module 4: renal physiology Flashcards
1
Q
what homeostatic function are the kidneys involved in
A
reg electrolytes, acid-base control, blood volume control, and regulation of blood pressure
1
Q
ICF
A
fluid IN cells, 2/3 of body fluid
2
Q
ECF
A
fluid AROUND cells (plasma, interstitial fluid, lymph, transcellular fluid)
1/3 of body fluid
3
Q
plasma and interstitial fluid are separated by…
A
blood vessel walls
4
Q
at the level of the capillaries how does everything in plasma, water, etc exchanged
A
freely exchanged with the interstitial fluid
5
Q
the composition of plasma and interstitial fluid are essentially…
A
identical
6
Q
what stands in btwn the ICF and ECF, what is not exchanged
A
the barrier is the plasma membrane that surrounds each cell in the body. ICF contains proteins that do not exchange with the ECF.
7
Q
how does the barrier between ECF and ICF work
A
there is an unequal distribution of ions across this barrier. the barrier does not allow passive movement of either ICF or ECF constituents across the plasma membrane, preventing them from equilibrating through the process of diffusion
8
Q
why is ECF volume regulated
A
to maintain blood pressure. maintenance of salt balance is important in the long-term regulation of ECF volume.
9
Q
why is ECF osmolarity
A
to prevent the swelling or shrinkage of cells
10
Q
Intracellular Fluid (ICF)
A
Stores 2/3 of the body water; fluid within the cells
11
Q
Extracellular Fluid (ECF)
A
1/3 of body water; plasma (1/5) and interstitial (4/5) fluid
12
Q
Transcellular Fluid
A
Water in epithelial-lined spaces; lymph, CSF, negligible amounts
13
Q
what are compartment barriers
A
The “major pools” of water are separated by barriers
14
Q
what are the 2 compartment barriers
A
Plasma/Interstitial Fluid Barrier
ICF and ECF Barrier
15
Q
Plasma/Interstitial Fluid Barrier
A
Separated by the walls of blood vessels except at the capillaries where everything except for proteins are freely exchanged between plasma and interstitial fluid
Plasma/Interstitial Fluid composition (both ECF) are practically the same except for the proteins; changes in one reflect in the other pool because of the capillaries
16
Q
ICF and ECF Barrier
A
The plasma membrane surrounding each cell which regulates what goes in and out of the cells; ICF has proteins that ECF does not, there is an uneven ion distribution
Ex., K+ and PO43- is ICF, Na+ and Cl- is ECF; no passive ion movement across for equilibrium
17
Q
ECF Volume and Osmolarity
A
Ultimately, overall fluid balance in the body is dependent on regulating the ECF
Components exchanged in the ICF come from ECF water, other constituents
18
Q
ECF Volume Regulation
A
Regulated to maintain blood pressure; salt balance also regulates volume
Direct influences on BP by changing plasma volume -> arterial BP is adjusted
19
Q
ECF Short-Term Control
A
Minor changes; works with what you have
- Baroreceptor Reflex: Carotid artery/Aortic arch mechanoreceptors detect BP changes and signal ANS; increase total peripheral resistance/cardiac output when low, decreases when high
- Fluid Shifts: Fluids temporarily shift out of the interstitial fluid and into the plasma or vice-versa
20
Q
ECF Long-Term Control
A
Larger, input/output changes
- Kidneys: Controls urine output and regulates fluid output
- Thirst Mechanism: Controls fluid input into the diet
21
Q
ECF Salt Balance
A
Sodium and anions (Cl- + Bicarb) make up 90% of ECF solutes; water follows salt (osmosis)
Salt Input: Only dependent on dietary salt; we only need to replace 0.5g/day from feces/sweat
Average Canadian input is 3.5g of salt a day
Salt Output: Excess salt (~3.0g dietary) must be eliminated in the kidneys (feces/sweat = 0.5g)
Kidneys have the greatest role in output and control is very precise
22
Q
ECF Osmolarity
A
A measure of the concentration of a solute in solution; high = more solute/less water
Water moves down its concentration gradient until osmotic pressure equalizes
This is highly regulated to prevent cell volume changes (swelling/shrinking)
23
Q
Hypertonic
A
The solution has a higher solute concentration vs. another solution across a membrane
