1
Q
What are the two major compartments of body fluid?
A
Intracellular Fluid (ICF) – fluid inside cells
Extracellular Fluid (ECF) – fluid outside cells
2
Q
What is the Intracellular Fluid (ICF)?
A
- Fluid within cells
- Makes up about two-thirds of total body fluid
3
Q
What is the Extracellular Fluid (ECF)?
A
- Fluid surrounding cells
- Includes:
Plasma – ~1/5 of ECF
Interstitial fluid – ~4/5 of ECF
Lymph and transcellular fluid – negligible - Makes up about one-third of total body fluid
4
Q
What is transcellular fluid?
A
- Fluid contained within epithelial-lined spaces
- Examples: cerebrospinal fluid, synovial fluid, digestive secretions
5
Q
What are the three key fluid pools in the body?
A
- Intracellular fluid (ICF)
- Plasma
- Interstitial fluid
These pools remain distinct due to barriers between compartments.
6
Q
How is the extracellular fluid distributed?
A
Plasma: 1/5 of ECF
Interstitial fluid: 4/5 of ECF
Lymph and transcellular fluid: negligible
7
Q
Why are barriers between body-fluid compartments important?
A
Barriers limit the movement of water and solutes between compartments to differing degrees, helping maintain distinct compositions and proper cellular function.
8
Q
What separates plasma from interstitial fluid?
A
- Blood vessel walls, specifically capillary walls
- At the capillary level, water and most solutes can freely exchange, except proteins
9
Q
How does the exchange between plasma and interstitial fluid affect their composition?
A
- Plasma and interstitial fluid are essentially identical in composition, except for plasma proteins
- Changes in one compartment are quickly reflected in the other
10
Q
What separates the intracellular fluid (ICF) from the extracellular fluid (ECF)?
A
- The plasma membrane surrounding each cell acts as the barrier
- Proteins in the ICF do not exchange with the ECF
11
Q
How are ions distributed across the plasma membrane?
A
- K+ concentration is higher in the ICF
- Na+ concentration is higher in the ECF
- The plasma membrane prevents passive equilibration of ions between ICF and ECF
12
Q
Why can ICF and ECF not passively equilibrate through diffusion?
A
- The plasma membrane is selectively permeable
- It blocks the passive movement of most ICF and ECF constituents, maintaining unequal distributions of ions and proteins
13
Q
Why is the ECF important for overall fluid balance?
A
All exchanges of water and other constituents between the ICF and the external environment depend on the ECF. While cells regulate their own ICF, overall fluid balance is controlled through ECF regulation.
14
Q
What are the two main factors that are regulated to maintain fluid balance in the body?
A
- ECF Volume – closely regulated to maintain blood pressure; long-term regulation depends on salt balance.
- ECF Osmolarity – closely regulated to prevent cell swelling or shrinkage.
15
Q
How does ECF volume affect blood pressure?
A
Maintaining ECF volume ensures adequate blood volume, which is essential for maintaining blood pressure.
16
Q
Why is regulating ECF osmolarity critical for cells?
A
Regulating ECF osmolarity prevents water from moving excessively into or out of cells, which would cause cell swelling (lysis) or shrinkage (crenation).
17
Q
Define cardiac output.
A
The amount of blood pumped by the heart per minute.
18
Q
Define total peripheral resistance.
A
This is the resistance to blood flow due to the constriction of blood vessels. Higher total peripheral resistance leads to increased blood pressure.
19
Q
How does ECF volume influence blood pressure?
A
ECF volume affects plasma volume, which directly influences arterial blood pressure.
- Increased ECF volume → increased plasma volume → increased blood pressure.
- Mechanisms exist to return ECF volume and blood pressure to normal.
20
Q
What is the baroreceptor reflex and how does it regulate blood pressure?
A
- Baroreceptors are mechanoreceptors in the carotid artery and aortic arch that detect arterial blood pressure changes.
- If blood pressure falls: cardiac output and total peripheral resistance increase → raises BP.
- If blood pressure rises: cardiac output and total peripheral resistance decrease → lowers BP.
- This reflex is part of short-term blood pressure control via the autonomic nervous system.
21
Q
How do fluid shifts help temporarily regulate ECF volume and blood pressure?
A
- Decrease in plasma volume → fluid shifts from interstitial fluid to plasma.
- Increase in plasma volume → fluid shifts from plasma to interstitial fluid.
- These shifts provide temporary compensation for minor changes in ECF volume.
22
Q
What mechanisms are responsible for long-term regulation of blood pressure?
A
- Kidneys control urine output → adjust ECF volume and blood pressure.
- Thirst mechanism regulates fluid intake.
- Short-term mechanisms (baroreceptors, fluid shifts) are temporary, so kidneys and thirst are critical for long-term stability.
23
Q
Which ions account for the majority of solutes in the ECF?
A
Sodium (Na⁺) and its associated anions, mainly chloride (Cl⁻), account for more than 90% of ECF solutes.
24
Q
How does sodium affect ECF volume?
A
Whenever salt (Na⁺ + anions) is transported across a membrane, water follows by osmosis.
Controlling salt levels → controls ECF volume.
25
What is required to maintain salt balance in the body?
Salt input must equal salt output to maintain balance and, by extension, ECF volume.
26
How is salt input regulated?
- Salt input depends on dietary intake and is poorly regulated.
- Daily replacement is needed for loss in feces and sweat (~0.5 g/day for normal activity).
- Average intake for Canadians: ~3.5 g/day, which is much higher than daily losses.
27
How is salt output regulated?
- Salt is eliminated through feces, sweat, and kidneys.
- Kidneys play the greatest role in precise regulation of sodium excretion.
28
Hypertonic means?
A hypertonic solution is one in which the concentration of solutes within that solution is greater than that of another solution that is separated by a membrane
29
What is osmolarity?
Osmolarity is a measure of the concentration of solutes in a solution.
- High osmolarity → more solute, less water.
- Water moves down its concentration gradient until osmotic pressure is equalized.
30
Why is regulating osmolarity important?
It is crucial for preventing changes in cell volume.
Imbalance in osmolarity can cause cells to shrink or swell, impairing cellular function.
31
What happens when there is a decrease in water in the ECF?
- ECF osmolarity increases → ECF becomes hypertonic.
- Water moves out of cells into ECF until osmotic pressure is equalized.
- Cells shrink due to water loss.
32
What happens when there is an increase in water in the ECF?
- ECF osmolarity decreases → ECF becomes hypotonic.
- Water moves into cells until osmotic pressure is equalized.
- Cells expand and, if extreme, can burst.
33
What is the cellular consequence of a hypotonic ECF?
Cells swell, which impairs cellular function and can be dangerous if severe.
34
What is hypotonicity of the ECF usually associated with?
Hypotonicity of the ECF is usually associated with overhydration or excess free water
35
What are the three major causes of hypotonic ECF?
1. Renal failure – kidneys cannot produce concentrated urine.
2. Rapid water ingestion – drinking water faster than kidneys can excrete.
3. Over-secretion of vasopressin – vasopressin promotes water retention.
36
Why must the osmolarity of the ECF be regulated?
To prevent undesirable shifts of water into or out of cells, which can cause cell swelling or shrinkage and impair cellular function.
37
What is a common clinical treatment when hypotonicity is caused by renal failure?
Dialysis is often used to correct the fluid imbalance.
38
What is hypertonicity of the ECF usually associated with?
Hypertonicity of the ECF is usually associated with dehydration and excessive concentration of ECF solutes.
