Renal Physiology Flashcards
1
Q
What is the primary function of the kidneys?
A
Regulate the plasma of blood
ie Regulate our blood volume and pressure (through regulation of ECF (plasma, IF and CSF))
2
Q
What are five functions of the kidney?
A
- Regulate our blood volume and pressure
- Maintain [water] and fluid volume
- Maintain acid-base balance
- pH (measure of [H+] in a sol’n)
- Excretion of waste products
- urea, uric acid, creatinine, bilirubin
- foreign chemicals
- Synthesis of new glucose molecules gluconeogenesis
- Secrete renal hormones
- Erythropoietin (EPO) synthesized by fibroblasts in the kidney
- Renin
- 1,25-dihydroxyvitamin D
3
Q
Kidneys regulate fluid volume, which affects _______ and _________
A
Kidneys regulate fluid volume, which affects blood volume and blood pressure
4
Q
What is the distribution of water between ICF and ECF?
ECF includes _____, ______ and ______
A
- 60% of body weight is water
- 40% is intracellular fluid (ICF)
- 20% is Extracellular fluid (ECF)
- ECF includes Plasma, Interstitial Fluid (IF), and Cerebrospinal fluid (CSF)
5
Q
Fluid volume changes can occur during various health disorders:
- Changes that occur where plasma volume is affected happen due to:
A
Fluid volume changes can occur during various health disorders:
- Changes that occur where plasma volume is affected happen due to:
- rapid movement of water from plasma component by the process of osmosis
6
Q
Kidney’s regulate the ______ which includes: (3)
A
Kidney’s regulate the Extracellular fluid which includes: (3)
- Plasma
- Interstitial fluid
- cerebrospinal fluid
7
Q
Sodium and Chloride have a higher concentration in which fluid compartment (ICF or ECF)?
A
Sodium and Chloride have a higher concentration in Extracellular fluid
(Na+ is pumped out and Cl- follows)
Sodium
Out
Potassium
In
Positive
Out
Negative
In
8
Q
Potassium has a higher concentration in which fluid compartment?
A
Potassium has a higher concentration in Intracellular fluid (ICF)
9
Q
Bicarbonate has a higher concentration in which fluid compartment?
A
Bicarbonate has a higher concentration in extracellular fluid
(along with Sodium and Chloride)
10
Q
Phosphate has a higher concentration in which fluid compartment?
A
Phosphate has a higher concentration in intracellular fluid
(along with potassium)
11
Q
What are Aquaporins?
A
Specialized water-selective channels in the plasma membrane that are responsible for the rapid diffusion of water
12
Q
What is water concentration of a solution dependent on?
A
Number of solutes dissolved in the water
(High osmolarity = lots of dissolved solute = water moves toward high osmolarity)
13
Q
Water concentration is measured in:
Osmoles:
Osmolarity:
A
Water concentration is measured in:
Osmoles: 1 osmole (osm) = 1 mole of solute particles
Osmolarity: number of solutes per unit volume of sol’n expressed in moles/L
14
Q
Water concentration is always recorded in ______
A
Water concentration is always recorded in osmoles
15
Q
What is Osmosis defined as?
A
Net diffusion of water across a selectively permeable membrane from a region of high water concentration to one with lower water concentration
16
Q
The pressure necessary to prevent solvent movement (osmosis) is known as:
A
Osmotic pressure of the solution
17
Q
Define osmotic pressure
A
Pressure required to stop osmosis completely
- will push and prevent water from coming into the cell, to prevent them from taking in too much water and bursting
18
Q
What is tonicity?
A
Tonicity= concentration of non-penetrating solutes of an extracellular sol’n
-solutes that cannot cross the plasma membrane BUT may influence changes in cell volume
19
Q
- Tonicity is determined by:
- The concentrations of the non-penetrating solutes may influence ________
A
- Tonicity is determined by: The concentration of non-penetrating solutes of an extracellular solution relative to the intracellular environment
- The concentrations of the non-penetrating solutes may influence changes in cell volume
20
Q
What are the three classes of tonicity that one solution could have relative to another?
A
- Isotonic (isoosmotic)
- same osmolarity outside and inside the cell
- Hypertonic (Hyperosmotic)
- higher osmolarity outside than inside the cell (water moves out)
- Hypotonic (Hypoosmotic)
- Lower osmolarity outside than inside the cell (water moves in)
isoosmotic, hyperosmotic, and hypoosmotic refer to the osmolarity but do not take into consideration in the solute is non-penetrating or penetrating
21
Q
Water flows from a region of _____ osmolarity to a region of _____ osmolarity.
The normal osmolarity inside a cell is ~______
A
Water flows from a region of lower osmolarity to a region of higher osmolarity.
The normal osmolarity inside a cell is ~300mOsm/L (milliosmoles per liter)
22
Q
How does cell volume change when a cell is placed into an isotonic solution?
A
No net change in cell volume
23
Q
How does cell volume change when the cell is placed into a Hypertonic solution?
A
Hypertonic = ECF has higher osmolarity (higher [solute]) water will flow from inside the cell to outside and the cell will shrink
24
Q
How does cell volume change when a cell is placed into a hypotonic solution?
A
Hypotonic = the ECF has a LOWER osmolarity (lower [solute])
Water will move back into the cell and the cell will swell
25
ECF compartment = ______ (which stays within the blood vessels) and \_\_\_\_\_
ECF compartment = _Plasma_ (which stays within the blood vessels) and _interstitial fluid_
\*Kidney's can regulate the volume of the **plasma**
26
What is absorption?
Movement of water and solutes from the interstitial fluid compartment to the plasma
27
What is filtration?
Movement of water and solutes from the plasma to the interstitial fluid
28
Hydrostatic pressure is the pressure exerted by a \_\_\_\_
Hydrostatic pressure is the pressure exerted by a _fluid (_Every fluid has this property)
29
What is Capillary hydrostatic pressure?
Does it favour filtration or absorption?
Hydrostatic pressure exerted on the walls of the capillary by blood as it flows through the capillary
* Favours filtration
* ie pushes some of the fluid out of the capillary into the IF
30
What is Interstitial fluid hydrostatic pressure and does it favour filtration or absorption?
* Pressure of the IF on the walls of the capillary (PIF)
* Pushes fluid INTO the capillaries (ie favours absorption)
31
What is the contribution of the plasma proteins to fluid movement?
* Proteins are large and sometimes charged = cannot move in and out of capillaries easily
* Inside the plasma there is a high [plasma proteins] which contribute to **osmolarity**
* osmotic force due to plasma protein concentration (πC):
* ↑[p. proteins] = ↓[H2O] inside the capillaries
* Water will move **into** the capillary
32
How is the Net filtration pressure calculated?
With the Starling forces (PC, πC, πIF, PIF)
Net Filtration Pressure = PC + πIF - PIF - πC
Forces out (PC + πIF)- Forces In (PIF + πC )
PC = Capillary hydrostatic pressure
πIF = Osmotic force due to interstitial fluid [protein]
πC = Osmotic force due to plasma [protein]
PIF = Interstitial fluid hydrostatic pressure
33
What are the four starling forces? What do they determine?
1. PC
2. πIF
3. πC
4. PIF
1. PC = Capillary hydrostatic pressure
2. πIF = Osmotic force due to interstitial fluid [protein]
3. πC = Osmotic force due to plasma [protein]
4. PIF = Interstitial fluid hydrostatic pressure
Starling forces determine the **net filtration pressure**
34
Look at the values in the image and calculate Net Filtration Pressure at the Arterial end of the capillary
Net filtration pressure = 35 + 3 - 0 - 28 = 10 mmHg = favours **filtration**
35
Look at the image and use the values to calculate the Net filtration pressure at the venous end of the capillary
Net filtration pressure = 15 + 3 - 0 - 28 = -10mmHg = Favours absorption
36
The kidneys are ______ in location
The kidneys are _retroperitoneal_ in location
37
What is the Hilum?
Inner concave part of the kidney
38
The bladder receives innervation from the \_\_\_\_\_\_; emptying of the bladder is controlled by _______ and ________ inputs
The bladder receives innervation from the _ANS_; emptying of the bladder is controlled by _parasympathetic_ and _sympathetic_ inputs
39
What are the two major divisions of the nephron?
Where are they located?
* Renal corpuscle
* glomerulus
* bowman's capsule
* Located in the CORTEX
* renal tubule
* Proximal convoluted tubule
* Loop of Henle
* Distal convoluted tubule
* Collecting Duct
* Located in the cortex with loop of henle extending into the renal medulla
40
What is the renal corpuscle?
