrent exchange system
L6
→ loop of henle (countercurrent multiplier) and peritubular capillaries (vasa recta) flow opposite ways
→ function together to maintain hyperosmotic interstitium: filtrate entering descending becomes more concentrated as it loses water, and the blood in vasa recta removes water leaving Henle. Ascending pumps out solutes and becomes hyposmotic.
→ vasa recta is picking up more water than solute, interstitium becomes hyperosmotic (water secreted from descending is minimal anyway so it wouldn’t dilute interstitium much but still picked up)
*nephrons
Active transport in the loop of Henle
L6
Reabsorption of Na and K – 25% occurs in ascending limb
→ NKCC transporter on apical membrane uses energy from Na concentration gradient (ATPase) to move K+ and 2 Cl- into ascending cells
→ NKCC is target for diuretic drugs during hypertension and edema treatments (dec water reabsorption)
How does the vasa recta remove water?
L6
→ as it is going opposite direction, picks up solute first, blood becomes hyperosmotic, so water in interstitium has gradient as the blood passes descending area
What’s the main job of the countercurrent multiplier? Exchanger?
L6
→ multiplier: create hypertonic interstitium
→ exchanger: prevent dilution of hypertonic interstitium via picking up water leaving descending
If we ingested 9g of NaCl what would happen (this is daily av of an American diet)
L6
→ that’s 155mOsM of Na and Cl
→ if we ingested that much, since our normal [Na] in plasma is ~140mOsM/L, we’d have to drink 1.4L of water!!! Big inc in bp
→ if we didn’t drink any water, our body osmolarity would increase from 300 to 307mOsM (lots) – they’d shrink and disrupt normal cell function
How do we maintain mass balance (in response to salt ingestion)?
L6
→ no vol change, but osmolarity inc
→ secrete vasopressin to inc renal water reabsorption which inc ECF volume and BP (conserve H2O)
→ behavioural: thirst occurs, inc water intake (returns osmolarity) but ECF vol and BP inc
→ due to vol inc, kidneys excrete sale/H2O (slow response) to return osmolarity, bp and vol to normal
→ due to bp intake, cardiovasc reflexes lower bp (CO dec) rapidly to return bp and vol
Aldosterone helps to __.
L6
Control Na balance
→ renin-angiotensin-aldosterone system
→ aldosterone is steroid hormone that inc Na reabsorption and K excretion via acting on principle cells
→ targets last 3rd of distal tubule and portion of collecting duct found in cortex of kidney
Aldosterone acting on principle cells
L7
In early response phase:
→ aldosterone binding its receptor inside P cell of distal nephron stimulates apical Na-K channels to open (flicker close less often)
→ principal cells change reabsorption/secretion of Na-K: inc Na entry into cell so basolateral Na-K pump goes quicker: inc Na reabsorption and K secretion
→ apical membrane channel: ENaC (epithelial Na channels) and ROMK (renal outer medulla K channels)
In late response phase:
→ hormone ligand complex translocate into cell nucleus, binds to hormone response elements to inc transcription of Na channels, basolateral Na-K pumps (and maybe apical K channels)
→ new channels form
→ further inc in Na reabsorption and K secretion
→ long time to activate
What drives/inhibits aldosterone secretion?
L7
→ excess K: acts on adrenal cortex to protect body from hyperkalemia (inc excretion)
→ ~dec bp: initiate RAS pathway (secretes angiotensin || which triggers aldosterone). Dec bp can also inc Na reabsorption to inc reabsorption instead tho
→ large dec in plasma Na can stimulate aldosterone section hyponatremia
→ inc osmolarity (hyperosmotic) acts on adrenal cortex during dehydration to inhibit aldosterone release (want less reabsorption since already hyper)
→ ANP inhibits it: high fluid levels in body
Renin-antgiotensin-system (RAS)
L7
→ multistep pathway for bp regulation
→ helps baro reflex to fix low bp (low vol)
→ influences CVCC
dec bp (less stretch on afferent arteriole walls) causes …
1. GFR dec causes paracrine release from macula densa cells (less filtration, signal to release renin)
2. CVCC inc sympathetic activity: baroreceptor reflex (inc vasoconstriction, signal renin secretion)
3. granular (juxtaglomerular) cells secrete renin: **cleave angiotensinogen in plasma into angiotensin 1. From there, ACE enzyme (in blood vessel epithelium) cleaves angiotensin 1 into angiotensin 2
Angiotensin 2 signals what what?