39
What are the three major causes of hypertonicity?
1. Insufficient water intake – not drinking enough fluids.
2. Diabetes insipidus – deficiency in vasopressin.
3. Excessive water loss – due to heavy sweating, prolonged vomiting, or diarrhea.
40
What are the cellular consequences of hypertonicity?
Cells shrink due to water moving out into the hypertonic ECF. This generally decreases normal cell function, with neurons in the brain being particularly sensitive.
41
What are the neurological consequences of hypertonicity?
Shrinking of neurons can lead to confusion, delirium, coma, or death.
42
What does “isotonic” mean?
An isotonic solution has the same osmolarity as normal body fluids, meaning it does not create an osmotic gradient across cell membranes.
43
Into which body water compartment is an isotonic IV solution injected?
The solution is injected into the extracellular fluid (ECF), specifically the blood plasma, which makes up about one fifth of the ECF.
44
What happens to the volume and solute concentration in the ECF after isotonic fluid administration, and how does it affect cells?
- ECF volume increases.
- Solute concentration remains unchanged (ECF stays isotonic).
- No net fluid shift occurs between ECF and ICF.
- Cells neither shrink nor swell, maintaining normal function.
45
How does isotonic fluid loss, such as haemorrhage, impact cells?
- Fluid loss occurs only from the ECF.
- No osmotic gradient is created, so no net fluid shift from the ICF.
- Cells remain unaffected in terms of volume.
46
Where are hypothalamic osmoreceptors located and what is their function?
Hypothalamic osmoreceptors are located in the hypothalamus, near the vasopressin-secreting cells and the thirst centre. Their function is to continuously monitor the osmolarity of the surrounding fluid and help maintain water balance by triggering appropriate physiological responses.
47
What happens when osmolarity increases (hypertonic ECF)?
When osmolarity increases:
- Vasopressin secretion is stimulated.
- Thirst is stimulated.
These responses act together to restore normal osmolarity.
48
How does vasopressin and thirst help correct increased osmolarity?
- Vasopressin (ADH) acts on the kidneys to increase water reabsorption, reducing water loss in urine.
- Thirst increases water intake through drinking.
These mechanisms continue until the hypertonic state is corrected.
49
What happens when the fluid around osmoreceptors is hypotonic?
- Vasopressin secretion is not stimulated (suppressed).
- Thirst is not stimulated.
- This promotes water loss, helping return osmolarity to normal.
50
What are left atrial volume receptors and where are they located?
Left atrial volume receptors are pressure-sensitive receptors located in the left atrium of the heart. They monitor blood pressure and ECF volume.
51
When are left atrial volume receptors activated?
They are activated when there is a greater than ~7% loss of ECF volume and blood pressure.
52
What is the overall role of osmoreceptors and volume receptors in the body?
Together, they integrate osmolarity and volume signals to regulate:
- Vasopressin secretion
- Water intake (thirst)
This ensures stable fluid balance and proper cellular function.
53
How do left atrial volume receptors influence fluid balance?
When activated, they:
- Stimulate hypothalamic pathways
- Increase vasopressin release
- Increase thirst
This helps restore blood volume and fluid balance.
54
Baroreceptor reflex is what type of control (short/long term) to adjust blood pressure through control of the ECF?
Short-term control
55
The kidney's control of urine output is what type of control (short/long term) to adjust blood pressure through control of the ECF?
Long-term control
56
Fluid shifts in/out of the interstitial compartment is what type of control (short/long term) to adjust blood pressure through control of the ECF?
Short-term control
57
The body's control of the thirst mechanism is what type of control (short/long term) to adjust blood pressure through control of the ECF?
Long-term control
58
A change in cardiac output and total peripheral resistance is what type of control (short/long term) to adjust blood pressure through control of the ECF?
Short-term control
59
What regulates the kidneys?
The kidneys are controlled by both neural and endocrine inputs.
60
What is the primary function of the kidneys?
To maintain ECF volume, electrolyte composition, and osmolarity.
61
How do the kidneys respond to excess or deficit of water or solutes?
- Excess water or solutes: kidneys increase elimination.
- Deficit of water or solutes: kidneys cannot actively add them, but can reduce elimination to conserve them.
62
What are the major functions of the kidneys?
1. Maintain water balance
2. Maintain body fluid osmolarity
3. Maintain proper plasma volume
4. Help maintain acid-base balance
5. Regulate ECF solutes (e.g., Na⁺, K⁺, Cl⁻, Ca²⁺, phosphate)
6. Excrete metabolic wastes
7. Excrete foreign compounds ingested
8. Produce erythropoietin
9. Produce renin
10. Activate vitamin D
63
What is the shape and size of the kidneys?
The kidneys are bean-shaped organs, each about 10 cm in length.
64
What structure sits on top of each kidney?
The adrenal gland is situated on top of each kidney.
65
What are the main anatomical regions of the kidney?
- Renal cortex: the outer region
- Renal medulla: the inner region
- Renal pelvis: the central core where urine collects and drains into the ureter
66
What is the functional unit of the kidney?
The nephron, with over one million nephrons per healthy adult kidney.
67
What are the main functions of the nephron?
- Filtration of blood to produce urine
- Reabsorption of necessary fluids and molecules
68
What are the two main components of a nephron?
1. Vascular component – supplies blood to the nephron
2. Tubular component – carries filtrate (urine) through the nephron
69
What is the major part of the vascular component?
The glomerulus, a ball-like capillary network where water and solutes are filtered from plasma.
70
How does blood flow through the nephron’s vascular component?
- Blood enters via afferent arterioles (from renal artery)
- Blood is filtered in the glomerulus
- Remaining blood leaves via efferent arterioles, which then form peritubular capillaries supplying oxygen to renal tissue
71
What is unique about the nephron capillaries?
Arterial blood enters and leaves the glomerulus without oxygen extraction; oxygen delivery occurs via peritubular capillaries.
72
What is the function of the tubular component?
A hollow tube of epithelial cells that transports filtrate/urine to the renal pelvis, with different segments having distinct structure and function.
73
What are the main segments of the tubular component, in order?
1. Bowman’s capsule – encircles glomerulus, collects filtered fluid
2. Proximal tubule – highly coiled, in cortex
3. Loop of Henle – hairpin loop dipping into medulla
- Descending limb: cortex → medulla
- Ascending limb: medulla → cortex, passes juxtaglomerular apparatus
4. Distal tubule – coiled, in cortex
5. Collecting duct – travels through medulla → renal pelvis
74
What is the flow of blood through the nephron?
Renal artery → Afferent arteriole → Glomerulus → Efferent arteriole → Peritubular capillaries → Renal vein
75
What is the flow of solutes through the nephron?
Bowman's capsule → Proximal tubule → Loop of Henle → Distal tubule → Collecting duct → Renal pelvis
76
What are the three basic processes of urine formation?
1. Glomerular Filtration (GF) – filters blood plasma into Bowman’s capsule
2. Tubular Reabsorption (TR) – returns important substances from filtrate to blood
3. Tubular Secretion (TS) – transfers selected substances from blood into tubules
77
What happens during Glomerular Filtration (GF)?
- About 20% of blood plasma in glomerular capillaries is filtered into Bowman’s capsule
- Filtrate is protein-free, but contains the same solutes as plasma
- Rate: ~125 ml/min
78
What happens during Tubular Reabsorption (TR)?