* Initial blood filtering component of the nephron
* Composed of the glomerulus and the bowman's capsule
41
Blood enters the renal corpuscle through the __________ and exits the renal corpuscle through the \_\_\_\_\_\_\_
Blood enters the renal corpuscles through the _Afferent Arteriole_ and exits the renal corpuscles through the _Efferent Arteriole_
42
Outer wall of the bowman's capsule is made of _______ and surrounds the \_\_\_\_\_\_\_\_
\*Insert image from page 10 of lecture 2 slides\*
Outer wall of the bowman's capsule is made of _epithelial cells_ and surrounds the _bowman's space (where filtrate enters)_
43
What are podocytes?
Cells of the bowman's capsule which come in contact with the glomerular capillaries (on invaginated region of the bowman's capsule which forms the bowman's cup)
44
The epithelial cell layer of the bowman's capsule continues on to form the \_\_\_\_\_\_
The epithelial cell layer of the bowman's capsule continues on to form the _tubules_
* portion where processing occurs to form the urine
* function differs depending on the segment of the tubule
45
What is the ultimate outcome of the development of the renal corpuscle?
Development of a hollow tube which becomes the bowman's cup and continues on as the tubule
46
What are the three stages of Renal corpuscle development?
1. When the kidneys are forming during fetal development
* nephron develops first as a blind-ended tube (no opening)
* tube is lined by a layer of epithelial cells sitting on a basement membrane
2. Growing tuft of capillaries penetrate the expanded end of tubules
* tubule invaginates
* capillaries continue to move closer to the epithelial cell layer
* **basal lamina** is trapped in between endothelial cells of capillaries and epithelial layer
* Epithelial cell layer differentiates into **parietal** (outer) and **visceral** (inner) layers
3. The outer layer does NOT fuse with the inner layer - space between them
4. Parietal layer eentually flattened to become wall of bowman's capsule and Visceral layer becomes Podocyte cell layer
47
What is the parietal layer of the Bowman's Capsule?
The outer layer of epithelial cells which forms the outer wall of the bowman's capsule
48
What is the visceral layer of the the bowman's capsule?
The layer closest to the glomerular capillaries; cells are the podocytes
49
What is the basement membrane of the glomerular capillary (of the renal corpuscle) composed of?
Gel-like mesh structure composed of collagen proteins and glycoproteins
50
where are podocytes found in relation to the basement membrane?
Podocytes are found outside the basement membrane with filtration slits through which fluid moves
* foot processes (cytoplasmic projections) wrap around the capillaries and leave slits between them
51
what is the purpose the foot processes?
increase surface area available for filtration
52
What are the 3 layers of the glomerular capillary?
1. endothelial layer
* fenestrated to allow for filtration
2. basement membrane
* gel-like mesh made of collagen proteins and glycoproteins
3. podocytes
* have filtration slits and foot processes to increase surface area available for filtration
53
What are the two types of nephron?
1. Cortical Nephron (~85%)
* Renal corpuscle of the cortical nephrons is always found in the cortex
* tubule segment, collecting duce and distal convoluted tubule and the proximal tubule are *mostly* located in the cortex
* portions may dip into the medulla
2. Juxtamedullary (15%)
* Sit closer to the medulla area
* Renal corpuscle is in cortex but closer to medulla
* Loop of henle and ascending limb are found in the renal medulla
54
What are the 3 types of renal processes?
1. Filtration
2. Reabsorption
3. Secretion
55
What is the difference between the functions of cortical nephrons and juxtamedullary nephrons?
* Cortical nephtrons perform the three basic functions (filtration, reabsorption, secretion)
* Juxtamedullary nephrons perform the three functions AND regulate the concentration of urine
56
How do juxtamedullary nephrons regulate the concentration of urine?
* create **osmotic gradients** in the interstitial space or outside the Loop of Henle (in the medulla)
* Osmotic gradients help in water volume regulation
* retain fluid when dehydrated and produce more urine when hydrated.
57
* Afferent arteriole branches off from the _______ and diverges into the \_\_\_\_\_\_\_\_\_\_
* Brings blood into the \_\_\_\_\_\_\_\_\_
* Blood travels through the ______ in the \_\_\_\_\_\_\_\_
* Afferent arteriole branches off from the _renal artery_ and diverges into the _capillaries of the glomerulus_
* Brings blood into the _glomerular capillary network_
* Blood travels through the _Bowman's capsule_ in the _glomerulus or glomerular capillaries_
58
Blood exits the glomerulus through the _______ arteriole which branches to form a set of capillaries called the \_\_\_\_\_\_\_\_\_
Blood exits the glomerulus through the _efferent_ arteriole which branches to form a set of capillaries called the _peritubular capillary network_
* Peritubular capillaries are found around the proximal convoluted tubules
* fuse together to form the renal vein
59
Capillaries that are found mostly associated with juxtamedullary nephrons in the medullary portion of the kidney = \_\_\_\_\_\_\_\_
Vasa recta
60
Both the _______ and the _______ are important for forming the osmotic gradient
Both the _loop of henle_ and the _vasa recta_ are important for forming the osmotic gradient
61
What happens during glomerular filtration?
Fluid in the blood is filtered across the capillaries of the glomerulus and into bowman's space
* blood is brought to the kidneys by the renal artery and then enters the glomeruli through the afferent arterioles, where it undergoes glomerular filtration
62
What are the three basic processes in the production of urine
1. Glomerular filtration
* fluid in blood filtered across capillaries of glomerulus into bowmans space
2. Tubular reabsorption
* movement of substance from the lumen back into the blood
3. Tubular secretion
* movement of nonfiltered substances from the capillaries into the tubular lumen
63
What is tubular reabsorption?
* Movement of a substance from inside the tubule into the blood
* eg: glucose is reabsorbed as it is a very important energy source
64
What is tubular secretion?
Movement of nonfiltered substances from the capillaries into the tubular lumen
* waste products that did not undergo filtration can be removed from the blood via tubular secretion
65
Urinary excretion: Blood is filtered at the ______ and then substances are added _________ to the tubules while other substances are \_\_\_\_\_\_
Urinary excretion: Blood is filtered at the _glomeruli_ and then substances are added _(secreted)_ to the tubules while other substances are _reabsorbed_
66
What are the filtration layers?
Layers that substances cross as they moved from the lumen of the glomerular capillareis into Bowman's space
Include:
* Capillary endothelial layer
* Basement membrane
* Podocytes with filtration slits
67
What is filtered out of the blood at the glomerulus?
Almost everything except **large proteins** (albumin), large anions and **blood cells**
* **water, electrolytes, glucose**, amino acids, fatty acids, vitamins and **waste products** such as urea, uric acid and creatinine
68
Why aren't proteins filtered at the glomerulus?
(4)
* Fenestrations in the capillary endothelium are not large enough to allow proteins to pass through
* Fenestrations (pores) have negative charges and thus repel the negative charge on some proteins
* Basement membrane also has negative charge
* Foot processes of the podocytes interdigitate and form **filtration slits**
* slits remain covered with fine semiporous membranes made up of proteins such as nephrins and podocins
69
* Foot processes of the podocytes interdigitate and form \_\_\_\_\_\_\_\_\_\_
* these are covered with ____________ made up of proteins such as _______ and \_\_\_\_\_\_\_\_
* Foot processes of the podocytes interdigitate and form _filtration slits_
* these are covered with _fine semiporous membranes_ made up of proteins such as _nephrins_ and _podocins_
70
How is the concentration of a substrate filtered through the filtration layers different in the plasma and in the filtrate?
The concentration of a substrate filtered through the filtration layers is *the same* between the plasma and the filtrate
71
What is ultrafiltrate?
the cell free fluid that has come into bowman's space and, except for plasma proteins (and substances bound to them) and blood cells, contains mostly all the substances at the same concentrations as in the plasma
72
What is proteinuria?
A condition where some of the proteins that are not supposed to pass through the filtration barrier show up in the filtrate and ultimately in the urine
73
What could a mutation in the synthesis of podocins and nephrins result in?
Recall: Podocins and nephrins make up the semiporous membranes covering the filtration slits of podocytes to assist in the prevention protein filtration at the glomerulus
* mutation in these proteins would resule in proteinuria (protein filtered at glomerulus into bowman's space and showing up in the urine)
74
What are the forces involved in Glomerular filtration?
(3)
* PGC
* Glomerular capillary hydrostatic pressure
* hydrostatic pressure of the blood that is found in the glomerulus (pushes fluid out of capillary and into bowman's space = favours filtration)
* 60mmHg
* PBS
* Bowman's space hydrostatic pressure
* fluid pressure in bowman's space
* opposes filtration
* 15mmHg
* πGC
* Osmotic force due to proteins in the plasma
* Higher [protein] in plasma than in bowman's space
* opposes filtration
* 29mmHg
75
What is PGC
PGC
* Glomerular capillary hydrostatic pressure
* hydrostatic pressure of the blood that is found in the glomerulus (pushes fluid out of capillary and into bowman's space = favours filtration)
* 60mmHg
76
What is PBC
PBS
* Bowman's space hydrostatic pressure
* fluid pressure in bowman's space
* opposes filtration
* 15mmHg
77
What is πGC
πGC
* Osmotic force due to proteins in the plasma
* Higher [protein] in plasma than in bowman's space
* opposes filtration
* 29mmHg
78
What is the Net glomerular filtration pressure?