- Water flows into this solution to equalize solute concentration (less water)
- Water moves from the cells into the ECF (shrinking); has 3 main causes:
1. Diabetes Insipidus: Deficiency in ADH/vasopressin; no water retention
2. Insufficient Water Intake: Not drinking enough water
3. Excess Water Loss: Heavy sweating, extreme exercise, vomiting, diarrhea
24
Hypotonic
The solution has a lower solute concentration vs. another solution across a membrane
Water flows out from this solution to equalize solute concentration (more water)
Water moves from the ECF into the cells (swelling, burst); impairs cellular function, 3 main:
1. Renal Failure: Cannot produce concentrated urine, must filter with dialysis to treat
2. Rapid Water Ingestion: More water intake vs. amount kidneys can filter out at a time
3. Oversecreted Vasopressin/ADH: Promotes water retention
25
Isotonic
The solution has equal osmolarity compared to normal body fluids; ex., N/S (NaCl 0.9%)
Injected into blood plasma within veins (1/5 ECF), it is isotonic, so no net fluid shift between ECF and ICF, prevents fluctuations in intracellular volume
No osmotic gradient = no net fluid shift
26
Water Balance Regulation: Hypothalamic Osmoreceptors
Constant brain monitoring of surrounding fluid osmolarity (plasma)
Increased Osmolarity: High conc., low fluids = Stimulates ADH/Vasopressin release, thirst
Decreased Osmolarity: Low conc., high fluid = Inhibits ADH/Vasopressin, no thirst
Vasopressin: Postpit hormone that acts on kidney tubule to increase water absorption
Thirst: Stimulates the intake of water through drinking
27
Water Balance Regulation: Left Atrial Volume Receptors
Monitors LA BP; activated during >7% ECF volume/BP loss
Receptors stimulate the hypothalamic ADH/Thirst pathways
28
Describe an overview of the kidneys
Organs that function to maintain the ECF volume, electrolyte composition, osmolarity
Has neural/endocrine (hormonal) inputs for control
Increases and reduces elimination in excess of water or electrolytes
Cannot actively correct a deficiency (can correct surplus); just slow down elimination
29
describe the structure of the kidneys
- ~10cm bean-shaped organs, each has an adrenal gland on top
- Has outer renal cortex (with nephrons), and inner renal medulla (renal pyramids, tubules)
- Inner core has a renal pelvis that channels urine into ureter towards the bladder
- Nephron: Functional unit of the kidney; filters blood, reabsorbs fluids/molecules, makes urine
~1,000,000 per healthy kidney
30
Kidney Major Functions
- Water Balance: Plasma volume regulation
- Body Fluid Osmolarity: Keeps the fluid isotonic to prevent fluid shifts
- Solutes: Regulates ECF solutes (Na+, K+, Cl-, Ca2+, PO43-); Acid-Base Balance
- Excretion: Metabolic waste excretion, ingested foreign compounds
- Hormonal: Produces erythropoietin (EPO), renin, vitamin D
31
What are the 6 vascular parts of the nephron
The portion that supplies blood to the nephron
1. Renal Artery: The artery through which blood enters the kidneys and further subdivides into:
2. Afferent Arteriole: Brings the blood into the nephron to the glomerulus (1:1 supply)
3. Glomerulus: A ball-like capillary that filters out solutes and water (plasma) from the blood
About 20% of blood is filtered and enters the renal tubules for filtrate concentration
Remaining 80% is not fully “filtered” until it leaves via renal vein
No gas exchange occurs at this capillary; arterial blood stays oxygenated
4. Efferent Arterioles: Arteriole that carries unfiltered blood (80%) from the glomerulus into the secondary capillary beds for further tubular exchange between the blood/filtrate
5. Peritubular Capillaries: Secondary capillary bed; gas exchange occurs, supplies oxygen to the renal tissues for perfusion
6. Renal Vein: Returns filtered blood back to the heart
32
the tubular component of the nephron
Carries the filtrate throughout the nephron until the renal pelvis as a continuous tube separated into several segments with distinct structures and functions
1. Bowman’s Capsule: Encircles the glomerulus; collects the fluid filtered from its capillaries
2. Proximal (Convoluted) Tubule: Highly coiled tube within the renal cortex after the capsule