- Filtrate passes through tubules; important substances are returned to peritubular capillaries
- Of 180 L plasma filtered daily, ~178.5 L is reabsorbed
79
What happens during Tubular Secretion (TS)?
- Selective transfer of substances from peritubular capillaries into the tubules
- Allows excretion of substances from the 80% of plasma not filtered in the glomeruli
80
Study Tip for Remembering Reabsorption vs. Secretion
- Body reabsorbs “good” substances and secretes “bad” substances
- Memory aid: “Bad Studies Get Rejected!”
81
Select whether the listed statement is a characteristic of the cortical nephron or juxtamedullary nephron: Lies in outer layer of cortex
Cortical
82
Select whether the listed statement is a characteristic of the cortical nephron or juxtamedullary nephron: Mainly responsible for urine concentration/dilution
Juxtamedullary
83
Select whether the listed statement is a characteristic of the cortical nephron or juxtamedullary nephron: Vasa recta are in proximity to the long loops of Henle
Juxtamedullary
84
Select whether the listed statement is a characteristic of the cortical nephron or juxtamedullary nephron: Primarily serve secretory and regulatory functions
Cortical
85
Select whether the listed statement is a characteristic of the cortical nephron or juxtamedullary nephron: About 80% of all nephrons
Cortical
86
Select whether the listed statement is a characteristic of the cortical nephron or juxtamedullary nephron: Lie within inner layer of cortex
Juxtamedullary
87
Select whether the listed statement is a characteristic of the cortical nephron or juxtamedullary nephron: Peritubular capillaries from hairpin loops of vasculature, called the vasa recta
Juxtamedullary
88
Select whether the listed statement is a characteristic of the cortical nephron or juxtamedullary nephron: Loop of Henle only slightly dips into renal medulla
Cortical
89
What is the glomerulus?
- Network of capillaries at the start of a nephron
- Filters blood through the glomerular membrane into Bowman’s capsule
- Blood enters via afferent arteriole and exits via efferent arteriole
90
What is the glomerular filtration rate (GFR)?
- The total rate of blood filtered through all glomeruli
- Measures overall renal function
91
What are the three layers of the glomerular membrane that filtrate must pass through?
1. Glomerular capillary wall
- Single layer of endothelial cells with large pores
- 100× more permeable than regular capillaries
- Blocks large plasma proteins, but allows small ones like albumin
2. Basement membrane
- No cells; made of collagen (strength) and glycoproteins (repel proteins)
- Negatively charged glycoproteins repel filtered proteins
- Only ~1% of filtered albumin passes through
3. Inner layer of Bowman’s capsule
- Made of podocytes
- Podocytes form filtration slits allowing fluid to pass into Bowman’s capsule
92
What are podocytes?
These are cells that wrap around the capillaries of the glomerulus.
93
What are the main forces involved in glomerular filtration?
1. Glomerular capillary blood pressure (GCBP) – pushes water and solutes out of capillaries into Bowman’s capsule
2. Plasma-colloid oncotic pressure (π) – pulls water back into capillaries due to plasma proteins
3. Bowman’s capsule hydrostatic pressure (BCHP) – resists filtration, pushing against capillary outflow
94
What is the glomerular capillary blood pressure?
- ~55 mmHg (vs. 18 mmHg in regular capillaries)
- High pressure due to afferent arteriole being wider than efferent arteriole → increases resistance and maintains filtration along capillary length
95
What is plasma-colloid oncotic pressure?
- ~30 mmHg
- Caused by large plasma proteins that cannot cross the glomerular membrane
- Opposes filtration into Bowman’s capsule
96
What is Bowman’s capsule hydrostatic pressure?
- ~15 mmHg
- Pressure of fluid in Bowman’s capsule
- Resists movement of water out of glomerular capillaries
97
How is net filtration pressure (NFP) calculated?
NFP=GCBP−(plasma-colloid oncotic pressure+BCHP)
NFP=55−(30+15)=10 mmHg
Positive NFP → net movement of fluid into Bowman’s capsule
98
What factors determine glomerular filtration rate (GFR)?
GFR depends on:
- Filtration pressure
- Glomerular surface area
- Membrane permeability
These are collectively called the filtration coefficient (Kf).
99
What is the relationship between GFR, filtration coefficient, and filtration pressure?
GFR= Kf × Filtration Pressure
100
What are normal GFR values?
Males: ~125 mL/min
Females: ~115 mL/min
101
Which pressures are usually constant in GFR regulation?
- Plasma-colloid oncotic pressure
- Bowman’s capsule hydrostatic pressure
These typically remain stable but can change in pathological conditions.
102
How can a kidney stone affect GFR?
- A kidney stone obstructing the ureter increases Bowman’s capsule hydrostatic pressure
- This reduces GFR
103
How can dehydration (e.g., from severe diarrhea) affect GFR?
- Decreased plasma volume → lower blood pressure
- Increased plasma-colloid oncotic pressure
- Both effects decrease GFR
104
General concept—what decreases GFR?
Anything that:
- Decreases filtration pressure
- Increases opposing pressures (oncotic or Bowman’s capsule pressure)
- Reduces Kf (surface area/permeability)
105
What is the equation for net filtration pressure (NFP)?
NFP=Glomerular Capillary Blood Pressure−(Plasma-colloid Oncotic Pressure+Bowman’s Capsule Hydrostatic Pressure)
106
What is the equation for glomerular filtration rate (GFR)?
GFR= Kf × Net Filtration Pressure
107
Which pressure is primarily regulated to control GFR?
- Glomerular capillary blood pressure
- Changes in this pressure are directly proportional to changes in GFR
108
How does changing afferent arteriole diameter affect GFR?
Constriction (vasoconstriction): ↓ glomerular pressure → ↓ GFR
Dilation (vasodilation): ↑ glomerular pressure → ↑ GFR
109
Why are autoregulatory mechanisms important for GFR?
They prevent sudden fluctuations in GFR despite changes in blood pressure.
110
What are the two main autoregulatory (intrinsic) mechanisms?
1. Myogenic activity
2. Tubuloglomerular feedback (TGF)
111
What is myogenic activity?
A response of smooth muscle in afferent arterioles
Increased blood pressure → vessel stretches → constriction → ↓ GFR
Decreased blood pressure → dilation → ↑ GFR
112
What is tubuloglomerular feedback (TGF)?
- Involves the juxtaglomerular apparatus (JGA)
- Macula densa cells detect NaCl (salt) levels in tubular fluid
113
How does increased GFR affect tubuloglomerular feedback?
↑ GFR → ↑ flow & ↑ NaCl delivery to distal tubule
Macula densa releases ATP → converted to adenosine
Adenosine causes afferent arteriole constriction
Result: ↓ GFR
114
What happens when GFR is too low in TGF?
↓ NaCl delivery to macula densa
Leads to afferent arteriole dilation
Result: ↑ GFR
115
What is the overall goal of GFR autoregulation?
To maintain a stable GFR by adjusting afferent arteriole diameter in response to pressure and tubular fluid changes.
116
What happens to glomerular capillary pressure, net filtration pressure, and GFR during vasoconstriction of the afferent arteriole?
All decrease. Vasoconstriction reduces blood flow into the glomerulus → lowers glomerular capillary pressure → lowers net filtration pressure → lowers GFR.
117
What happens to glomerular capillary pressure, net filtration pressure, and GFR during vasodilation of the afferent arteriole?
All increase. Vasodilation increases blood flow into the glomerulus → raises glomerular capillary pressure → raises net filtration pressure → raises GFR.