Sum of the three forces (PGC, PBS, πGC)
Forces favouring filtration - forces opposing filtration
Net filtration = PGC - PBS - πGC
= 60 - 15 - 29 = 16mmHg
* Positive pressure = pushes protein free filtrate from the plasma out of the glomerulus into Bowman's space
79
What is the osmotic force due to proteins in the Bowman's space (πBS)
Zero in a healthy individual because there should be NO proteins in the Bowman's space
80
What factor would contribute to an increase in the glomerular filtration rate?
High blood pressure
* Increase in BP would increase glomerular filtration rate
81
What factor would result in a decrease in the glomerular filtration rate?
Increase in the protein concentration in the plasma would increase the protein content in the glomerular capillaries (increase πGC) thus decreasing glomerular filtration rate
82
What is "filtration fraction"
* Plasma volume entering the afferent arteriole = 100%
* **20%** of the plasma volume is filtered into Bowman's space, this is the filtration fraction
83
What happens to the 80% of plasma that is not filtered into Bowman's space?
Of the 20% that is filtered, how much is excreted?
* The 80% leaves through the efferent arterioles into the peritubular capillaries and eventually back into the main circulation
* Of the 20% that is filtered, 19% is reabsorbed into the peritubular capillaries
* ~1% of the volume that was filtered will be excreted to the external environment
84
The volume of fluid filtered from the glomerulus into the Bowman's space per unit time is called the:
Glomerular filtration rate
85
What is a normal Glomerular filtration rate?
What is this number used for in a clinical setting?
* 125mL/minute OR 180L/day \*Not a fixed Value\*
* Used to look at the health of the kidney
86
What are four factors that affect Glomerular Filtration Rate (GFR)?
1. Net glomerular filtration pressure (blood pressure)
2. Neural and endocrine control
3. Permeability of the corpuscular membrane
4. surface area available for filtration
87
GFR remains fairly constant despite large changes in arterial pressure or renal blood flow due to \_\_\_\_\_\_\_
* Glomerular filtration rate remains fairy constant as the _________ changes from 80mmHg to 180mmHg
GFR remains fairly constant despite large changes in arterial pressure or renal blood flow due to **_autoregulation_**
* Glomerular filtration rate remains fairy constant as the _mean arterial pressure_ changes from 80mmHg to 180mmHg
88
Autoregulation is regulated by changes in the _______ as well as by the _________ effect
Autoregulation is regulated by changes in the _myogenic reflex_ as well as by the _tubuloglomerular_ effect
89
In what range of mean arterial blood pressure can the glomerular filtration rate remain fairly constant?
80mmHg to 180mmHg
90
Resistance changes in the renal arterioles alter ______ and \_\_\_\_\_\_\_\_
Resistance changes in the renal arterioles alter _renal blood flow_ and _glomerular filtration rate_
91
How can resistance of the afferent arteriole be changed to alter how much blood is coming in?
* Constriction of the afferent arteriole
* due to **myogenic response**
* Constriction **increases** resistance to flow and will **decrease renal blood flow** to the glomerulus
* Decrease in renal blood flow reduces the hydrostatic pressure of the glomerular capillary (PGC) resulting in **decrease in the glomerular filtration rate**
92
What causes constriction of the afferent arteriole and how will this constriction alter GFR?
* Constriction due to **myogenic response**
* Increases resistance afferent in arterial = decreases renal blood flow = decrease PGC = **decrease glomerular filtration rate**
93
What are four scenarios that can alter GFR?
1. **Constrict afferent arteriole**
* Decrease PGC = decrease GFR
2. **Constrict efferent arteriole**
* volume of blood builds up in the glomerular capillaries = increase PGC = Increase GFR
3. **Dilate efferent arteriole**
* Decrease resistance = renal blood will drain rapidly = decrease PGC = decrease GFR
4. **Dilate afferent arteriole**
* increase BF to afferent arteriole = increase PGC = Increase GFR
94
How will each of the following scenarious affect GFR?
1. Constrict afferent arteriole
2. Constrict efferent arteriole
3. Dilate efferent arteriole
4. Dilate afferent arteriole
1. Constrict afferent arteriole
* Decrease PGC= decrease GFR
2. Constrict efferent arteriole
* volume of blood builds up in the glomerular capillaries = increase PGC = Increase GFR
3. Dilate efferent arteriole
* Decrease resistance = renal blood will drain rapidly = decrease PGC= decrease GFR
4. Dilate afferent arteriole
* increase BF to afferent arteriole = increase PGC= Increase GFR
95
What is the myogenic response?
Myo = muscle
Arteriole smooth muscle contracts or relaxes in response to increases or decreases in pressure
96
What is tubular glomerular feedback? (tubuloglomerular feedback)
* Juxtaglomerular apparatus has tubuloglomerular feeback
* controls the autoregulatory processes and affects the glomerular filtration rate depending on the volume flowing through the JGA
* Tubuloglomerular feedback is an adaptive mechanism that links the rate of glomerular filtration to the concentration of salt in the tubule fluid at the macula densa
97
What is the juxtaglomerular apparatus (JGA)?
* specialized structure formed by the **distal convoluted tubule** and the **glomerular afferent arteriole**
* Next to the glomerulus
* Helps control GFR via tubuloglomerular feedback
98
What are three cell types that control glomerular filtration rate at the JGA?
1. Macula densa
2. Juxtaglomerular cells
3. Mesengial cells (NOT CONSIDERED PART OF THE JGA)
99
What is the macula densa?
Cells of the juxtaglomerular apparatus:
* on wall of distal tubule at the junction where the ascending limb is beginning to form the distal tubule
* close proximity to the glomerulus
* sense increase in sodium and increased flow through distal tubule
* secrete vasoactive compounds
* By paracrine effects changes afferent arteriole resistance
* adenosine is a paracrince factor which has an effect on arteriolar resistance by signalling JG cells
100
What are juxtaglomerular cells?
Cells of the Juxtoglomerular apparatus (JGA)
* aka granular cells
* sit on top of the afferent arteriole
* innervated by sympathetic nerve fibres which can change the resistance of the afferent arteriole
* Release **renin** which controls afferent arteriole resistance
101
What are mesangial cells?
Found in the triangular region between the afferent and efferent arterioles
* Not considered part of JGA
* Contraction allows podocytes to contract
* shrinks surface area of glomerular filtration surface
* contribute to controlling filtration surface area which affects the GFR
102
Which cells of the JGA secrete vasoactive compounds and sense increased sodium and increased flow through the distal tubule?
Macula densa cells on the wall of the distal tubule
103
What cells of the JGA secrete renin?
Juxtaglomerular cells on top of the afferent arteriole
104
What is the role of the macula densa in tubuloglomerular feedback?
* When increased fluid volume flows through the distal tubule, there is a feedback effect on the glomerular structure in controlling the GFR
* Increase in the GFR = Increase flow to the tubule = flow past macula densa increases = paracrine factors from the macula densa are secreted = act on afferent arteriole = constricts = resistance in afferent arteriole increases = PGC decreases = GFR decreases
105
What is filtered load?
How is it calculated?
* The amount of a substance that is filtered by the kidneys per day or, how much of the load is filtered into bowman's space
* Calculated by multiplying the glomerular filtration rate by the concentration of the substance in the plasma
* Filtered load = (GFR)([substance in plasma])
* eg: filtered load of glucose:
* [glucose] in blood = 1g/L
* GFR = 180L/day
* Filtered load (glucose) = (180)(1) = 180g/day
106
What is indicated if the substance excreted in urine is **less** that the filtered load of that substance?
Reabsorption has occurred
107
What is indicated if the substance excreted in the urine is **more** than the filtered load?
Secretion has occurred
108
What is indicated by each of the 3 figures?