3. Loop of Henle: Forms a hairpin loop that dips down into the renal medulla
Descending Loop: Travels from the cortex to the medulla
Ascending Loop: Travels from the medulla to the cortex, passes through the juxtaglomerular apparatus, a fork between afferent/efferent arterioles
4. Distal (Convoluted) Tubule: Another highly coiled tube within the renal cortex after the loop
5. Collecting Duct: A long duct that collects filtrate from nephron tubules, draining into pelvis
6. Renal Pelvis: Area in the kidney core that channels urine into the ureters to the bladder
33
what are the 2 nephron types
1. cortical nephrons
2. juxtamedullary nephrons
34
Cortical Nephrons
Glomeruli are in the outer cortical layers; about 80% of nephrons
- Serves secretory and regulatory functions
- Loops of Henle are short, only have slight medullary dips; peritubular capillaries wrap around it
35
Juxtamedullary Nephrons
Glomeruli are in the inner cortical layers; about 20% of nephrons
- Responsible for concentrating and diluting urine (via countercurrent exchange)
- Long loops of Henle deep in the medulla for urine concentration
- Peritubular capillaries form vasa recta hairpin loops close to the long loops for exchange
36
Glomerular Filtration (GF)
Only about 20% of blood flowing through the glomerulus is filtered into the capsule; protein-free but has all plasma solutes
The rest of the blood exits via the efferent arteriole and filtered by tubular secretion (80%)
37
Glomerular Filtration Rate (GFR)
Normally about 125mL formed per minute (125mL/min)
38
Tubular Reabsorption (TR)
Filtrate flowing through the tubules has many important substances returned to the capillaries through reabsorption
Also uses selective transfer of substances by mediator proteins
39
Tubular Secretion (TS)
Secondary route for blood substances to enter renal tubules
Allows for the selective transfer of substances from the capillaries to the tubules
This is where the remaining 80% of plasma contents are excreted from the blood
40
glomerulus
Capillary network at the nephron start; blood filters across its walls, through the membrane to form filtrate in Bowman’s Capsule to enter the tubules
Receives blood supply from afferent arterioles, exits via efferent arterioles
41
Glomerular Filtration Rate
The rate at which blood is filtered through all glomeruli
- Measures overall renal function; approximately 125mL/min men, 115mL/min women
42
Glomerular Filtration
The plasma passes through three layers making up the glomerular membrane
43
Glomerular Capillary Wall
Single layer of endothelial cells, but pores are large, 100x more permeable to fluids/solutes vs. normal capillaries
Everything except large plasma proteins (ex., Hb) pass; small proteins (ex., albumin) do
44
Basement Membrane
No cells; collagen network that provides structural strength, negatively charged glycoproteins that repel, discourage small protein filtration (albumin is negative)
Only 1% of filtered albumin actually passes into the capsule
45
Inner Layer of Bowman’s Capsule/Podocytes
Cells that wrap around the glomerular capillaries; forms narrow filtration slits that allow fluid to pass between, into Bowman’s capsule
46
Glomerular Capillary Blood Pressure
Pressure exerted by the blood in the glomerular capillaries
About 55mmHg (outwards), compared to 18mmHg in normal capillaries
Afferent arterioles = LARGE diameter vs. efferent, there is more resistance to blood leaving the glomerular capillaries as pressure is constant along its length (like big water, small hose)
47
Plasma-Colloid Oncotic Pressure
Large, unfilterable plasma proteins pull water (oncotic force)
About 30mmHg (inwards) to resist water movement into Bowman’s capsule
48
Bowman’s Capsule Hydrostatic Pressure
Capsular Fluid pressure pushing back on capillaries
ABout 15mmHg (inwards) to resist water movement
49
Net Filtration Pressure
55mmHg - 30mmHg - 15mmHg = 10mmHg outwards
These values are generally stable, except in pathology
Ex., kidney stone blocks renal pelvis, increases tubular pressure -> decreases GFR
Ex., dehydration (diarrhea), decreases capillary pressure (less volume), increases plasma colloid resistance to prevent filtration