118
Why do changes in glomerular capillary pressure directly affect GFR?
Because net filtration pressure depends mainly on glomerular capillary pressure (other pressures are relatively constant), and GFR is proportional to net filtration pressure.
119
How does the sympathetic nervous system affect GFR during events like hemorrhage?
It causes vasoconstriction of the afferent arteriole → decreases glomerular capillary pressure → decreases GFR → reduces urine output to conserve fluid.
120
What are baroreceptors and what is their role in kidney function?
Baroreceptors are mechanoreceptors that detect changes in blood pressure and trigger responses (including sympathetic activation) to restore pressure.
121
How much plasma is filtered by the kidneys, and what does this imply about renal blood flow?
About 20% of plasma is filtered. If GFR ≈ 125 mL/min, total renal blood flow ≈ 625 mL/min (plasma), or ~1140 mL/min of whole blood.
122
What proportion of cardiac output goes to the kidneys, and why is it so high?
About 22% of cardiac output. This high flow is needed for filtration and regulation of fluid volume, electrolytes, and waste removal—not just oxygen delivery.
123
Why is high renal blood flow functionally important?
It allows the kidneys to efficiently filter blood, regulate fluid and electrolyte balance, and remove metabolic wastes.
124
What are the sequential actions of the body in response to decreased arterial blood pressure?
1. ↓ Arterial Blood Pressure
2. Detection by aortic arch and carotid sinus baroreceptors
3. Increase in Sympathetic Activity
4. Generalized Arteriolar Vasoconstriction
5. Afferent Arteriolar Vasoconstriction
6. Decrease in Glomerular Capillary Blood Pressure
7. ↓ GFR
8. ↓ Urine Volume
9. Increase in Conservation of Fluid and Salt
10. ↑ Arterial Blood Pressure
125
How does glomerular filtrate compare to plasma?
Glomerular filtrate is identical to plasma except it does not contain plasma proteins.
126
Is glomerular filtration selective?
No, glomerular filtration is non-selective (except for proteins).
127
What is tubular reabsorption?
The process by which water and necessary solutes are returned from the filtrate to the plasma, while wastes remain in the filtrate.
128
What are the two steps of tubular reabsorption?
1. Movement (active or passive) from the tubule to the interstitial space
2. Passive movement from interstitial space to the bloodstream
129
How does tubular reabsorption differ from glomerular filtration?
Tubular reabsorption is highly selective and variable, unlike non-selective filtration.
130
What determines whether a substance is reabsorbed?
The body’s need for the substance (needed = high reabsorption, waste = low reabsorption).
131
What is the general trend for reabsorption of essential vs waste substances?
Essential substances → highly reabsorbed
Waste products → poorly reabsorbed or excreted
132
What is the reabsorption trend for key substances?
Water → very high (~99%)
Sodium → very high (~99.5%)
Glucose → complete (100%)
Urea → partial (~50%)
Phenol → none (0%)
133
Why are water and key solutes highly reabsorbed?
Because they are essential for maintaining homeostasis.
134
What are the luminal and basolateral membranes in kidney tubule cells?
Luminal membrane: faces the tubule lumen
Basolateral membrane: faces the interstitial fluid
135
What is transepithelial (transcellular) transport?
Movement of solutes across an epithelial cell layer through the cell.
136
Why must substances pass through epithelial cells instead of between them?
Because cells are connected by tight junctions, preventing movement between cells (except limited paracellular flow).
137
What are the 5 steps of transepithelial transport?
1. Cross luminal membrane
2. Move through cytosol
3. Cross basolateral membrane
4. Diffuse through interstitial fluid
5. Cross capillary wall into plasma
138
Can transepithelial transport be passive or active?
Yes, it can be either passive or active depending on the substance and step.
139
Why is Na⁺ reabsorption especially important?
Because it drives the reabsorption of many other substances and is highly regulated.
140
Where is Na⁺ reabsorbed in the nephron and in what proportions?
Proximal tubule → ~76%
Loop of Henle (ascending limb) → ~25%
Distal + collecting tubules → ~8%
141
What is the role of Na⁺ reabsorption in the proximal tubule?
Enables reabsorption of glucose, amino acids, water, Cl⁻, and urea.
142
What is the role of Na⁺ in the ascending limb of the loop of Henle?
Helps concentrate or dilute urine depending on body needs.
143
What happens in the distal and collecting tubules regarding Na⁺?
Na⁺ reabsorption is hormonally regulated
Important for ECF volume regulation and K⁺/H⁺ secretion
144
How is Na⁺ transported across tubule cells?
Luminal membrane → passive transport
Basolateral membrane → active transport via Na⁺-K⁺ ATPase pump
145
Why is the Na⁺-K⁺ ATPase pump important?
It keeps intracellular Na⁺ low, allowing passive Na⁺ entry from the lumen.
146
How much of the kidney’s energy is used for Na⁺ transport?
About 80%.
147
How does Na⁺ enter cells in the proximal tubule?
Via cotransport with nutrients (e.g., glucose, amino acids) using secondary active transport.
148
What is secondary active transport in this context?
Nutrients move against their gradient using the Na⁺ gradient created by the Na⁺-K⁺ ATPase pump.
149
How does Na⁺ enter cells in the collecting duct?
Through passive Na⁺ channels.
150
What are the fundamental steps of transepithelial transport (for a substance moving from the tubular membrane to the peritubular capillary)?
1. The substance must cross the luminal membrane
2. The substance must pass through the cytosol
3. The substance must cross the basolateral membrane
4. It must diffuse through the interstitial fluid
5. It must cross the capillary wall to enter the plasma
151
How is Na⁺ reabsorption different along the nephron?
Proximal tubule & loop of Henle → constant % reabsorbed (not regulated)
Distal tubule → small % reabsorbed under hormonal control
152
What is the main hormonal system regulating Na⁺?
The renin-angiotensin-aldosterone system (RAAS).
153
Where is renin produced?
By granular cells in the juxtaglomerular apparatus.
154
What are the three triggers for renin release?
1. Decreased blood pressure
2. Increased sympathetic activity
3. Decreased Na⁺ detected by macula densa
155
What is the first step of the RAAS pathway?
Renin converts angiotensinogen (from the liver) into angiotensin I.
156
What does ACE do in RAAS?
Converts angiotensin I into angiotensin II (mainly in the lungs).
157
What does angiotensin II do?
Stimulates the adrenal cortex to release aldosterone.
158
What is the role of aldosterone?
Increases Na⁺ reabsorption in the distal and collecting tubules.
159
How does aldosterone increase Na⁺ reabsorption?
Increases Na⁺ channels in luminal membrane
Increases Na⁺-K⁺ ATPase pumps in basolateral membrane
160
What is the overall effect of aldosterone on the body?
↑ Na⁺ retention
↑ Water retention (water follows Na⁺)
↑ Blood pressure
161
What is ANP and when is it released?
Atrial natriuretic peptide; released when blood volume/venous return increases (atrial stretch).
162
What are the three main actions of ANP?
1. Inhibits Na⁺ reabsorption (↑ Na⁺ excretion)
2. Inhibits renin and aldosterone
3. Dilates afferent arterioles → ↑ GFR
163
What is the overall effect of ANP?
Decreases blood volume and blood pressure (opposes RAAS).
164
What is the transport maximum (Tm)?
The maximum rate at which a substance can be reabsorbed due to limited carrier proteins.
165
What happens if a substance exceeds its Tm?