1) Filtration + secretion = 100% secretion
2) Filtration + partial reabsorption = only small amount shows in urine (less than filtration fraction)
3) Filtration + complete reabsorption = 100% reabsorption (eg glucose)
109
What are two examples of substances that undergo only filtration (ie whatever is filtered is excreted, no reabsorption, and no secretion)
1. Inulin
* freely filtered
* Filtered only and what is filtered is excreted completely in the urine
* No secretion or reabsorption
* A polysaccharide that is found in vegetables and plants
2. Creatinine
* Filtered only and what is filtered is excreted completely in the urine
* No secretion or reabsorption
110
What is ultrafiltrate?
the protein-free fluid formed as the plasma is filtered at the glomerulus; the **concentration of substances in the filtrate and in the plasma**, except for plasma proteins (and blood cells), **should be the same**
111
Approximately \_\_% of the plasma that enters into the glomerular capillaries is filtered into Bowman’s space; this is the \_\_\_\_\_\_\_\_
Approximately _20_% of the plasma that enters into the glomerular capillaries is filtered into Bowman’s space; this is the _filtration fraction_
112
Provide an example of a substance that would undergo filtration and partial reabsorption
Electrolytes (eg sodium)
113
What types of substances (2) would we expect to see to undergo filtration and complete reabsorption?
Glucose and Amino Acids
114
What types of molecules would we expect to be filtered and secreted?
Organic acids (PAH: para-aminohippuric acid) and bases
\*PAH measures renal plasma flow\*
115
What molecule is often used clinically to measure renal plasma flow?
Para-aminohippuric acid (PAH) – an organic acid that undergoes filtration and secretion
116
The reabsorption of _\_\_\_\_\_\__ is not physiologically regulated
The reabsorption of _glucose_ is not physiologically regulated
117
The body regulates the reabsorption of _\_\_\_\__and _\_\_\_\_\__
The body regulates the reabsorption of _water_ and _sodium_
118
What are the two pathways of reabsorption?
1. Diffusion across tight junction (paracellular = in between cells) - minor
2. Mediated transport (transepithelial) - major
* tubular lumen → cell → interstitial space → peritubular capillary
119
How is sodium reabsorbed?
At the Luminal/apical surface?
At the basolateral membrane?
1. Na+ diffuses passively down it's concentration gradient from the lumen, across the apical membrane into the cell
2. Na+ is then actively transported out of the cell across the basolateral membrane via the Na+/K+ pump (req ATP)
* 3 Na+ out (into interstitial space) 2 K+ in
3. Na+ then moves into the peritubular capillaries through bulk flow
120
During sodium reabsorption, Na+ is moved across the apical membrane via diffusion down its concentration gradient. What establishes that concentration gradient?
Sodium enters the cell down its gradient because of the active transport of sodium on the basolateral side by the Na+/K+ pump
* Filtrate in the lumen has a high [Na+] and inside the proximal tubule cell there is a low [Na+] which is maintained due to the actions of the Na+/K+ pump
121
The low concentration of sodium inside the cell causes sodium to move into the cell from the tubule lumen;
* there is a _\_\_\_\_\_\_\_\__ driving sodium into the cell
* This low concentration of sodium inside the cell is maintained due to the actions of the _\_\_\_\_\_\_\__in the _\_\_\_\_\_\_\_\_\__
* Once the sodium enters the cell from the lumen, it is pumped out into the interstitial fluid through the _\_\_\_\_\_\_\__
The low concentration of sodium inside the cell causes sodium to move into the cell from the tubule lumen;
* there is a _concentration gradient_ driving sodium into the cell
* This low concentration of sodium inside the cell is maintained due to the actions of the _Na+ /K + pump_ in the _basolateral membrane_
* Once the sodium enters the cell from the lumen, it is pumped out into the interstitial fluid through the _Na+ /K + pump_
122
Transepithelial transport of sodium is _\_\_\_\_\_\_\_\_\_\_\_\_\__:
* On the basolateral membrane, transport of sodium is mediated by the_**\_\_\_\_\_\_\_\_\_\_\_\_\_**_
* On the **luminal/apical membrane**, the influx of sodium occurs as sodium flows into the cell due to _\_\_\_\_\_\_\_\_\_\_\_\_\__
* This occurs as well with the use of a _\_\_\_\_\_\_\_\_\_\_\_\_\__
* Sodium accumulates in the _**\_\_\_\_\_\_\_\_\_\_\_\_\_**_and then moves into the _\_\_\_\_\_\_\_\_\_\_\_\_\__
* Sodium moves into the capillary by _\_\_\_\_\_\_\_\_\_\_\_\_\__or _\_\_\_\_\_\_\_\_\_\_\_\_\__
Transepithelial transport of sodium is _mediated transport_:
* On the basolateral membrane, transport of sodium is mediated by the _Na+ /K + pump_
* On the **luminal/apical membrane**, the influx of sodium occurs as sodium flows into the cell due to _its concentration gradient_ (high [Na+] in lumen and low [Na+] in cell)
* This occurs as well with the use of a _membrane protein_
* Sodium accumulates in the _interstitial fluid_ and then moves into the _peritubular capillaries_
* Sodium moves into the capillary by _diffusion_ or _bulk transport_
123
At normal plasma glucose concentrations, what is the clearance of glucose?
Zero = no glucose is excreted in the urine
124
All filtered glucose is reabsorbed, how is this accomplished?
* proximal tubule
In the proximal tubule, glucose is reabsorbed by:
* **Active transport** on the *luminal* side by **SGLT protein** (sodium-glucose linked transporters)
* **Facilitated diffusion** on the *basolateral* side using carrier protein **GLUT** (glucose transporter)
* Carrier-mediated facilitated diffusion
125
What is glucosuria?
When glucose appears in the urine because it is above the renal threshold (ie exceeds transport maximum Tm)
126
What is the transport maximum (Tm)
Limit of substance that can be transported/time
127
What two types of transporters are involved in the reabsorption of glucose?
1. Sodium-linked glucose transporter (**SGLT**) = sodium-dependent glucose reabsorption
* on the *apical membrane* of the cell
* uses inwardly directed [Na+] gradient (as energy) to drive the influx of glucose into the cell against its concentration gradient
* **Secondary Active transport**
2. **GLUT** (Glucose transporter) = carrier-mediated facilitated diffusion
* Glucose concentration is higher in cell than in the interstitial fluid therefore it diffuses across the *basolateral membrane* using the GLUT protein
128
Describe graph A
* Filtration rate of glucose is proportional to your plasma glucose concentration
* If your plasma [glucose] increases, the filtration rate of glucose will increase
* glucose will be filtered through the glomerulus
* Linear relationship
129
Describe Graph B:
* Initially, when plasma glucose concentration increases, reabsorption by the kidney will increase; a linear relationship
* Reabsorption of glucose is linear up to _\_\_\_\_\_\_\_\_\_\_\_\_\__
* Body's normal range of reabsorbing glucose is between _\_\_\_\_\_\_\_\_\_\_\_\_\__
* After _\_\_\_\_\_\_\_\_\_\_\_\_\__, the graph reaches plateau
* no more reabsorption after this point
* this is the _\_\_\_\_\_\_\_\_\_\_\_\_\__
* At Tm all the _\_\_\_\_\_\__ proteins that transport glucose from the *lumen* to the *peritubular* *capillaries* are _saturated_
* all the binding sites are occupied and cannot transport any more glucose - the graph plateaus
* Initially, when plasma glucose concentration increases, reabsorption by the kidney will increase; a linear relationship
* Reabsorption of glucose is linear up to _~300mg/100mL plasma_
* Body's normal range of reabsorbing glucose is between _100-200mg/100mL plasma_
* After 300mg/100mL plasma, the graph reaches plateau
* no more reabsorption after this point
* this is the **_transport maximum_**
* At Tm all the _SGLT_ proteins that transport glucose from the lumen to the peritubular capillaries are saturated
* all the binding sites are occupied and cannot transport any more glucose - the graph plateaus
130
Describe Graph C:
* Normally glucose should not be found in the urine
* When will glucose show up in the urine?
* What is the Transport maximum of glucose and what happens once it's reached?
* What is the known renal threshold (Tm) of glucose?
* Normally glucose should not be found in the urine
* Glucose will show up in the urine if the body’s limit for handling glucose has been reached
* At **300 mg/100 mL plasma** the transport maximum for glucose has been reached and there is **no additional reabsorption of glucose**
* 300 mg/100 mL is known as the renal threshold
* *Beyond this value, glucose comes out in the urine*
* This occurs in a diabetic person
131
What establishes the Transport maximum?
The transport maximum is the limit of substance that can be transported/unit time
* Binding sites of transport proteins become saturated
* All binding sites are occupied
* Filtered load exceeds the limit of reabsorption
132
What establishes the glucose transport maximum?
* **Each SGLT protein can only bind to one glucose and each cell has a finite number of SGLT proteins**
* Limit to the number of glucose molecules that can be picked up on the luminal side of the cell = Tm
* When there is too much glucose in the filtered load in the lumen, glucose shows up in the urine
133
What are two conditions that could be indicated by glucose in the urine?