50
Glomerular Filtration Rate
Depends on filtration pressure and filtration coefficient (KF), determined by membrane permeability and glomerular surface area available
GFR = Filtration Pressure * KF = 125mL/min (M), 115mL/min (F)
51
does regulating the glomerular capillary BP (afferent arteriole) affect net filtration pressure
GCBP (Afferent Arteriole Vasoconstriction/Dilation) -> FP -> GFR
52
Intrinsic Mechanisms controlled GFR regulation
Autoregulatory; prevents sudden GFR swings by regulating arteriole diameter
Dilation increases pressure (Big water small hose); Constriction decreases pressure
In essence, these are oppository to sudden changes to keep it stable
53
2 intrinsic mechanism for controlled GFR regulation examples
- myogenic activity
- tubuloglomerular feedback (TGF)
54
Myogenic Activity
Smooth Muscle Myogenic Response; Increased pressure stretches afferent walls and an opposing constriction to reduce blood flow, prevent GFR changes
If BP decreases (less stretch), arterioles dilate to increase BP, prevent GFR changes
55
Tubuloglomerular Feedback (TGF)
At the juxtaglomerular apparatus, there are special tubular cells called the macula densa that detect tubular fluid salt changes
Increased pressure = GFR = fluid = More salt
ATP Release -> Adenosine -> Afferent Arteriole Vasoconstriction, lowers GFR
Or Low Pressure -> Less Adenosine, Dilation, Higher GFR
56
Extrinsic Mechanisms
SympNS afferent arteriole innervation independent of arterial BP fluctuations
Ex., in haemorrhage -> blood volume loss, arterial pressure drop -> baroreceptor reflex
At the kidney level -> AA vasoconstriction, decreases GCBP, decreases GFR/urine production
Prevents further depletion of plasma volume
57
summary of controlled GFR regulation
BP drop -> Baroreceptors -> SympNS Vasoconstriction -> Kidney AA, GCBP decrease -> less GFR -> Less urine -> More fluids/salt conserved -> Long term arterial BP increase
58
describe kidney and cardiac output
- About 20% of plasma entering kidneys becomes glomerular filtrate
- Average GFR = 125mL/min (20%) -> x5 = 625mL/minute for kidney plasma blood flow
- Plasma is 55% of blood; 625 / 0.55 = 1,140mL/minute of whole blood
- Total CO at rest (70mL*70bpm) ~= 5,000mL/minute at rest; 1,140/5,000 = 22% of output
The kidneys receive 22% of cardiac output despite only accounting for 1% of total body weight
- Why? They receive so much blood due to their importance for “cleaning”, filtration of the blood to help with tight volume, electrolyte control, waste elimination
59
describe tubular reabsorption
The processes returning water, other essential solutes back into plasma while allowing waste products to remain in filtrate; has two steps
1. Tubule to Interstitial Space: Uses passive or active substance movement
2. Interstitial Space to Bloodstream: Uses passive movement
Highly selective and variable between substances; essential substances are almost totally reabsorbed (H2O, Na+, Glucose); wastes are mostly filtered (urea, phenol)
60
describe tubular cells, liminal membrane and basolateral membrane
The epithelial cells that line the tubule and are responsible for reabsorption
- Luminal Membrane: Area of the epithelial cells in contact with the tubule lumen
- Basolateral Membrane: Area of epithelial cells in contact with the interstitial fluid
61
what is the path for tubular reabsorption
Tubule Lumen -> Luminal -> Tubular Cytosol -> Basolateral -> Interstitial -> Peritubular Capillary
Tubular cell membranes are not in contact other than tight junctions; reabsorbed substances must move through the tubular cell into the interstitial space (no choice)
62
describe transepithelial (transcellular) transport
The movement of solutes across an epithelial cell layer through the cell
1. Reabsorbed substances crosses the luminal membrane
2. Substance passes through the cytosol
3. Substance crosses the basolateral membrane
4. Substance diffuses across the interstitial fluid
5. Substance crosses the capillary wall and re-enters the plasma
This procedure can be either passive or active
63
Sodium Transepithelial Transport
99.5% of filtered Na+ is reabsorbed; highly controlled