The excess is excreted in the urine.
166
What is the renal threshold?
The plasma concentration at which the Tm is exceeded and the substance begins appearing in urine.
167
Why is tubular reabsorption limited for some substances?
Because carrier proteins are finite in number.
168
Are all substances regulated by Tm in the same way?
No:
Some (e.g., phosphate) → plasma levels regulated by kidneys
Others (e.g., glucose) → have a Tm but are not regulated by kidneys
169
What is angiotensinogen?
A protein made in the liver that is present at high concentrations in the plasma
170
How do the kidneys regulate plasma concentrations of electrolytes like phosphate?
By adjusting reabsorption and excretion based on renal thresholds and hormonal control.
171
Why is phosphate a good example of kidney regulation?
Because its renal threshold is equal to its normal plasma concentration.
172
What happens to phosphate levels after eating?
- Plasma phosphate increases
- Filtered load increases
- Excess phosphate (above threshold) is excreted in urine
173
How does this process restore phosphate levels?
By excreting excess phosphate, plasma levels return to normal.
174
How does phosphate reabsorption differ from glucose reabsorption?
Phosphate → hormonally regulated
Glucose → not hormonally regulated (depends on Tm only)
175
Which hormones regulate phosphate and calcium reabsorption?
Primarily parathyroid hormone (PTH).
176
What happens when plasma phosphate levels fall?
Two mechanisms act to restore levels.
177
What is the first response to low phosphate levels?
↓ Phosphate → ↑ calcium (inverse relationship)
↑ Calcium suppresses PTH
↓ PTH → ↑ phosphate reabsorption in kidneys
178
What is the second response to low phosphate levels?
↑ Activation of vitamin D in the kidneys
↑ Intestinal absorption of phosphate
179
What is the overall effect of these responses?
Restoration of plasma phosphate concentration to normal.
180
Is glucose regulated by the kidneys?
No, glucose plasma concentration is not regulated by the kidneys.
181
What is the normal plasma concentration of glucose?
100 mg per 100 mL of plasma.
182
Is glucose filtered in the kidney?
Yes, it is freely filterable, so filtrate concentration equals plasma concentration.
183
What is the formula for filtered load?
Filtered load = plasma concentration × GFR
184
What is the filtered load of glucose under normal conditions?
100 mg/100 mL × 125 mL/min = 125 mg/min
185
What happens to filtered load if GFR increases?
Filtered load increases proportionally.
186
What determines how much glucose is reabsorbed?
Its transport maximum (Tm), due to limited carrier proteins.
187
At what plasma concentration will glucose start appearing in the urine?
In the case of glucose, its normal Tm is 375 mg/min. This means that for all filtered loads of glucose below 375 mg/min, 100% of the glucose will be reabsorbed. Only when the filtered load of glucose exceeds 375 mg/min will glucose appear in the urine.
188
Diabetes mellitus causes increased glucose levels in the blood. This, in turn, can cause increased levels of glucose in the urine. Why this increase in glucose in the urine exists?
Ordinarily, urine contains no glucose because the kidneys are able to reabsorb it all. Bowman’s capsule collects the filtrate that the glomerulus forms which includes urea, electrolytes, and glucose. The filtrate then passes into the proximal tubule to be reabsorbed. Proximal tubule, however, can only reabsorb a limited amount of glucose. When blood glucose levels exceed about 300 mg/100 mL, the proximal tubule is overwhelmed and begins to excrete glucose into the urine.
189
How is glucose and amino acid reabsorption linked to Na⁺ transport?
They are reabsorbed via secondary active transport, driven by the Na⁺ gradient created by the Na⁺-K⁺ ATPase pump.
190
Which other substances depend on Na⁺ reabsorption?
Chloride (Cl⁻)
Water
Urea
191
How is water reabsorbed in the nephron?
Passively, by osmosis, following Na⁺ reabsorption.
192
What percentage of water is reabsorbed in each segment?
Proximal tubule → 65% (~117 L/day)
Loop of Henle → 15%
Distal + collecting tubules → 20%
193
Is water reabsorption constant throughout the nephron?
Proximal tubule & loop → constant
Distal & collecting tubules → variable (hormone-dependent)
194
What regulates water reabsorption in the distal nephron?
Hormones (especially vasopressin) and hydration state.
195
What are aquaporins?
Water channels that allow water to move across membranes.
196
How do aquaporins differ along the nephron?
Proximal tubule → always open
Distal tubule → regulated by vasopressin
197
What forces drive water reabsorption into peritubular capillaries?
Osmotic gradient from Na⁺
Plasma-colloid oncotic pressure
198
Do the kidneys directly regulate chloride?
No
199
How is chloride reabsorbed?
- Mainly paracellularly (between cells)
- Down its electrochemical gradient
200
What determines how much chloride is reabsorbed?
The amount of Na⁺ reabsorbed.
201
Is urea reabsorbed or excreted?
Both — a significant amount is reabsorbed despite being a waste product.
202
Why is there no net urea diffusion at the start of the proximal tubule?
Because tubular and plasma urea concentrations are equal.
203
Why does urea become reabsorbed later in the proximal tubule?
Water reabsorption reduces volume (~2/3)
Urea concentration increases ~3×
This creates a gradient for passive reabsorption
204
How much urea is ultimately excreted?
About 40–50% of filtered urea is excreted.
205
What is BUN (blood urea nitrogen)?
A clinical measure of urea levels in blood.
206
Why is BUN clinically important?
- Indicates kidney function
- ↑ BUN = reduced urea excretion → possible renal failure
207
What is tubular secretion?
Movement of substances from the peritubular capillaries → tubule lumen via transepithelial transport.
208
How is tubular secretion different from tubular reabsorption?
Reabsorption → tubule → blood
Secretion → blood → tubule
209
Why is tubular secretion important?
It provides an additional pathway (besides filtration) to eliminate substances from the body.
210
What are the main substances secreted?
- Hydrogen ions (H⁺)
- Potassium ions (K⁺)
- Organic anions and cations (many are foreign substances)
211
Where are H⁺ ions secreted in the nephron?
- Proximal tubule
- Distal tubule
- Collecting tubule
212
What determines the amount of H⁺ secretion?
The acidity of the plasma.
213
How does plasma H⁺ concentration affect secretion?
High H⁺ → ↑ secretion
Low H⁺ → ↓ secretion
214
What is the role of H⁺ secretion?
Regulation of acid–base balance.
215
Does potassium undergo reabsorption or secretion?
Both
216
What happens to K⁺ in the proximal tubule?
- Freely filtered
- Actively reabsorbed (mostly unregulated)
217
Where is K⁺ secretion regulated?
Distal and collecting tubules.
218
What controls K⁺ secretion?
Plasma K⁺ levels.
219
How do plasma K⁺ levels affect secretion?
High K⁺ → ↑ secretion
Low K⁺ → ↓ secretion
220
How are the kidneys involved in K⁺ balance?
By adjusting secretion to regulate plasma K⁺ levels.
221
What mechanism drives K⁺ secretion?
Active transport via the Na⁺-K⁺ ATPase pump.
222
How does Na⁺ transport contribute to K⁺ secretion?
- Na⁺ pumped out of cell (basolateral side)
- K⁺ pumped into cell → builds high intracellular K⁺
- K⁺ then diffuses into tubule lumen via channels
223
Why does K⁺ move into the tubular fluid?
It follows its concentration gradient through K⁺ channels in the luminal membrane.