1. **Diabetes mellitus**
* capacity to reabsorb glucose is normal but filtered load is greatly increased (beyond the threshold level for glucose reabsorption in the tubules)
* **SGLT** are functioning
* Too much glucose in the blood because insulin not working properly
2. **Renal glucosuria**
* *****benign glucosuria* or *familial renal glucosuria*
* Genetic mutation of the **Na+/glucose cotransporter** (SGLT)
* normally mediates active reabsorption of glucose in the proximal tubules
* These mutations of SGLT result in the inability to transport glucose from the luminal side and across the peritubular capillaries
* Filtered load may be small/normal but glucose shows up in the urine because SGLT cannot transport glucose (low reabsorption)
134
How does Diabetes mellitus cause glucose to show up in the urine?
**Diabetes mellitus**
* capacity to reabsorb glucose is normal but the filtered load is greatly increased (beyond the threshold level for glucose reabsorption in the tubules)
* SGLT are functioning
* Too much glucose in the blood because insulin not working properly
135
How does renal glucosuria cause glucose to appear in the urine?
**Renal glucosuria**
* benign glucosuria or familial renal glucosuria
* Genetic **mutation** of the **Na+/glucose cotransporter (SGLT)**
* normally mediates active reabsorption of glucose in the proximal tubules
* These mutations of SGLT result in the **inability to transport glucose** from the luminal side and across the peritubular capillaries
* Filtered load may be small/normal but glucose shows up in the urine because SGLT cannot transport glucose (low reabsorption)
136
Urea is *freely filtered* at the \_\_\_\_\_\_\_\_\_
* How does the concentration of urea in the bowman's space compare to concentration of urea in the plasma
Urea is *freely filtered* at the _glomerulus_
* How does the concentration of urea in the bowman's space compare to concentration of urea in the plasma
137
Reabsorption of urea:
1. Sodium is reabsorbed by _\_\_\_\_\_\_\_\_\__
2. _\_\_\_\_\_\_\_\_\__ drives anion reabsorption
* what is an example of an anion that may move out of the lumen down its electrochemical gradient?
3. As *sodium* and *anions* are moving out of the lumen into the *extracellular fluid*, the extracellular fluid is _\_\_\_\_\_\_\_\_\__ than the fluid remaining in the lumen
4. Water now flows out of the lumen by _\_\_\_\_\_\_\_\_\__following the reabsorption of _\_\_\_\_\_\_\_\_\__ and other _\_\_\_\_\_\_\_\_\__
5. Urea will _\_\_\_\_\_\_\_\_\__ down its concentration gradient
* Urea reabsorption is dependent upon _\_\_\_\_\_\_\_\_\__ = **4 steps**
Reabsorption of urea:
1. Sodium is reabsorbed by _active transport_
2. _Electrochemical gradient_ drives anion reabsorption
* *Chloride* is an example of an anion that may move out of the lumen, down its electrochemical gradient
3. As *sodium* and *anions* are moving out of the lumen into the *extracellular fluid*, the extracellular fluid is _more concentrated_ than the fluid remaining in the lumen
4. Water now flows out of the lumen by _osmosis_ following the reabsorption of _sodium_ and other _electrolytes_
5. Urea will _diffuse_ down its concentration gradient
* Urea reabsorption is dependent upon _water reabsorption_ = **4 steps:**
1. First, water has to move
2. The concentration of urea has increased because the same amount of urea is contained in a smaller volume, as water has diffused out of the lumen
3. Urea then moves out of the lumen side into the interstitial space
4. Urea reabsorption is dependent on water reabsorption
138
In tubular secretion, substances move from the _______ to the \_\_\_\_\_\_
* Involves mostly ____ and \_\_\_\_
* 3 other substances secreted?
* Involves what kind of mediated movement?
* Coupled to \_\_\_\_\_\_\_\_
In tubular secretion, substances move from the _peritubular plasma_ to the _tubular lumen_
* Involves mostly _H+_ and _K+_
* 3 other substances secreted
* Penicillin
* Choline
* Creatinine
* Involves **active transport**
* Coupled to the reabsorption of Na+
139
How are inulin and creatinine handled differently?
Creatinine undergoes secretion;
Inulin does not undergo secretion or reabsorption (whatever is filtered is what is secreted in the urine)
140
What is **Renal Clearance?**
Way of measuring or quantifying how well the kidneys are functioning
* looks at how well the kidneys clear or remove substances
* Looks at **excretory products**
* **Measures the volume of plasma from which a substance is completely removed from the kidney per unit time**
141
Renal clearance is the volume of \_\_\_\_\_\_\_\_\_\_\_
Renal clearance is the volume of _plasma that is measured_
* when a substance is cleared from the plasma it will be removed in the urine
* As a result, the clearance for substance S is the amount, or mass of substance S, excreted per unit of time divided by plasma concentration
Clearance of "S" = USV / Ps
Cs = Clearance of S
Us = concentration of S in the urine
V = volume of urine passed (mL/min)
Ps = concentration of substance in plasma
142
What substance is used to measure clearance?
Inulin
143
What is inulin?
* Polysaccharide not found in the body
* Readily filtered but not reabsorbed, secreted, or metabolized by the tubule
* The clearance of Inulin is equal to **GFR** (filtration rate)
* Can be used to measure GFR
144
Measuring the clearance of inulin provides a measure of what?
Glomerular filtration rate (GFR)
145
What is creatinine?
How is it handled by the kidneys?
How is its clearance used clinically?
* What is creatinine?
* product of muscle metabolism
* How is it handled by the kidneys?
* filtered, not reabsorbed
* undergoes slight secretion
* clearance will be slightly higher than GFR
* How is its clearance used clinically?
* Can be used clinically to estimate GFR
* GFR is inversely proportional to the plasma concentration of the substance
146
If the clearance of a substance X is **greater** than the glomerular filtration rate of 125 millilitres per minute, substance X is being \_\_\_\_\_\_\_\_\_
If the clearance of a substance X is **greater** than the glomerular filtration rate of 125 millilitres per minute, substance X is being _secreted_
147
If the clearance of substance X is **less** than the glomerular filtration rate of 125 millilitres per minute, substance X is being \_\_\_\_\_\_\_\_\_
If the clearance of substance X is **less** than the glomerular filtration rate of 125 millilitres per minute, substance X is being _reabsorbed_
148
How are the ions Na+, Cl- and K+ handled in the nephron?
* Na+
* Actively reabsorbed
* Cl-
* Transported passively when Na+ is pumped out of the cell (follows Na+)
* K+
* secreted into the tubules mainly by cells of the **distal** and **collecting ducts**
149
What happens in the **Proximal convoluted tubule?**
The PCT
* **Reabsorbs** majority of **water** and non-waste plasma solutes
* Major site of **solute secretion** except K+
150
What happens in the Loop of Henle?
Loop of henle creates an osmotic gradient in the interstitial space
- reabsorbs large amounts of ions and not as much water
151
What happens in Distal convoluted tubule?
* Site of major physiological control for water reabsorption
* Major homeostatic mechanisms of fine control of water and solute to produce urine
152
Reabsorption or Secretion:
* Proximal convoluted tubules
* Loop of Henle
* Distal Convoluted tubules
* Nutritionally valuable substances
Reabsorption or Secretion:
* **Proximal convoluted tubules:**
* 80% reabsorptive and secretory activities
* **Loop of Henle**
* little water, but large amounts of ions are reabsorbed
* **Distal Convoluted tubules**
* 12-15% reabsorption occurs here
* **Nutritionally valuable substances**
* completely reabsorbed
153
What are two sources of water gain and 3 avenues of water loss?
Water Gain:
1. Ingested liquid
2. Water from oxidation of food
Water loss:
1. Skin, respiratory airways, insensible (not sensed) water loss
2. Sweat
3. GI tract, urinary tract, menstrual flow
154
Large volume of water (~67%) is reabsorbed in the \_\_\_\_\_\_\_\_\_\_
Large volume of water (~67%) is reabsorbed in the _proximal tubules_
* Aquaporins are always open in the proximal tubule cells (PTC's)
155
Water reabsorption is dependent on the reabsorption of \_\_\_\_\_\_\_
Water reabsorption is dependent on the reabsorption of _Na+_
* Osmotic gradient set up by Na+ reabsorption acts as the driving force for water reabsorption
156
Which region(s) of the kidney involved in water reabsorption is under physiological control?
Cortical and medullary collecting duct
157
Which hormone regulates water reabsorption?
Vasopressin or antidiuretic hormone (ADH)
158
How does ADH (aka vasopressin) regulate water reabsorption?