64
Sodium Reabsorption
Reabsorbed in various extents across the entire tubule unlike other solutes
65
Proximal Tubule & Na+ for sodium transepithelial transport
~67% of sodium is reabsorbed here to create a gradient for the reabsorption of other things -> glucose, amino acids, water, Cl-, urea
66
Ascending Loop of Henle & Na+ for sodium transepithelial transport
~25% of total Na+ is reabsorbed; (NaCl) is essential to either concentrate or dilute the urine depending on body needs (countercurrent multiplication)
67
for sodium transepithelial transport
~8% of total Na+ is reabsorbed but this is under hormonal control to regulate ECF volume and secretion of K+ and H+; can increase or decrease
68
sodium transporters: Na+-K+-ATPase Pump
Actively transports Na+ across the basolateral membrane into the interstitial fluid; accounts for about 80% of the kidney’s energy needs
Keeps tubular cell Na+ concentration low; allows passive Na+ diffusion from lumen to tubular
69
Sodium-Glucose Co-Transporter (SGLT)
In the proximal tubule, sodium is passively carried by a co-transporter along with organic nutrients like glucose or amino acids
Secondary Active Transport: The transport method of glucose/amino acids since they use the concentration gradient of Na+ created by the NaKATPase pump
70
Sodium Channels
In the collecting ducts; Na+ passively enters the cells by a channel alone
By here, the collecting ducts tend to have very concentration, high osmolarity urine
71
describe Hormonal Regulation of Sodium
Occurs in the DCT (PCT/Loop are constant); ~8% of the Na+ is subject to hormonal control under the Renin-Angiotensin-Aldosterone System (RAAS)
72
renin secretion triggers
1. Renin Secretion: Granular cells in the juxtaglomerular apparatus detect BP drops -> renin
2. Sympathetic Innervation: Granular cells can be triggered to secrete renin by SympNS activity
Ex., baroreceptor reflex in low BP
3. Macula Densa Cells: Cells on the tubular portion of the juxtaglomerular apparatus; sensitive to Na+ decreases and decreased luminal Na+ triggers renin secretion
73
RAAS Procedure
1. Angiotensinogen is released by the liver; present in high plasma concentrations
2. Renin acts like an enzyme; turns angiotensinogen to Angiotensin I
3. Angiotensin-Converting Enzyme (ACE) in the lungs turns A1 -> Angiotensin II
4. Angiotensin II stimulates the adrenal cortex (glomerulosa) to release Aldosterone
5. Aldosterone acts on the distal/collecting tubules to increase Na+ reabsorption
a) Tubular Cells increase insertion of passive Na+ channels in the luminal membrane and Na+-K+-ATPase pumps in the basolateral membrane
High K+ from pump diffuses out through K+ channels into lumen (hypoK+)
b) There is a greater passive flow of Na+ out the tubular fluid
c) Increases both Na+ and water retention (water follows salt), higher BP
K+ is wasted
74
atrial natriuretic peptide (ANP)
Counterregulatory to aldosterone; reduces Na+ load and BP
Higher blood volume/venous return, left atrium/aortic arch/carotid sinus stretch receptors stimulate the release of ANP which does 3 things
1. Na+ Reabsorption Inhibition: DCT inhibition to excrete more Na+ in the urine (8%)
2. Renin/Aldosterone Inhibition: Prevents RAAS from conserving salt/water
3. Afferent Arteriole DIlation: Results in increased GFR; filters out more salt and water
75
Transport/Tubular Maximum (TM) and Renal Threshold
The limit of how much of a substance can be actively reabsorbed by the kidneys due to a limited amount of carrier proteins in the plasma membrane
Renal Threshold: The point after which any excess reabsorbed substance concentration will be excreted in the urine
Substances with TM’s may or may not be regulated by the kidneys/hormones
I.e., phosphate is, glucose is not
76
describe Phosphate & Kidneys
Normal circumstances; [PO4^3-] is the same as renal threshold
Huge spike in [PO4^3-] after a meal; the rest is filtered out
The excess dietary phosphate is filtered in the urine and concentrations return to normal, but the renal threshold can be modified by hormones depending on the body’s needs
77
PO4 & Parathyroid Hormone
