Renal Lectures (8)

Question 1

Urine characteristics used in history as health indicators

L1

Answer 1

→ color (black - blackwater fever, too much Hb in pee)
→ clarity (froth: high protein)
→ odor (infection)
→ taste (diabetes - honey urine disease)

Question 2

Primary Kidney Function

L1

Answer 2

→ homeostatic regulation of water and ion content in blood (fluid electrolyte balance)

Question 3

Fluid-electrolyte balance is kept in kidneys how?
(secondary kidney functions)
L1

Answer 3

→ regulation of ECF volume (indirectly blood pressure)
→ osmolarity regulation
→ ion balance maintenance
→ pH homeostatic regulation
→ waste excretion
→ hormone production (like renin)

Question 4

Can lose ___ kidney function before it affects homeostasis

L1

Answer 4

3/4

→ can have only 1/2 a kidney

Question 5

Main structures in the urinary system

L1

Answer 5

→ 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)

Question 6

Kidney structures

L1

Answer 6

→ 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

Question 7

Blood enters the kidneys via the _____, and then goes through ______.
L1

Answer 7

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

Question 8

The glomerulus is the site of?

L1

Answer 8

filtration
→ blood enters the glomerulus and will filter into the bowman’s capsule, and if the fluid not reabsorbed, will be excreted

Question 9

One nephron has 2 ____.

L1

Answer 9

2 arterioles and 2 sets of capillaries that form a portal system

Question 10

Bowman’s Capsule
Parts of Nephron? Start at Bowman’s Capsule
L1

Answer 10

→ 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)

Question 11

4 processes of kidneys?

L1

Answer 11

→ filtration (blood→lumen)
→ reabsorption (lumen→blood)
→ secretion (blood→lumen)
→ excretion (lumen→outside)

Question 12

When/where do each of the kidney’s processes occur?

L1

Answer 12

→ 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

Question 13

Approximately ___ of plasma is filtered at the glomeruli/day
→ process of reabsorption in each structure of nephron
L1

Answer 13

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

Question 14

Amount excreted =

L1

Answer 14

Amount filtered - amount reabsorbed + amount secreted

ex, 720mmol - 684mmol + 43mmol = 79mmol

→ these types of questions on exam can be 1 solute (like K+)

Question 15

Filtration fraction

Answer 15

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

Question 16

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

Answer 16

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

Question 17

Renal corpuscle: fluids and solutes passing into bowman’s from the glomerulus
L1

Answer 17

→ pass triple filtration barrier

1. Capillary endothelial cells of glomerular capillaries → fenestrations (pores)
2. 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)
3. 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

Question 18

Pressures governing filtration from glomerulus capillaries into renal tubules (bowman’s, etc)
L2

Answer 18

→ 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

Question 19

GFR basics
Factors affecting GFR?
L2

Answer 19

→ 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)

Question 20

Why is GFR relatively constant throughout range of bp?
What if afferent arteriole resistance increases?
L2

Answer 20

→ 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

Question 21

Renal blood flow depends on ____.
What if resistance in efferent arteriole is inc?
Afferent resistance dec (dilates)?
L2

Answer 21

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.

Question 22

What type of regulation of renal blood flow is most common?
Common themes: when does GFR and RBF dec/inc?
L2

Answer 22

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

Question 23

How does GFR autoregulate?

L2

Answer 23

*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

Question 24

How does stretch activate myogenic activity of afferent arterioles?
L2

Answer 24

→ 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

Question 25

Granular cells

L2

Answer 25

→ kind of sit outside afferent and efferent arterioles

→ secrete renin: enzyme involved in salt and water balance

Question 26

How do macula densa cells sense the inc in fluid and solutes passing them (i.e. the inc in GFR)?
L2

Answer 26

→ 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

Question 27

Sympathetic neurons affecting GFR: integrating centers outside kidneys
L2

Answer 27

→ 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)

Question 28

Hormones influencing GFR: integrating centers outside the kidneys
L2

Answer 28

→ 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

Question 29

Regulated reabsorption allows kidneys to ____.
Why do we filter 180 L if only 1% is excreted?
L2

Answer 29

→ 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

Question 30

Reabsorption is active and passive at the proximal tubule

L2

Answer 30

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.

Question 31

Active transport of Na in the proximal tubule (reabsorption)

L3

Answer 31

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)

Question 32

Proximal tubule (reabsorption):
Passive reabsorption of Urea
Endocytosis of plasma proteins
L3

Answer 32

→ 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

Question 33

Saturation of renal transport (reabsorption)

L3

Answer 33

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

Question 34

Renal Threshold

L3

Answer 34

→ [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)

Question 35

Peritubular capillary pressures favour reabsorption

L3

Answer 35

→ 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)

Question 36

Secretion

L3

Answer 36

→ 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

Question 37

Secretion of Xenobiotics

L3

Answer 37

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

Question 38

Penicillin excretion and competitor

L3

Answer 38

→ 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!)

Question 39

Excretion and renal clearance

L3

Answer 39

→ 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!)

Question 40

Measuring Clearance

L3

Answer 40

→ 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

Question 41

To accurately determine GFR look at clearance of substance that is ____.
L3

Answer 41

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

Question 42

If inulin is impractical, how if GFR measured via clearance?