Regulates a specific type of aquaporin in the collecting ducts
159
In the Proximal tubule:
* Percent of filtered water reabsorbed
* Mechanism of water reabsorption
* Hormones that regulate water permeability
In the Proximal tubule:
* Percent of filtered water reabsorbed
* 67
* Mechanism of water reabsorption
* Passive (AQP-1)
* Hormones that regulate water permeability
* none
160
In the Loop of Henle:
* % of filtered water reabsorbed
* Mechanism of water reabsorption
* Hormones that regulate water Permeability
In the Loop of Henle:
* % of filtered water reabsorbed
* 15
* Mechanism of water reabsorption
* Descending thin limb, passive (AQP-1)
* Hormones that regulate water Permeability
* None
161
In the Distal tubule:
* % filtered water reabsorbed
* Mechanism of water reabsorption
* Hormones that regulate water permeability
In the Distal tubule:
* % filtered water reabsorbed
* 0
* Mechanism of water reabsorption
* No water reabsorption
* Hormones that regulate water permeability
* none
162
In the Large Distal tubule and collecting Duct:
* % filtered water reabsorbed
* Mechanism of water reabsorption
* Hormones that regulate water permeability
In the Large Distal tubule and collecting Duct:
* % filtered water reabsorbed
* 8-17
* Mechanism of water reabsorption
* Passive (AQP-2,3,4)
* Hormones that regulate water permeability
* Vasopressin/ADH
163
In the Proximal convoluted tubule, how is water transported?
* Open aquaporins allow water to move through, but _\_\_\_\_\_\_\_\_\_\__ has to take place
1. **Na+ /K+ pump** on the _\_\_\_\_\_\_\_\_\_\__side of the tubule cell drives _\_\_\_\_\_\_\_\_\_\__ out of the cell into the _\_\_\_\_\_\_\_\_\_\__ fluid
2. This creates a _\_\_\_\_\_\_\_\_\_\__concentration of sodium *inside* the tubular cell, providing a gradient for the movement of _\_\_\_\_\_\_\_\_\_\__ from the _\_\_\_\_\_\_\_\_\_\__
3. Sodium transport into the cell _\_\_\_\_\_\_\_\_\_\__ local osmolarity in the tubular fluid adjacent to the cell
1. Therefore the water concentration has _\_\_\_\_\_\_\_\__ compared to the interstitial fluid
2. Water will move through the cell from the _\_\_\_\_\_\_\_\_\__into the _\_\_\_\_\_\_\_\_\_\__ by osmosis
3. It will move through the cell through _\_\_\_\_\_\_\_\_\_\__or through the _\_\_\_\_\_\_\_\_\_\__
In the Proximal convoluted tubule, how is water transported?
* Open aquaporins allow water to move through, but _sodium reabsorption_ has to take place
1. **Na+ /K+ pump** on the _basolateral_ side of the tubule cell drives _sodium_ out of the cell into the _interstitial_ fluid
2. This creates a _lower_ concentration of sodium *inside* the tubular cell, providing a gradient for the movement of _sodium into the cell_ from the _tubular_ _lumen_
3. Sodium transport into the cell _decreases_ local osmolarity in the tubular fluid adjacent to the cell
1. Therefore the water concentration has _gone up_ compared to the interstitial fluid
2. Water will move through the cell from the _luminal side_ into the _interstitial side_ by osmosis
3. It will move through the cell through _aquaporin I_ or through the _tight junctions_
164
Explain how water is reabsorbed through the thin descending portion of the loop of henle:
Through aquaporins (diffusion/osmosis)
165
How is water reabsorbed in the ascending limb of the loop of henle?
Ascending limb of loop of henle is impermeable to water = no water leaves
* Salt is reabsorbed through thick ascending portion of loop of henle
166
What characteristics of the Loop of Henle allow for countercurrent multiplication? What is the outcome of countercurrent multiplication?
* The loop of henle is a single tubule with two sides very closely juxtaposed
* Fluid streams in opposite direction
* Each side has different transport capabilities
* **Descending limb**: water can diffuse out from the tubule lumen into the interstitial space
* **Ascending** **limb**: impermeable to water
* Creates an osmotic gradient
167
What is the Net result of the actions of the descending and ascending limbs of the loop of henle?
* Loop of henle
* Descending limb (300mOsm/L - normal plasma osmolarity)
* Ascending limb - active transport of NaCl
* impermeable to water
* Interstitial fluid is hyperosmotic compared to ascending limb fluid
* Net Result:
* Gradient difference between the interstitial space/descending limb and ascending limb of **200mOsm** (ALWAYS a difference of 200mOsm)
168
What is the goal of the descending limb of the loop of henle?
To create a hyperosmolar interstitial environment in the interstitial fluid
169
Multiplication of the gradient down the length of the loop of henle is called the \_\_\_\_\_\_\_\_\_
Multiplication of the gradient down the length of the loop of henle is called the _countercurrent multiplier_
170
Fluid becomes concentrated in the \_\_\_\_\_\_\_\_\_
- Dilutes fluid again as it goes through the _______ and enters the distal tubule
* Distal tubule has very dilute fluid (100mOsm/L)
* _\_\_\_\_\__works on the collecting duct and fluid inside the tubule becomes _\_\_\_\_\_\__ with the interstitial space (300Osm/L)
* More water is reabsorbed from the cortical collecting duct due to _\_\_\__ effect
* High osmolarity gradient that is established in the interstitial space helps the water to _\_\_\_\_\_\_\_\_\_\_\_\_\__
Fluid becomes concentrated in the _descending limb_
- Dilutes fluid again as it goes through the _ascending limb_ and enters the distal tubule
* Distal tubule has very dilute fluid (100mOsm/L)
* _ADH_ works on the collecting duct and fluid inside the tubule becomes _isoosmotic_ with the interstitial space (300Osm/L)
* More water is reabsorbed from the cortical collecting duct due to _ADH_ effect
* High osmolarity gradient that is established in the interstitial space helps the water to _permeate out of the medullary collecting tubule_
171
What is the vasa recta?
Blood vessels that run parallel to the Loop of Henle
* counter current bloodflow (blood flows through in one direction and out the other)
172
Why is a hyperosmotic interstitial gradient created?
To absorb water into the interstitial space
- created by juxtamedullary nephrons (deep in medulla, surrounded by vasa recta)
173
What type of nephrons create the hyperosmotic interstitial gradient?
Juxtamedullary nephrons
174
What are three ways that the vasa recta helps with countercurrent exchange?
1. Blood flow in the vasa recta serves as countercurrent exchangers
* helps in maintaining the Na+ and Cl- gradient
* *Gradient is not washed away*
2. Blood flow in medulla is low
* less than 5% of the total renal blood flow and is sluggish
* prevents solute loss
3. The capillaries are freely permeable to ions, urea and water and they move in and out of the capillaries in response to the concentration gradients
* Vasa recta does not create medullary hyperosmolarity, but prevents it from being washed out, therefore, it maintains it
175
Compare filtrate flow through the loop of henle to blood flow through the vasa recta
Blood flow in the vasa recta is in the opposite direction to fluid flow in the Loop of Henle
176
what is the purpose of the Vasa Recta?
* Permeable to \_\_\_\_\_\_\_\_\_\_\_
* Therefore;
what is the purpose of the Vasa Recta?
* Permeable to both _salt, urea and water_
* Therefore:
* Reinforces the gradient created by the renal rubules by exchange of salt and water
* Leads to increase in Na+ and urea concentration in the renal medulla intersitial space
177
What mechanism of the Vasa Recta is responsible for **reinforcing the gradient created by the renal tubules leading to increased [Na+] and [urea] in the renal medulla interstitial space?**
* The vasa recta is permeable to solutes (salt, urea) and water
* NaCl moves out of the ascending limb (active transport) of loop of henle to enter the descending limb of vasa recta as blood enters the descending limb of the vasa recta
* water diffuses out of the descending limb into the ascending limb
Leads to increase in Na+ and urea concentration in the renal medulla interstitial space
178
What is the function of the vasa recta?
How does blood entering the vasa recta compare to blood exiting the vasa recta?
The loop-like vasa recta maintain the gradient established by the loop of Henle. The blood is only slightly higher in osmolarity when it leaves the vasa recta compared to when it entered the vasa recta
179
What is the fate of filtered Urea?
\*\*\* how much of the filtered urea is excreted?
(Recycling and Trapping of Urea)
* Urea is a waste product
* 50% of the filtered urea is reabsorbed in the proximal tubule
* trapped in the interstitial space to maintain gradient
* 50% secreted BACK into the Loop of Henle
* 100% of the urea enters the Distal Convoluted Tubule
* 30% reabsorbed again from cortical collecting duct
* 55% reabsorbed from the IMCD (inner medullary collecting duct)
* helped by ADH
* 5% diffuses out of the vasa recta
* 50% recycled (secreted) back into the tubule
* Minimal uptake of urea by vasa recta and recycling urea in the interstitial space helps in maintaining high osmolarity in the medulla
* **15% of original amount is excreted** (Much less than filtered amount)
180
How much of the original amount of filtered urea is secreted?