224
How does tubular secretion complement filtration?
It allows elimination of substances that were not filtered or insufficiently filtered.
225
Why isn’t K⁺ secreted in all segments where Na⁺ is reabsorbed?
Because K⁺ secretion depends on the location of K⁺ channels, not just the Na⁺-K⁺ ATPase pump.
226
Where does K⁺ secretion primarily occur in the nephron?
In the distal tubule and collecting tubule.
227
What is special about K⁺ channels in the distal and collecting tubules?
They are located in the luminal membrane, allowing K⁺ to diffuse into the tubule lumen.
228
How does K⁺ get into the tubular lumen in these segments?
- Na⁺-K⁺ ATPase pumps K⁺ into the cell
- K⁺ then diffuses through luminal K⁺ channels into the lumen
229
What happens to K⁺ in earlier nephron segments (e.g., proximal tubule)?
It is not secreted despite Na⁺ reabsorption.
230
Why is K⁺ not secreted in these earlier segments?
Because K⁺ channels are mainly in the basolateral membrane, not the luminal side.
231
What is the consequence of basolateral K⁺ channels?
K⁺ pumped into the cell diffuses back into the interstitial fluid, not into the tubule.
232
What is meant by “K⁺ recycling”?
K⁺ moves into the cell via the Na⁺-K⁺ pump and then returns to the interstitial space, rather than being secreted.
233
Why is K⁺ recycling important?
It allows the Na⁺-K⁺ ATPase pump to continue functioning efficiently for Na⁺ reabsorption.
234
What is the net effect of K⁺ movement in proximal segments?
No net K⁺ secretion occurs.
235
What determines whether K⁺ is secreted or recycled?
The membrane location of K⁺ channels (luminal vs. basolateral)
236
What are the main factors that alter K⁺ secretion?
- Plasma K⁺ levels
- Na⁺ balance and aldosterone
- Acid–base status (H⁺ levels)
237
How does an increase in plasma K⁺ affect K⁺ secretion?
It directly stimulates aldosterone release, increasing K⁺ secretion.
238
How does aldosterone influence K⁺ secretion?
↑ Na⁺ reabsorption
↑ K⁺ secretion (linked via Na⁺-K⁺ ATPase)
239
Why are Na⁺ reabsorption and K⁺ secretion linked?
Because both depend on the Na⁺-K⁺ ATPase pump.
240
What conditions can indirectly increase K⁺ secretion?
↓ Plasma Na⁺
↓ ECF volume
↓ Blood pressure
241
What is a potential consequence of excessive K⁺ secretion?
K⁺ depletion (hypokalemia).
242
How does acid–base status affect K⁺ secretion?
Through competition between H⁺ and K⁺ for transport.
243
What happens during acidosis (high H⁺)?
H⁺ enters epithelial cells
H⁺ is secreted into tubule
↓ K⁺ secretion
244
Why does K⁺ secretion decrease during acidosis?
Na⁺-K⁺ ATPase can substitute H⁺ for K⁺
Limited pumps → more H⁺ transport = less K⁺ transport
245
What is the consequence of reduced K⁺ secretion in acidosis?
Elevated plasma K⁺ levels (hyperkalemia).
246
What types of carriers exist in the proximal tubule for secretion?
Organic anion carriers
Organic cation carriers
247
What are the three main functions of organic ion secretion?
1. Increase excretion
2. Excrete poorly soluble substances
3. Remove foreign compounds
248
How does tubular secretion increase excretion?
By adding substances to tubular fluid beyond what was filtered.
249
Why is this important for signaling molecules?
Helps remove substances like:
- Norepinephrine
- Histamine
- Prostaglandins
→ limiting their biological effects
250
Why can’t many organic ions be filtered easily?
They are hydrophobic and bound to plasma proteins.
251
How does secretion help remove protein-bound substances?
- Only free fraction is filtered
- Secretion removes free fraction
- This causes more to detach from proteins → enhances excretion
252
What types of foreign substances are secreted?
Drugs
Food additives
Pesticides
Environmental pollutants
253
Do kidneys regulate secretion of foreign compounds?
No—there are no regulatory mechanisms to increase their removal if needed.
254
T or F: In the proximal tubule, roughly 67% of Na+ is actively reabsorbed.
True
255
T or F: No filtered glucose is reabsorbed within the proximal tubule.
False
256
T or F: All H2O is reabsorbed within the distal tubule and collecting duct.
False
257
T or F: There are variable amounts of PO43- reabsorbed within the proximal tubule.
True
258
What is the normal glomerular filtration rate (GFR)?
125 mL/min
259
How much filtrate is reabsorbed?
About 124 mL/min.
260
What is the final urine output?
~1 mL/min
~1.5 L/day
261
What happens to solutes during this reduction in volume?
They become concentrated in the urine.
262
What is plasma clearance?
The volume of plasma cleared of a substance per minute by the kidneys.
263
What does plasma clearance measure?
The efficiency of the kidneys in removing a substance.
264
What are the units of plasma clearance?
Volume (mL/min), not amount of substance.
265
What is the formula for plasma clearance?
Clearance = (Urine concentration × Urine flow rate) / Plasma concentration
266
What are the three categories of substances based on clearance?
1. Filtered, not reabsorbed
2. Filtered and reabsorbed
3. Filtered and secreted, not reabsorbed
267
What is a classic example of filtered, not reabsorbed?
Inulin
268
Why is inulin useful?
- Freely filtered
- Not reabsorbed or secreted
→ Clearance = GFR
269
What is the clearance of inulin?
125 mL/min (equal to GFR).
270
Why is inulin not commonly used clinically?
It must be continuously infused to maintain steady levels.
271
What is used clinically instead of inulin?
Creatinine
272
Why is creatinine useful?
- End product of muscle metabolism
- Relatively constant plasma levels
- Not reabsorbed (minor secretion)
273
How does reabsorption affect clearance (for filtered and reabsorbed)?
Clearance is less than GFR.
274
What is the clearance of glucose?
0 mL/min (normally fully reabsorbed).
275
What is the clearance of urea?
~62.5 mL/min (about 50% reabsorbed).
276
Why is urea clearance less than GFR (for filtered and reabsorbed)?
Because a portion is reabsorbed.
277
How does secretion affect clearance (for filtered and secreted)?
Clearance is greater than GFR.
278
Why is clearance greater than GFR in case of filtered and secreted?
Because substance is added to tubule via secretion.
279
What is an example for filtered and secreted?
Hydrogen ions (H+)
280
What is the example clearance of H⁺?
~150 mL/min (greater than GFR of 125 mL/min).
281
How does clearance compare to GFR in each case?
Equal to GFR → filtered only (e.g., inulin)
Less than GFR → reabsorbed (e.g., glucose, urea)
Greater than GFR → secreted (e.g., H⁺)
282
What does comparing clearance to GFR tell you?
How the kidney handles a substance (reabsorbed, secreted, or neither).
283
Select whether the molecules are secreted and/or reabsorbed: Hydrogen ions
Secreted
284
Select whether the molecules are secreted and/or reabsorbed: Glucose
Reabsorbed
285
Select whether the molecules are secreted and/or reabsorbed: Urea
Reabsorbed
286
Select whether the molecules are secreted and/or reabsorbed: Inulin
Neither
287
What is the main goal of kidney water handling?
To produce urine with varying concentrations depending on the body’s hydration state.
288
What fundamental principle allows urine to be concentrated?
Osmosis
289
What determines ECF osmolarity?