L4

Answer 42

→ 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

Question 43

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

Answer 43

clearance = 63.9ml/min

GFR slightly lower

Question 44

Determining net renal handling: filtered load =
→ net reabsorption or secretion
L4

Answer 44

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

Question 45

If excretion is > filtration rate, what has occured?

L4

Answer 45

Net secretion
ex. Penicillin, artificial sweeteners
(or, clearance > GFR)

Question 46

Micturition reflex activated by?
Path of fluid kidneys → bladder
What helps move the fluid?
L4

Answer 46

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)

Question 47

How does the bladder stretch activate the micturition reflex?
L4

Answer 47

→ 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

Question 48

Sphincters

L4

Answer 48

→ 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

Question 49

Urge to pee appears when?
When can you no longer hold pee?
L4

Answer 49

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!

Question 50

Incontinence

L4

Answer 50

→ 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

Question 51

Fluid/electrolyte balance: 4 parameters to maintain

L5

Answer 51

→ fluid volume
→ osmolarity
→ concentrations of individual ions (Na, K, Ca)
→ pH

Question 52

How is excess solute/fluid excreted?

L5

Answer 52

→ kidney’s (primary, urine is regulated mechanism)
→ feces, sweat (small amount unless excessive or diarrhea)
→ lungs (water, H+, HCO3-)

Question 53

Which solutes are we concerned about homeostasis?

L5

Answer 53

→ H2O, Na determine ECF vol and osmolarity
→ K+ has cardiac and muscle functions (hypokalemia and hyperkalemia)
→ Ca+ (bones)
→ H+, HCO3- (pH)

Question 54

How can some cells keep cell vol normal (ECF)?

L5

Answer 54

→ 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

Question 55

Systems helping to regulate fluid/electrolyte balance

L5

Answer 55

→ 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)

Question 56

An increase in blood volume and pressure causes?

L5

Answer 56

→ 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

Question 57

A decrease in blood volume and pressure causes?

L5

Answer 57

→ 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)

Question 58

Water balance

L5

Answer 58

→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

Question 59

Kidneys conserving water

L5

Answer 59

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

Question 60

Renal Medulla creates ___.

L5

Answer 60

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)

Question 61

Creation of Concentrated urine

L5

Answer 61

→ 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

Question 62

Vasopressin (AVP)

L5

Answer 62

→ 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

Question 63

What stimuli controls vasopressin secretion?

L5

Answer 63

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

Question 64

Magnocellular neurosecretory cells (MNC’s)

L6

Answer 64

→ 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

Question 65

What creates hyperosmotic interstitium and keeps it like that?
L6

Answer 65

→ 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

Question 66

Renal countercurrent exchange system

L6

Answer 66

→ 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

Question 67

Active transport in the loop of Henle

L6

Answer 67

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)

Question 68

How does the vasa recta remove water?

L6

Answer 68

→ 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

Question 69

What’s the main job of the countercurrent multiplier? Exchanger?
L6

Answer 69

→ multiplier: create hypertonic interstitium

→ exchanger: prevent dilution of hypertonic interstitium via picking up water leaving descending

Question 70

If we ingested 9g of NaCl what would happen (this is daily av of an American diet)
L6

Answer 70

→ 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

Question 71

How do we maintain mass balance (in response to salt ingestion)?
L6

Answer 71

→ 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

Question 72

Aldosterone helps to __.

L6

Answer 72

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

Question 73

Aldosterone acting on principle cells

L7

Answer 73

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

Question 74

What drives/inhibits aldosterone secretion?

L7

Answer 74

→ 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

Question 75

Renin-antgiotensin-system (RAS)

L7

Answer 75

→ 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

Question 76

Angiotensin 2 signals what what?

L7

Answer 76

→ 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

Question 77

Hypertension treatment with ANG||

L7

Answer 77

→ use ACE inhibitors (since ACE causes ANG|| activation to bring bp up) will relax vasculature

Question 78

Atrial natriuretic peptide (ANP)

L7

Answer 78

→ 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

Question 79

ANP affects:

L7

Answer 79

→ 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)

Question 80

Potassium Balance

L7

Answer 80

→ 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

Question 81

Why is potassium balance important?
Hyper and hypokalemia?
Issues with them?
Causes of K balance disturbances?
L7

Answer 81

→ 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

Question 82

Behavioural responses for salt and water balance

L8

Answer 82

→ 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

Question 83

Thirst stimulus and process

L8

Answer 83

→ 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

Question 84

What physiological changes influence inc Na appetite?

L8

Answer 84

→ inc aldosterone
→ inc angiotensin
→ changes in [Na] in brain

Question 85

Avoidance behaviours

L8

Answer 85

help prevent dehydration
ex, desert animals avoid heat of day and move at night (nocturnal)
ex, midday siesta in hot places

Question 86

Osmolarity and blood volume change independently resulting in 8 different senarios
L8

Answer 86

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)

Question 87

Responses to changes in vol and osmolarity (4)

L8

Answer 87

→ 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

Question 88

Severe dehydration responses

L8

Answer 88

i.e. ECF vol loss, bp dec, osmolarity inc
→ conserving fluids
→ cardiovasc reflexes inc bp
→ thirst stimulated

Question 89

4 compensatory mechanisms to dehydration are:

L8

Answer 89

*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)

Question 90

“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

Answer 90

Osmolarity reigns and aldosterone is not secreted

→ if it was, Na would be reabsorbed which would worsen the already high osmolarity