15%
181
How is urea used in maintaining the high osmolarity in the medulla?
Minimal uptake of urea by vasa recta and recycling urea in the interstitial space helps maintain high osmolarity in the medulla
182
What 5 mechanisms help to maintain the hyperosmotic environment of the medulla?
1. Counter-current anatomy and opposing fluid flow through the Loop of Henle of the Juxtamedullary nephrons
2. Reabsorption of NaCl in the ascending limb
3. Impermeability of ascending limb to water
4. Trapping of urea in the medulla
5. Hairpin loops of vasa recta maintains the hyperosmotic interstitium in the medulla
183
Why is there a need for concentrated urine?
Kidneys save water by producing hyperosmotic urine
184
\_\_\_\_\_\_ regulates water reabsorption in the collecting ducts
_ADH_ regulates water reabsorption in the collecting ducts
185
Because the sodium concentration and the extracellular body fluid volume are closely linked, any changes in total [Na+] would lead to changes in _______ and \_\_\_\_\_\_\_
Because the sodium concentration and the extracellular body fluid volume are closely linked, any changes in total [Na+] would lead to changes in _blood volume_ and _blood pressure_
186
How is plasma osmolarity determined?
By measuring plasma sodium concentration
187
What dictates how much water will be excreted?
What exerts physiological control of water reabsorption/excretion?
1. Volume of water reabsorption dictates how much water will be excreted
2. Physiological control of water reabsorption/excretion is exerted by ADH (antidiuretic hormone) also called vasopressin
188
What is diuresis?
Void/produce a large amount of urine
189
What is antidiuresis?
Reduction in or suppression of the excretion of a large volume of urine
190
What type of hormone is ADH (vasopressin/antidiuretic hormone) and where is it made?
Peptide hormone made in the hypothalamus
(released by pituitary gland)
191
What stimulates the release of ADH?
Cells in the hypothalamus sense the osmolarity of the plasma
* reduction in plasma volume
192
\_\_\_\_\_\_\_\_\_\_\_ cells in the hypothalamus that make ADH are found in the \_\_\_\_\_\_\_\_\_\_\_
_Neurosecretory_ cells in the hypothalamus that make ADH are found in the _Supraoptic nucleus (SON)_
called "sensors of osmolarity"
193
What cells are known as the "sensors of osmolarity"?
Neurosecretory cells in the hypothalamus found in the supraoptic nucleus
194
What is the site of action of ADH?
Collecting ducts
195
What type of aquaporin is found in the proximal convoluted tubules?
AQP1
196
What type(s) of aquaporins are found in the collecting ducts?
AQP2,3,4
197
AQP2 insertion on the _____ side is regulated by ______ *via \_\_\_\_\_\_\_\_\_\_*
AQP2 insertion on the _laminal_ side is regulated by _ADH_ *via* _AQP2 gene transcription_
198
Are AQPs on the basolateral membranes of the CD regulated by ADH?
No, AQPs 3 and 4 on the basolateral side are not regulated.
ADH causes the insertion of AQP2 into the laminal side via gene transcription
199
How does ADH regulate aquaporin 2 in the collecting ducts?
1. ADH or vasopressin binds to the receptor on the cell
2. Activates adenylyl or adenylate cyclase
3. ATP is converted to cAMP
4. Activates protein kinase A PKa
5. Phosphorylates proteins
6. Transcription factors are activated
7. AQP2 protein is up-regulated
8. AQP2 proteins are inserted into the luminal membrane
9. Water can move in from the tubular lumen into the cell
10. Water then diffuses out of the cell into the interstitial fluid via AQP3 and AQP4
200
In the absence of ADH, the _______ are almost impermeable to water.
In the absence of ADH, the _collecting ducts_ are almost impermeable to water (not enough AQP2).
= would pee a lot
201
Absence of ADH leads to \_\_\_\_
Absence of ADH leads to _diuresis_
202
What is diabetes insipidus?
Pathological status of diuresis:
* Associated with large quantities of urine
203
What are the two different causes of diabetes insipidus?
1. Nephrogenic Diabetes Insipidus:
* ADH is secreted in a normal matter from the pituitary but the hormone doesn't function normally
* problem with the receptor or intracellular signaling pathway
* problem within the cells of the nephron
2. Central diabetes insipidus
* Failure to release ADH from the posterior pituitary
204
↑ADH → ___ AQP2 → ____ of water
↓ADH → ___ AQP2 → ____ of water
↑ADH → _↑_ AQP2 → _reabsorption_ of water
↓ADH → ↓ AQP2 → _excretion_ of water
205
What do osmoreceptors and thirst receptors sense?
Changes in osmolarity and volume
206
What happens to osmolarity of plasma during water deprivation?
Water deprivation → ↑osmolarity of plasma → osmoreceptors in the hypothalamus are stimulated → ↑ADH release → retention of water
= **antidiuresis** - reduction in urine volume
- also stimulates thirst centres in hypothalamus
207
How does water intake change ADH secretion?
Water intake → lower the osmolarity of plasma → osmoreceptors in the hypothalamus sense a block → ADH release is blocked → large volume of fluid is excreted
* Large water diuresis
208
When is sodium secreted into the renal tubules?
Sodium is never secreted into the renal tubules
it is excreted:
* Sodium excreted = Sodium filtered - sodium reabsorbed
209
How are Na+ levels physiologically regulated?
By changing the volume of urine excreted
210
How is Na+ regulated:
When we have low [Na+] in plasma?
(short term vs long term)
* Short term handling of low levels (Baroreceptors regulate GFR)
* Long-term:
* Aldosterone facilitate Na+ reabsorption
* Renin, angiotensin II needed for aldosterone secretion
211
What happens if we have high [Na+] in the plasma?
ANP (atrial natriuretic peptide) regulates GFP and inhibits Na+ reabsorption
ANP also woks by inhibiting aldosterone actions
212
Baroreceptors responds to ____ changes and are used for ________ regulation of low plasma volume (low plasma volume is a reflection of low ____ levels)
Baroreceptors responds to _pressure_ changes and are used for _short-term_ regulation of low plasma volume (low plasma volume is a reflection of low _Na+_ levels)
* Nerve endings sensitive to stretch (increase/decrease BP)
213
Where are baroreceptors located?
* Carotid sinus
* Aortic arch
* major veins
* intrarenal (JG cells of JGA)
214
How do baroreceptors work?
* sense changes in blood volume, peripheral resistance
* increase/*decrease* in blood pressure causes
* Increase/*decrease* in stretch
* increase/*decrease* in nerve impulse frequency
* Baroreceptor info is processed in the medulla oblongata
* Activation of the ANS
Role of baroreceptors image
215
Aldosterone is a _____ hormone released from the \_\_\_\_\_\_\_\_
Aldosterone is a _steroid_ hormone released from the _ad__renal cortex_
216
What triggers the release of Aldosterone?
What effect does it have?
Low plasma volume associated with low sodium.
Long-term regulation of Na+ reabsorption
217
What is the site of action of aldosterone?
Late distal tubule and cortical collecting duct
218
What is the action of aldosterone?
1. Induces synthesis of Na+ transport proteins
2. Stimulates Na+ reabsorption
3. Reduces Na+ excretion
219
Na+ reabsorption is linked to ___ secretion
Na+ reabsorption is linked to _K+_ secretion
220
What would aldosterone secretion look like in a person with a low sodium diet? high sodium diet?
High Na+ intake = low aldosterone secretion
Low Na+ intake = high aldosterone secretion
221
\_\_\_\_\_\_\_\_\_ acts on the adrenal cortex to control the secretion of aldosterone
_Angiotensin II_ acts on the adrenal cortex to control the secretion of aldosterone
222
Where is renin secreted from and what is its function?
Renin is secreted from the juxtaglomerular cells of the JGA in the kidney and is an enzyme that converts Angiotensin into Angiotensin I
223
What converts Angiotensin to Angiotensin I?
Renin
224
What converts Angiotensin I to Angiotensin II?
ACE (Angiotensin converting enzyme)
225
How does aldosterone regulate Na+ levels?
See image
226
What is the most important trigger for the release of aldosterone?
The renin-angiotensin mechanism
initiated in response to:
1. sympathetic stimulation of renal nerves
2. Decrease in filtrate osmolarity
3. Decreased blood pressure
227
What three things initiate the renin-angiotensin mechanism which triggers release of aldosterone?
1. sympathetic stimulation of renal nerves
2. Decrease in filtrate osmolarity
3. Decreased blood pressure
228
How is stretch linked to renin release?
Increased stretch (sensed by renal juxtaglomerular cells) = inhibits renin release
Decreased stretch stimulates renin release (low circulating volume)
229
Where are Juxtaglomerular cells located?