L7
→ arterioles: vasoconstriction
→ CVCC: inc sympathetic response (inc CO)
→ hypothalamus (pituitary gland): inc vasopressin and thirst (inc volume)
→ adrenal cortex: inc aldosterone (inc Na reabsorption)
→ proximal tubule: inc Na reabsorption (stimulates apical Na-H exchanger)
POTENT VASOCONSTRICTOR
All these function to bring up blood pressure. Some inc vol while maintaining osmolarity
Hypertension treatment with ANG||
L7
→ use ACE inhibitors (since ACE causes ANG|| activation to bring bp up) will relax vasculature
Atrial natriuretic peptide (ANP)
L7
→ promotes Na and H2O excretion (opposite of aldosterone/vasopressin)
→ acts in opposition of RAS, brings bp down
→ peptide hormone made and secreted by specialized myocardial cells in atria of heart
*stimulus: inc blood vol
→ causes inc stretch of atria causing these cells to release ANP
→ ventricles/brain neurons make BNP
ANP affects:
L7
→ kidney’s (relaxes afferent arterioles and inc GFR, reduce renin release from granular cells, reduce Na reabsorption at collecting duct)
→ hypothalamus (reduce AVP release)
→ adrenal cortex (inhibit aldosterone release)
→ Medulla (CVCC; dec sympathetic output i.e. dec bp)
Potassium Balance
L7
→ K passively reabsorbed in proximal tubule, some in ascending limb
→ plasma [K] ~3.5-5mmol
→ secreted at distal tubule and cortical collecting duct
→ aldosterone controls reabsorption/secretion
→ normal [K] excretion is 10-20%. low levels of aldosterone i.e. small amnt of secretion
→ low [K] dec aldosterone release, reducing secretion. Excretion is 2% *hypokalemia
→ high [K] inc aldosterone release, increases secretion. Excretion ~10-15% *initial hyperkalemia, then hypokalemia
Why is potassium balance important? Hyper and hypokalemia? Issues with them? Causes of K balance disturbances? L7
→ alterations affect resting memb potential (affects APs)
→ hyperkalemia: more K in fluid, less leaking OUT of cell so cell is depolarized (more excitable)
→ hypokalemia: low K in cell so more leaking OUT of cell so cell is hyperpolarized (less excitable)
→ this is really important in heart or skeletal muscle tissue!
→ Hypokalemia causes muscle weakness
→ hyperkalemia can lead to life threatening arrhythmias in heart
K disturbances can result from kidney dysfunction, eating disorders, loss of K in diarrhea or use of diuretics prevent kidneys from properly reabsorbing K
Behavioural responses for salt and water balance
L8
→ important in restoring normal state especially when ECF volume dec or osmolarity deviates
→ in hyperosmotic state, drinking water is only way to replace lost water
→ in hypoosmotic state, eating salt is only way to inc Na content
Areas in hypothalamus act as osmoreceptors (drive thirst)
→ when drinking, thirst is relieved immediately, not when water is absorbed due to unknown receptors in mouth and pharynx: feedward mechanism – reduce AVP release
→ why thirst comes in waves
→ prevents osmolarity swing
Thirst stimulus and process
L8
→ inc osmolarity, dec flow of saliva, dec blood volume
→ Saliva stimulates thirst centre in hypothalamus
→ Osmolarity stimulates osmoreceptors in hypothalamus, then thirst centre
→ dec blood volume = dec bp which inc renin release (and angiotensin || formation), dec baroreceptor activation which stimulate thirst centre in hypo
What physiological changes influence inc Na appetite?
L8
→ inc aldosterone
→ inc angiotensin
→ changes in [Na] in brain
Avoidance behaviours
L8
help prevent dehydration
ex, desert animals avoid heat of day and move at night (nocturnal)
ex, midday siesta in hot places
Osmolarity and blood volume change independently resulting in 8 different senarios
L8
1 →inc vol and inc osmolarity (like eating lots of salty foods and a little water) – ingestion of hypertonic saline (salt > water) – excrete hypertonic urine
2 →inc vol, no osmolarity change (if eating same amount of salt as drinking water) – ingestion of isotonic saline – isotonic urine
3 → inc vol, dec osmolarity (drinking pure water) – hypotonic urine (however can’t excrete pure water, some solute lost, imperfect compensation) w salt appetite
4 →no vol change, inc osmolarity (eating salt) – hypertonic urine (concentrated), intense thirst
5 →no vol change, dec osmolarity (like sweating, then only drinking water to replenish vol) – can cause hypokalemia/hyponatremia since lost solutes not replaces *gatorade
6 → dec vol, inc osmolarity (heavy exercise or diarrhea) – can cause inadequate perfusion and cell dysfunction and possible for brain to not get enough blood – drink water
7 → dec vol, no change in osmolarity (hemorrhage) – need blood transfusion or ingestion/Iv of isotonic solution
8 → dec vol, dec osmolarity (uncommon, but can result from incomplete dehydration compensation)
Responses to changes in vol and osmolarity (4)
L8
→ dec in bp/vol: carotid and aortic baroreceptors and atrial vol receptors cause thirst stimulation and vasopressin secretion, as well as granular cells secrete renin (RAS) and glomerulus dec GFR
→ inc bp: carotid and aortic baroreceptors and atrial vol receptors cause thirst and vasopressin inhibition, as well as myocardial cells secrete natriuretic peptide and glomerulus inc GFR
→ inc osmolarity: osmoreceptors stimulate thirst and secrete vasopressin, as well as adrenal cortex dec aldosterone secretion
→ dec osmolarity: osmoreceptors dec vasopressin secretion, as well as adrenal cortex inc aldosterone secretion
Severe dehydration responses
L8
i.e. ECF vol loss, bp dec, osmolarity inc
→ conserving fluids
→ cardiovasc reflexes inc bp
→ thirst stimulated
4 compensatory mechanisms to dehydration are:
L8
*vol loss, bp dec, osmolar. inc
(overlap!)
→ cardiovasc mechanisms (carotid and aortic baro’s signal CVCC to inc CO, arterioles vasoconstrict, also sympathetic output stimulates granular cells)
→ RAS (granular’s secrete renin…)
→ renal mechanisms (dec GFR is felt by macula densa cells, stimulates granular cells)
→ hypothalamic mechanisms (artial vo, osmoreceptors, and carotid/aortic baro’s send info to hypothalamus to inc vasopressin and stimulate thirst)
“during severe dehydration decreased ECF volume would signal the RAS to release AngII and increase aldosterone release, but at the same time an increased osmolarity inhibits aldosterone release”
What would happen?
L8
Osmolarity reigns and aldosterone is not secreted
→ if it was, Na would be reabsorbed which would worsen the already high osmolarity