The ratio of water to solute.
290
Does this principle apply to tubular fluid?
Yes, tubular fluid osmolarity also depends on water vs solute content.
291
Why is concentrating urine conceptually challenging?
Because concentrated urine would normally draw water out of surrounding tissues by osmosis.
292
How do the kidneys overcome this challenge?
By creating a vertical osmotic gradient in the medulla.
293
What is the osmolarity of normal ECF?
~300 mOsm/L.
294
What is the osmolarity in the renal cortex?
~300 mOsm/L (same as normal ECF).
295
How does osmolarity change in the medulla?
It increases progressively from cortex to renal pelvis.
296
What is the osmolarity range in the medulla?
From 300 mOsm/L → 1200 mOsm/L.
297
What is this increasing gradient called?
The vertical osmotic gradient.
298
Why is the medullary osmotic gradient important?
It allows water to be reabsorbed from the tubules, concentrating urine.
299
What range of urine osmolarity can the kidneys produce?
Dilute urine → ~100 mOsm/L
Concentrated urine → up to ~1200 mOsm/L
300
What determines whether urine is dilute or concentrated?
The hydration state of the body.
301
What is the key requirement for producing concentrated urine?
A hyperosmotic medullary interstitium.
302
What are the structural differences of these two different types of nephrons, specifically with reference to the Loop of Henle?
Cortical: The loop of Henle only dips slightly into the medulla.
Juxtamedullary: The loop of Henle dips all the way down to the renal pelvis. The vasa recta of these nephrons also goes all the way to the renal pelvis. Flow in the loop of Henle and the vasa recta goes in opposite directions in what is called countercurrent flow.
In both types of nephrons, the descending collecting ducts that go all the way to the renal pelvis. These anatomical arrangements, coupled with the permeability and transport properties of the different sections of the tubule, are what allow the kidneys to make urine of different concentrations. The loops of Henle establish the vertical osmotic gradient, the vasa recta preserve the gradient, and the collecting ducts use the gradient, along with vasopressin, to produce urine of varying concentrations. Collectively, this is known as the medullary countercurrent system.
303
How is vertical osmotic gradient established if we follow the flow of filtrate through a juxtaglomerular (long loop) nephron?
1. As soon as the fluid leaves Bowman’s capsule and enters the proximal tubule, there is a strong drive for osmotic reabsorption of water secondary to the active reabsorption of Na+. Remember, water follows Na+.
2. By the end of the proximal tubule, due to Na+ reabsorption, 65% of the filtrate volume has been reabsorbed. What is important to note, however, is that the osmolarity of the tubular fluid at this point is 300 mOsm/L, or isotonic, to other bodily fluids.
3. In the loop of Henle, an additional 15% of the filtered water will be reabsorbed during the establishment and maintenance of the vertical osmotic gradient. The descending and ascending limbs of the loop of Henle are distinct in their function. Ascending limbs are impermeable to water, but reabsorb Na+. In this case, water does not follow Na+. The descending limbs, however, are highly permeable to water, but do not reabsorb Na+.
304
What are the step-by-step processes that establish the vertical osmotic gradient in the loop of Henle?
1. Initial state (no gradient):
- Filtrate enters descending limb at 300 mOsm/L
- Interstitial fluid is 300 mOsm/L
- Descending limb is permeable to both Na⁺ and water
- → No net movement (isotonic equilibrium)
2. Na+ pumping in ascending limb:
- Ascending limb actively reabsorbs Na⁺ (no water follows)
- Interstitial fluid becomes more concentrated (~400 mOsm/L)
- Ascending limb fluid becomes dilute (~200 mOsm/L)
- → A ~200 mOsm gradient is created
- Descending limb equilibrates → becomes ~400 mOsm/L
3. Fluid shift with new filtrate:
- New 300 mOsm/L fluid enters descending limb
- Existing fluid is pushed deeper into medulla
- More concentrated fluid (400 mOsm/L) moves into ascending limb
- Na⁺ is again pumped out → gradient re-established
- Note: gradient may temporarily exceed ~200 mOsm during shifting
4. Re-equilibration across limbs:
- Ascending limb continues pumping Na⁺ out
- Water leaves descending limb (osmosis)
- At each horizontal level:
-- Descending limb equilibrates with interstitium (more concentrated)
-- Ascending limb remains more dilute
- → ~200 mOsm difference restored at each level
5. Continuous flow disrupts and rebuilds gradient:
- New 300 mOsm/L filtrate keeps entering
- Fluid shifts forward again
- Gradient is temporarily disrupted
- Then re-established through Na⁺ pumping + water movement
6. Repeated cycles amplify gradient:
- Each cycle increases medullary osmolarity
- Descending limb becomes progressively more concentrated
- Ascending limb becomes progressively more dilute
7. Final steady-state gradient:
- Interstitial osmolarity: 300 → 1200 mOsm/L
- Descending limb (deep): ~1200 mOsm/L
- Ascending limb (to distal tubule): ~100 mOsm/L
- → Max = 4× normal osmolarity
- → Outflow = ~1/3 normal osmolarity
8. Maintenance of gradient:
- Continuous filtrate flow
- Ongoing Na⁺ reabsorption (ascending limb)
- Ongoing water movement (descending limb)
- → Gradient remains stable once established
305
How is the medullary osmotic gradient established?
1. Start isotonic: 300 mOsm in tubule and interstitium → no movement
2. Ascending limb pumps out Na⁺ → interstitium ↑ (400), tubule ↓ (200)
3. Descending limb loses water → equilibrates with interstitium (400)
4. New filtrate enters → fluid shifts forward → gradient disrupted then reformed
5. Repeated cycles: Na⁺ out (ascending) + water out (descending)
6. Gradient multiplies down medulla → 300 → 1200 mOsm
7. Final:
Descending deep = 1200 mOsm
Ascending out = 100 mOsm
8. Maintained by continuous flow + transport
306
How is the medullary osmotic gradient established?
Pump Na⁺ out, water follows in descending, flow shifts, repeat → gradient builds to 1200.
307
Order the steps of countercurrent multiplication in the loop of Henle.
1. 200 m O s m /L gradient is first established between the interstitial fluid and the ascending limb
2. Fluid flows forward several frames
3. Ascending and descending limbs reestablish the 200 mOsm/L gradient
4. Fluid flows forward several frames again
5. 200 m O s m /L gradient is established once again at each horizontal level
6. Vertical osmotic gradient is established and maintained in an ongoing fashion
308
Why does countercurrent multiplication seem pointless at first, and what is its actual purpose?
Seems pointless because:
- Fluid enters loop isotonic (300 mOsm/L)
- Becomes more concentrated in descending limb
- Then becomes more dilute in ascending limb
Actual purposes:
1. Establishes a vertical osmotic gradient in the medulla (300 → 1200 mOsm/L)
2. Allows collecting ducts to produce:
- More concentrated urine
- More dilute urine than body fluids
3. Reduces urine volume, conserving water and salt
309
When is vasopressin released and inhibited?
Released when:
- Water deficit
- ECF is hypertonic
Inhibited when:
- ECF is hypotonic
Source: Posterior pituitary gland
310
How does vasopressin increase water reabsorption?
1. Travels in blood to kidneys
2. Acts on distal tubule & collecting duct cells
3. Increases aquaporin insertion in luminal membrane
4. Water enters epithelial cells
5. Water passively moves to interstitial fluid → plasma
Important:
- No effect on proximal tubule or loop of Henle
- Only affects distal + collecting tubules
311
Where does vasopressin act compared to total water reabsorption in the nephron?