Wall of the afferent arteriole
230
Juxtaglomerular cells are __________ that sense circulating ________ and secrete \_\_\_\_\_\_\_
Juxtaglomerular cells are _mechanoreceptors_ that sense circulating _plasma volume_ and secrete _renin_
231
Juxtaglomerular cells receive three inputs:
1. Sympathetic input from external baroreceptors
2. Intrarenal baroreceptors
3. Signals from macula densa
232
What is the macula densa?
* Cells on the wall of the distal convoluted tubule
* Chemoreceptors that sense NaCl load of the filtrate
233
Where is ANP (atrial natriuretic peptide) made?
ANP is synthesized and secreted by cardiac atria
234
Site of ANP action?
On cells of several tubular segments
* ANP inhibits aldosterone
* Inhibit Na+ reabsorption
* Increases GFR and Na+ excretion
235
What stimulates ANP secretion?
Atrial natriuretic peptide is triggered by:
1. ATRIAL DISTENSION (major)
2. increased Na+ concentration
3. Increased Blood volume
236
What are three effects of ANP?
1. ANP inhibits aldosterone
2. inhibit Na+ reabsorption
3. Increases GFR and Na+ excretion
237
Most of the filtered K+ is *reabsorbed* in the _________ and \_\_\_\_\_\_\_\_
Most of the filtered K+ is *reabsorbed* in the _proximal tubule_ and _loop of Henle_
238
\_\_\_\_\_\_\_\_\_ can secrete a small amount of K+
_Collecting duct_ can secrete a small amount of K+
239
Where is the concentration of potassium (K+) in the urine regulated?
[K+] in urine is regulated in the cortical collecting duct
240
What is hyperkalemia?
Excess K+ in blood
241
What controls homeostasis of K+ in the body?
Aldosterone secreting cells in the adrenal cortex are sensitive to extracellular [K+]
* Aldosterone stimulates both Na+ reabsorption AND K+ secretion in the cortical duct
242
What happens if there is an increase in extracellular [K+]?
See image
243
How is pH related to the concentration of protons
pH = -log[H+]
High [H+] = low pH
Low [H+] = high pH
244
What is the pH for extracellular fluid?
pH for ECF is maintained between 7.35 and 7.45
245
Arterial plasma pH \< 7.35 = \_\_\_\_\_\_\_
Arterial plasma pH\>7.45 = \_\_\_\_\_\_\_
Arterial plasma pH \< 7.35 = _acidosis_
Arterial plasma pH\>7.45 = _alkalosis_
246
The sensor for low sodium chloride concentration in the blood is \_\_\_\_\_
The sensor for low sodium chloride concentration in the blood is _renin_
247
How does changing pH alter protein activity?
What effects does this have?
* Protein fxn is directly related to protein shape
* altering pH can cause a change in shape thus altering the activity
1. Changes in neuronal activity
2. Coupled to K+ imbalances
3. Irregular cardiac beats
248
What pH range is fatal in humans?
pH \< 6.8 and \>7.8 is fatal
249
What is an acid/base (Arrhenius)
Acid: releases H+ in water
Base: Accepts H+ in water
250
What does it mean that CO2 is a volatile acid?
What happens to CO2 when mixed with water?
Gas at room temperature (ie can be converted to a gaseous form and eliminated by the lungs)
CO2 + H2O → H2CO3 (carbonic acid)
251
What are two examples of nonvolatile acids important in this course?
1. Phosphoric acid
2. Sulfuric acid - produced from metabolism of sulfur-containing AA (cys, met)
252
Hydrochloric acid is produced from the metabolism of what three amino acid side chains?
1. lysine
2. arginine
3. histidine
253
Normally, will the combination of CO2 and water generate acids?
No. With certain resp diseases, CO2 can accumulate and form H2CO3 which generates H+
254
Non-volatile acids are generated from ________ and can generate \_\_\_
Non-volatile acids are generated from _protein metabolism_ and can generate _H+_
255
What are four ways in which we can gain hydrogen ions?
1. Generation of H+ from CO2 (in resp diseases CO2 accumulates → H2CO3 → H+)
2. Non-volatile acids (from metabolism of proteins) generate H+
3. Gain of H+ from the loss of bicarbonate in diarrhea
4. Gain of H+ from the loss of bicarbonate in the urine
256
What are three ways in which we can lose H+ ions?
1. Loss of H+ when vomiting
2. Loss of H+ in urines
3. Loss of H+ from hyperventilation
257
What is a buffer?
Compounds that can bind to H+ and form a hydrogen-buffer conjugate
* Buffer + H+ → HBuffer
* Reversible rxn
* Composed of a weak acid and its conjugate base
* modify or adjust the change in pH following the add'n of acids or bases
258
What are two physiological buffer systems?
(Extracellular vs intracellular)
* Extracellular buffer system is **bicarbonate** (CO2/HCO3-)
* Intracellular buffers include
* Phosphate ions and associated proteins
* Hemoglobin is an intracellular buffer
259
How is CO2 converted to bicarbonate?
1. CO2 mixes with H2O in the lungs
2. Converted to Carbonic acid via Carbonic anhydrase
3. Carbonic acid is converted to a proton and bicarbonate
4. Bicarbonate is excreted to balance H+ concentration
260
When respiration rate is not high enough, what happens as blood passes through the peripheral tissues?
Generates H+
261
\_\_\_\_\_\_ and _____ are both responsible for balancing H+ concentration within a narrow range
_Lungs_ and _kidneys_ are both responsible for balancing H+ concentration within a narrow range
262
The respiratory system (Lungs) is responsible for _____ changes in H+
The respiratory system (Lungs) is responsible for _short-term (quick)_ changes in H+
263
What causes respiratory imbalances?
1. Hyperventilation
2. Hypoventilation
3. Respiratory malfunction
264
If H+ imbalance is due to non-respiratory causes what happens to ventilation?
If imbalance is due to non-respiratory causes, then **ventilation is changed by reflex to adjust the imbalance**
* ↑ [H+] stimulates ventilation
* ↓ [H+] inhibits ventilation
265
The kidneys are responsible for _______ balance of H+ concentration
Long-term
The kidneys are responsible for _long-term_ balance of H+ concentration
266
When one H+ ions is lost from the body, what happens to bicarbonate?
When one H+ is lost from the body, 1 HCO3- is gained by the body
267
What is the kidney's response to alkalosis?
Alkalosis = decrease of plasma [H+]
* kidneys excrete more bicarbonate
* restores acid-base balance
268
What is the kidney's response to Acidosis?
Acidosis = increase in plasma [H+]
Kidney cells synthesize new bicarbonate and send it to the blood
Restores acid-base balance
269
Reabsorption of HCO3- is an ____ process dependent on \_\_\_\_\_
Reabsorption of HCO3- is an _active_ process dependent on _H+ secretion_
270
Under normal conditions, is bicarbonate (HCO3-) reabsorbed or excreted?
Normally, most of the HCO3- is reabsorbed
* occurs in the proximal tubule, ascending loop of Henle, and cortical collecting duct
271
Where does HCO3- reabsorption occur?
1. Proximal tubule
2. ascending loop of Henle
3. Cortical collecting duct
272
What happens when more H+ is secreted than there is HCO3- in the lumen to bind to the H+?
1. Extra H+ binds to HPO42- (intracellular buffer)
2. HCO3- is still generated by tubular cells and diffuses into plasma
3. NET gain of HCO3- in plasma
273
2nd Mechanism for adding HCO3- to the plasma:
1. Cells from proximal tubule are only involved
2. uptake of glutamine from glomerular filtrate or peritubular plasma
3. NH4+ and HCO3- are formed inside the cells
4. NH4+ is **actively** secreted via the Na+?NH4+ counter transport into the lumen
5. HCO3- is added to plasma
274
What is the initial buffer for acidosis? What are two other buffers?
Acidosis: initial buffer = bicarbonate
Then phosphate and then glutamine metabolism
275
What are two reasons that acidosis and alkalosis can happen?
1. Respiratory (Hypoventilation or hyperventilation)
2. Metabolic
276
How does respiratory acidosis occur?
How does the kidney respond?
* Result of decreased ventilation
* Increased blood PCO2
* Occurs in emphysema
* Kidney compensates by secreting H+ and lowers plasma [H+]
277
How does respiratory alkalosis occur?
How does the kidney respond?
* Result of hyperventilation
* Decreased blood PCO2
* Happens in high altitude
* Kidney compensates by excreting HCO3-
278
How does metabolic acidosis occur?
* Occurs in diarrhea (loss of bicarbonate ions)
* Severe exercise
* Diabetes mellitus
* Results in increased ventilation
* results in increased H+ secretion
279
How does metabolic alkalosis occur?
* Occurs after prolonged vomiting
* Results in decreased ventilation
* Increased HCO3- excretion