Alters Ca, PO4 renal thresholds and adjusts conserved electrolytes
PTH decreases PO43- reabsorption and increases Ca2+ reabsorption (inversely related)
PO4 drop = Ca raise -> Suppresses PTH -> increased PO4 reabsorption -> normal [PO43-]
78
PO4 & Vitamin D
Changes intestinal reabsorption of both PO4 and Ca2+
Decreased [PO4] -> more kidney Vit. D activation -> more Ca2+, PO4 intestine reabsorption -> normal [PO4] levels
79
Glucose & Kidneys
Not regulated by the kidneys; normal plasma [glucose] = 100mg/100mL (1dL)
Freely filtered; plasma concentration = filtrate concentration
GFR = 125mL/min * 100mg/100mL = 125mg/min glucose filtered by the kidneys
This is proportional by concentration; 200mg/100mL = 250mg/min
80
normal glucose TM
375mg/min; any filtered load <375mg/min is fully reabsorbed
At a GFR of 125mL/min, 300mg/dL glucose will be reabsorbed
Beyond 300mg/dL, excess plasma glucose = glycosuria -> diabetics
Splay: Difference in expected Tm of glucose vs. what actually occurs
81
Splay
Difference in expected Tm of glucose vs. what actually occurs
- 300mg/dL or 375mg/min vs. ~160-180mg/dL or 200-225mg/min
- Only reabsorbed in the PCT, carriers get overwhelmed -> glycosuria
- Possibly because co-transporters are shared with amino acids; not well explained
82
how are Kidneys & Chloride, Water, Urea reabsorbed
All reliant on the active Na+ reabsorption mechanism (2ary)
83
how is water reabsorbed
Passively reabsorbed along the whole tubule following sodium through aquaporins
- 65% in the PCT, 15% in the loop, 20% in the DCT/Collecting (178.5/180L)
- Amount reabsorbed in the DCT depends on hydration state and hormones (ADH)
84
how is chloride reabsorbed
- Not directly regulated by kidneys despite high concentration, no transepithelial transport but leaves the tubule by moving between epithelial cells
- Down the electrochemical gradient and follows Na+ reabsorption
- Amount of Cl- reabsorbed depends on amount of Na+ reabsorbed
85
how is urea reabsorbed
About half is reabsorbed despite it being a protein breakdown waste product
- No net diffusion at the start of the PCT (same concentration), but filtrate becomes more and more concentrated as the water is reabsorbed (2/3 fluid loss = 3* higher [urea])
Passively reabsorbed towards the end of the PCT
- Only ~50% of the urea is excreted/filtered; other 50% remains in blood -> BUN
- Blood Urea Nitrogen (BUN) accumulates in renal failure, measurable indicator
86
Tubular Secretion
The movement of substances from the peritubular capillaries to the tubule lumen for the removal of substances from the body
Also occurs via transepithelial transport; mostly H+, K+, and organic anions/cations
87
hydrogen ion secretion
The extent depends on plasma acidity; high H+, more, low = less secreted
Occurs in the PCT, DCT, and Collecting Tubules (all, not loop)
Plays a key role in acid-base balance
88
potassium ion secretion and K+ recycling
Undergoes both tubular reabsorption and tubular secretion
Freely filtered in the glomerulus; actively reabsorbed in the PCT, generally unregulated
K+ Recycling: Passive K+ Channels are in the basolateral membrane; when basolateral Na-K-ATPase pumps pump K+ into the cell, they diffuse back into the interstitial space
No net effect on K+ and allows Na+ reabsorption
- Secretion is variable and subject to regulation; high plasma [K+] = high DCT secretion
- Active secretion depends on the Na+-K+-ATPase pump in the DCT; most K+ is reabsorbed in the PCT, there is low [K+] in the DCT, diffuses freely into tubule through luminal K+ channels
Unlike the PCT where K+ is recycled, it is not in the DCT
89
K secretion regulation for Na/K
- Rise in Plasma K+ -> Aldosterone release from adrenal glands; Na+ saving, K+ wasting
- Decreased plasma Na+, volume, arterial BP (aldosterone triggers) also stimulates K+ secretion but may lead to K+ depletion/hypokalemia
90
K+ Secretion Regulation for H+ Secretion
- Acid-Base body status; Na+-K+-ATPase pump on basolateral DCT membranes can substitute H+ for K+; in acidic conditions, H+ will be moved into tubular cells
- Limited carriers = less K+ moves out, leads to hyperkalemia
91
PCT has 2 types of secretory carriers what for...