- ~80% of water reabsorbed before distal tubule (proximal + loop)
- Vasopressin only affects the remaining portion
- Therefore: controls final urine concentration
312
What osmotic conditions drive water movement in the distal nephron?
- Tubular fluid entering distal tubule: ~100 mOsm/L
- Interstitial fluid:
Cortex: ~300 mOsm/L
Medulla: up to 1200 mOsm/L
- → Strong osmotic gradient pulls water out of tubule
- BUT: water only moves if vasopressin is present
313
What happens under maximum vasopressin (water deficit)?
↑ Aquaporins in distal + collecting tubules
↑ Water reabsorption
Tubular fluid equilibrates with interstitium
Results:
- Urine osmolarity: up to 1200 mOsm/L (maximum)
- Urine flow: as low as 0.3 mL/min
- → Highly concentrated, low-volume urine
314
What happens when vasopressin is suppressed (water excess)?
- ECF becomes hypotonic (<300 mOsm/L)
- No aquaporin insertion
- No water reabsorption in distal/collecting tubules
Results:
- Urine osmolarity: ~100 mOsm/L (very dilute)
- Urine flow: up to 25 mL/min
- → Large volume, dilute urine
315
How do countercurrent multiplication and vasopressin work together?
Countercurrent multiplication:
→ Creates medullary osmotic gradient (300–1200 mOsm/L)
Vasopressin:
→ Determines whether water can leave tubules
Together:
→ Allow kidneys to produce urine from very dilute (100 mOsm/L) to very concentrated (1200 mOsm/L)
316
The vertical osmotic gradient allows for the production of both more concentrated and more dilute urine than normal bodily fluids. How is this possible?
- Ascending loop of Henle: actively reabsorbs Na⁺ but is impermeable to water → tubular fluid becomes hypotonic. This ensures fluid entering distal tubules is always dilute, regardless of hydration.
- Medullary osmotic gradient: established by the loop of Henle (vertical gradient 300 → 1200 mOsm/L) provides the osmotic driving force for water reabsorption in the distal and collecting tubules.
- Vasopressin (ADH): released in response to dehydration → inserts aquaporins in distal/collecting tubules → water reabsorbed into hypertonic medulla → tubular fluid becomes concentrated.
- Without vasopressin: no water reabsorption → hypotonic urine (~100 mOsm/L) excreted.
- With maximal vasopressin: water reabsorption maximized → concentrated urine (~1200 mOsm/L).
- Integration: Loop of Henle dilutes and establishes the gradient; distal/collecting tubules adjust water reabsorption based on vasopressin → allows kidney to produce urine ranging from very dilute to very concentrated while conserving water and salt.
317
What is the role of the vasa recta in the kidney?
It supplies blood to the renal medulla and supports the countercurrent multiplier mechanism.
318
Why is the vasa recta closely associated with the loops of Henle?
Because of its hairpin shape, which allows it to dive down into the medulla, aligning with the descending and ascending loops of Henle.
319
What are the permeability characteristics of the vasa recta?
Highly permeable to NaCl and H2O.
320
What does “countercurrent” mean in the context of the vasa recta?
Blood flow through the vasa recta is opposite to the flow of fluid through the loop of Henle.
321
What is the approximate osmolarity of interstitial fluid in the renal medulla where the vasa recta travel?
1200 mOsm/L.
322
How does the high osmolarity of the medulla affect the composition of blood in the vasa recta?
Blood osmolarity changes as solutes and water are passively exchanged to remain isotonic with the surrounding interstitial fluid.
323
What is countercurrent exchange?
The passive exchange of solutes and water between the vasa recta and the interstitial fluid that preserves the medullary hypertonic gradient.
324
How does countercurrent exchange differ from countercurrent multiplication?
In countercurrent exchange, flow does not establish the osmotic gradient; it simply preserves it, whereas countercurrent multiplication establishes the gradient in the loop of Henle.
325
What is the osmolarity of blood in the vasa recta as it leaves the renal cortex?
300 mOsm/L (isotonic to the cortical interstitial fluid).
326
How does blood osmolarity change in the descending limb of the vasa recta?
Plasma remains isotonic with the surrounding interstitial fluid by reabsorbing Na+ and water leaving.
327
What is the plasma osmolarity at the bottom of the vasa recta loop in the medulla?
1200 mOsm/L.
328
How does the ascending limb of the vasa recta maintain isotonicity with the medulla?
Water is reabsorbed and Na+ leaves, keeping plasma isotonic with the surrounding interstitial fluid.
329
What is the osmolarity of blood in the vasa recta as it re-enters the cortex?
300 mOsm/L, isotonic to the cortical interstitial fluid.
330
What is the difference between water reabsorption that follows solute reabsorption and water reabsorption that is independent of solute reabsorption?
In segments permeable to water, water reabsorption always follows solute reabsorption due to osmosis, whereas water reabsorption can also occur independently when solute excretion or hormone effects change water handling.
331
What happens when excess, un-reabsorbed solute is present in the tubular fluid?
It exerts an osmotic influence to retain water in the tubule, increasing urine output—a phenomenon called osmotic diuresis.
332
What is osmotic diuresis?
Increased excretion of both water and excess un-reabsorbed solute.
333
Give an example of osmotic diuresis in humans.
In diabetes, high glucose levels exceed reabsorption capacity, attracting water into the tubules and causing increased urine production.
334
What is water diuresis?
Increased excretion of water with little or no change in solute excretion.
335
How does alcohol consumption cause water diuresis?
Alcohol suppresses vasopressin secretion, leading to excretion of dilute urine in volumes greater than alcohol consumed, potentially causing dehydration.
336
How is urine transported from the kidneys to the bladder?
Urine is transmitted through the ureters by peristaltic contractions.
337
Can urine normally flow backward from the bladder to the kidneys?
No, backward flow is normally prevented unless enough pressure is generated.
338
What are the main structural features of the bladder?
Composed of smooth muscle, lined with specialized epithelium, capable of expansion, and highly innervated by the parasympathetic nervous system.
339
What role does the parasympathetic nervous system play in bladder function?
It stimulates bladder contraction.
340
What are the two sphincters guarding the urethral exit?
The internal urethral sphincter and the external urethral sphincter.
341
What is the internal urethral sphincter and how is it controlled?
Part of the bladder wall, under involuntary control, it closes the bladder outlet when the bladder is relaxed.
342
What is the external urethral sphincter and how is it controlled?
A skeletal muscle sphincter encircling the urethra, supported by the pelvic diaphragm, under voluntary control, preventing urination even during bladder contraction.
343
What is micturition?
The process of bladder emptying (urination).
344
What two mechanisms govern micturition?
The micturition reflex and voluntary control.
345
How does the micturition reflex work?
When bladder volume reaches 250–400 ml, stretch activates afferent fibers to the spinal cord, stimulating parasympathetic contraction of the bladder and relaxation of the external sphincter; the internal sphincter opens as the bladder contracts.
346
How is micturition reflex evident in infants?
Infants urinate automatically when the bladder fills enough to activate the reflex.
347
How does voluntary control override the micturition reflex?
Excitatory signals from the cerebral cortex can inhibit the reflex by sensing bladder filling before reflex activation.
348
Why can voluntary control of micturition only last for so long?
Continuous urine production eventually raises bladder pressure enough to activate the reflex, leading to involuntary emptying.
PHGY 216
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