1 for anions
1 for cations
92
why are the 2 types of secretory carriers important (for what 3 reasons)
1. Increases Excretion: More organic ions in the tubular fluid increases amounts of ions excreted compared to GFR alone; chemical messengers like NE, histamine, prostaglandins
- Aims to reduce/limit biological activity
2. Excretes Poorly Soluble Organic Ions: Organic ions are hydrophobic, protein-bound (not filtered), only a small, non-bound fraction is filtered
- Tubular secretion can remove the unbound fraction, cause more equilibrium unloading to excrete more of the highly bound ions
3. Removes Foreign Compounds: Foreign organic ions like food additives, drugs, pesticides, pollutants are removed by these transporters (ex., SLC/OAT and penicillin)
- Kidneys routinely remove these; no regulation to increase removal if needed
93
describe plasma clearance
The concept of “cleaning” or clearing substances from the plasma by eliminating them in the urine, definable for any substance as the volume of plasma (not substance) completely cleared of that substance by the kidneys per minute
- The amount of plasma volume totally cleared of a substance per unit of time
- Assumes the kidneys effectively remove all of the substance from the plasma
- Out of 125mL/min GFR, 124mL/min is reabsorbed -> 1mL/min of urine is made, 1.5L/day, all waste products concentrate in the urine
Clearance Rate (mL/min) = (Urine Concentration [amount/mL] * Urine Flow Rate [mL/min]) / Plasma Concentration (Quantity/mL)
94
types of plasma clearance (3 types)
Varies depending on how different substances are handled
1. Filtered, Not Reabsorbed
2. Filtered and Reabsorbed
3. Filtered and Secreted, Not Reabsorbed
95
1. Filtered, Not Reabsorbed
Plasma Clearance
- Tends to estimate GFR; ex., onion/garlic inulin (freely filtered, no reabsorption) -> 30mg/mL urine * 1.25mL urine/min / 0.3mg/mL plasma = 125mL/min
- Hard to use for measuring GFR since it needs to be continuously infused
- CREATININE (Cr) is used instead; end muscle metabolism product continually made, used to estimate GFR and has a relatively steady concentration, not reabsorbed (minor secretion)
96
2. Filtered and Reabsorbed
Plasma Clearance
Clearance is less than GFR
- Ex., glucose -> normal conditions, all glucose is reabsorbed -> Cl = 0
- Ex., urea -> normally, 50% is reabsorbed -> Cl = 62.5mL/min
97
3. Filtered and Secreted, Not Reabsorbed
Plasma Clearance
Clearance tends to be higher than GFR
- Ex., H+ ions which are both filtered out then additionally secreted into the tubule
- If GFR is 125mL/min, and amount of H+ in 25mL plasma is secreted per minute
- CLH+ = 150mL/min
98
describe vertical osmotic gradient
- Occurs in the medullary interstitial fluid; a shift of normal osmolarity from 300mOsm/L to 1200mOsm/L towards the renal pelvis
- Urine from 100-1200mOsm/L can be produced depending on body’s hydration state
99
describe cortical vs. juxtamedullary
- Cortical loops of Henle only dip slightly; Juxtamedullary loops and vasa recta dip all the way to the renal pelvis
- Flow in the loop/vasa recta go into opposite directions; undergoes countercurrent flow
100
describe Juxtaglomerular Loop of Henle and the VOG
1. Once fluid leaves Bowman’s Capsule into the PCT, lots of Na+ is actively reabsorbed; water wants to follow this (it is secondary is Na+)
2. At the end of the PCT, 65% of filtrate volume is reabsorbed, but tubular fluid is still isotonic at 300mOsm/L
3. The descending loop is permeable to water (15% reabsorbed), Ascending loop is only permeable to Na+ ions and water cannot follow
101
Descending fluid movement
Water and ions can move, so it equilibrates with the interstitial space
102
ascending fluid movement
Only ions can move and they are actively pumped out (to a 200mOsm difference)
103
hypothetically how is the VOG established?
1. PCT -> Loop starts at 300mOsm/L; isotonic with interstitial space, no movement
2. Ascending pumps Na+ to interstitial space (200mOsm vs. 400mOsm), this equilibrates with the Descending limb which is now 400mOsm
3. New fluid comes in and pushes the 400mOsm fluid to the ascending limb and Na+ is actively transported out, maintains the 200mOsm difference (layers with 400 vs. 200, 600 vs. 400)
4. As fresh filtrate enters again and again, this increases interstitial osmolarity which equilibrates with the descending limb and the ascending limb decreases in osmolarity to maintain the 200mOsm gap
- Eventually, you will have layers of concentration gradient as equilibration cycles go
5. Eventually, equilibrium is established; there is a VOG and tubular fluid has a max osmolarity of 1200mOsm/L at the bottom of the loop and 100mOsm/L at the start of the DCT
- Max osmolarity is 4x body fluid osmolarity, minimum is 1/3 normal
- Once incremental gradient is established, it stays constant due to continuous fluid flow and active solute transport into the interstitial fluid
104
why hypothetically is this the way VOG is established
1. The VOG in the medullary interstitial fluid allows the collecting ducts to form either very concentrated or very dilute urine vs. normal body fluid
2. Significantly reduces the overall urine volume to conserve body salts, water
105
describe vasa recta countercurrent exchange
Blood supply to the renal medulla, differs from countercurrent multiplication
- Hairpin shape is closely associated with descending/ascending loops, highly permeable capillaries to both NaCl and H2O
- Vasa Recta flow is countercurrent, or opposite the flow of fluid through the loop (descends while loop ascends), and travels through the medulla where fluid osmolarity is 1200mOsm/L
106
describe countercurrent exchange
The passive solute/H2O exchange between the vasa recta limbs and the interstitial fluid
1. Efferent Arteriolar Blood is isotonic (300mOsm/L) as it leaves the renal cortex
2. In the Descending Vasa Recta Loop, it equilibrates with the interstitial medulla (reabsorbs Na+, H2O exits)
- At the bottom, it now has the same 1200mOsm osmolarity
3. As blood flows up, the opposite occurs; reabsorbs H2O, Na+ exits, stays hypotonic
- At the cortex near PCT again, osmolarity normalizes to 300mOsm/L, isotonic
Note that nothing happened to blood osmolarity; blood because vasa recta handed off nutrients and oxygen to the medullary cells without affecting itself or the vertical osmotic gradient
107
describe water reabsorption and its regulation in the DCT
1. Vasopressin/Antidiuretic Hormone is released by the posterior pituitary in water deficit (hypertonic) and inhibited in hypotonic/high fluid
2. ADH acts on the DCT cells to release aquaporin molecules onto the luminal membrane which allows for more water to be passively reabsorbed into epithelial cells
3. Water passively moves into the interstitial fluid/plasma once in cells; ADH does not act on the loop or PCT with 80% of reabsorption, only last 20% in DCT/collecting tubules
108
describe water reabsorption regulation
1. water deficit
2. water excess
DCT has 100mOsm/L osmolarity; water very much wants to leave the tubules especially as it plunges towards the 1200mOsm pelvis, but can only do this with vasopressin
1. Water Deficit: High ADH; lots of aquaporin channels in DCT; urine is maximally concentrated to 1200mOsm/L; output can be as low as 0.3mL/min
2. Water Excess: Low ADH; body fluid osmolarity <300mOsm/L but DCT fluid preserved at 100mOsm/L; worst case with no ADH at all = no aquaporin inserted, no water reabsorbed
- Minimally concentrated urine at 100mOsm/L; output as high as 25mL/min
109
water reabsorption can follow solute reabsorption... but also independently describe it
Tubule segments permeable to water will follow solutes due to osmosis
- Reabsorbed solute = reabsorbed water; excreted solute = excreted water
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Osmotic Diuresis
With excess, un-reabsorbed solute in the tubule, water is also excreted as it follows the solute via osmosis
- Ex., diabetics with high blood glucose, glucose exceed TM and glucose in the tubule has an osmotic pull on the water -> more water is excreted
- A symptom of diabetes is excess urine production and thirst
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Water Diuresis
- Increased excretion of water with little/no change in solute excretion
- In cases where vasopressin/ADH is suppressed (no aquaporins); ex., alcohol consumption
- The kidneys generate a dilute urine in greater volumes vs. alcohol consumed
- Dehydration when drinking alcohol is a thing (happy St. Pat’s)
112
where is urine usually stored
From the renal pelvis, urine is transmitted through the ureters to the bladder via peristalsis
Normally, there is no backflow unless enough pressure is generated
113
what is the bladder
Composed of smooth muscle with specialized epithelial lining; can expand to increase storage capacity and is innervated by the PSNS (stimulation = bladder contraction)
Exits are guarded by the internal/external urethral sphincters
114
what is the internal urethral sphincter
Involuntary, technically a part of the bladder wall, not a true sphincter
Relaxed bladder = urethral outlet is closed
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what is the external urethral sphincter
Encircles the urethra, supported by the pelvic diaphragm
- Kept closed by constant, tonic motor neuron firing
- VOLUNTARY control, skeletal muscle, can tighten to prevent urination despite contractions
116
what is micturition
Urination; the process of the bladder emptying controlled voluntarily and by reflex
117
what is micturition reflex
Bladder holds 250-400mL before internal bladder wall pressure initiates a stretch reflex to activate afferent fibres to the spinal cord
1. Interneurons activate PSNS to stimulate bladder contractions, external sphincter relaxation
2. Internal Sphincter opens on its own as bladder changes shape in contraction
- BOTH sphincters must be open in order for urine to be expelled
- Reflex evident in infants who void once bladder fills enough
118
describe voluntary control with micturition reflex
Overrides micturition reflex by learning perception of bladder filling prior to reflex activation -> cerebral cortex voluntary excitatory signals override reflex, keeps motor neuron for external sphincter activated and therefore closed
- Voluntary motor neuron inhibition causes urination when both sphincters are open
- If held long enough, pressure-activation reflex is stronger than voluntary control
- Incontinence -> Bladder empties uncontrollably
