Renal physiology Flashcards
(169 cards)
1
Q
What is GFR
A
Glomerular filtration rate - Rate at which plasma is filtered into filtrate by the glomerulus
2
Q
What is the gold standard for assessing GFR?
A
Inulin - Freely filtered, isn’t reabsorbed and isn’t secreted into the renal tubule
3
Q
What are the disadvantages of inulin?
A
It isn’t easy to measure and is not endogenous so needs to be infused continually at a constant rate
4
Q
What is used to measure GFR in practise?
A
Creatinine - Endogenous (Muscle metabolism), freely filtered and isn’t reabsorbed - Some is secreted, however, into the tubule so isn’t perfect
5
Q
How is eGFR calculated?
A
It is calculated using serum creatinine and a series of formulae involving age, sex and ethnicity
6
Q
What is proteinuria?
A
Presence of plasma proteins in the urine
7
Q
How is proteinuria measured?
A
24-hour urine collection or spot sample of Protein:Creatinine ratio (PCR)
8
Q
What are the 2 categories of proteinuria pathology?
A
Overflow proteinuria
Glomerular proteinuria
9
Q
What is overflow proteinuria?
A
Proteinuria caused by an excess of protein in the blood
10
Q
What is glomerular proteinuria?
A
Proteinuria caused by excessive increase in protein being absorbed by the glomerulus
11
Q
What is a cause of overflow proteinuria?
A
Myeloma - Excess of Bence-Jones protein causes proteinuria
12
Q
What can occur as a result of glomerular proteinuria?
A
Nephrotic syndrome - Albumin is lost from the glomerulus, increasing water movement into the tubules and into the ECF, causing massive oedema
13
Q
What is microalbuminuria?
A
The excretion of albumin in abnormal quantities, but still below the limit of protein detection by dipstick
14
Q
What are the 3 stages of proteinuria?
A
Microalbuminuria - -ve dipstick
Clinical proteinuria - Dipstick reading 1-2
Nephrotic syndrome - Dipstick reading ≥3
15
Q
What is PCR in renal physiology?
A
Protein:Creatinine ratio
16
Q
What is ACR?
A
Albumin:Creatinine ratio
17
Q
How much blood is filtered per day?
A
~180L
18
Q
What is osmolarity?
A
The concentration of osmotically active particles present in a solution
19
Q
What are the units for osmolarity?
A
osmol/L
mosmol/L
20
Q
What are the 2 factors that must be known to calculate osmolarity?
A
Molar concentration of the solution
Number of osmotically active particles present
(Multiply to get osmolarity)
21
Q
Osmolarity of 150mM NaCl?
A
Molar concentration = 150mM = 150 mmol/L
No. osmotically active particles =2 (Na+ and Cl-)
Osmolarity = 2 x 150 = 300 mosmol/L
22
Q
Osmolarity of 100mM MgCl2?
A
Molar concentration = 100mM = 100 mmol/L
No. osmotically active particles = 3 (Mg and 2Cl-)
Osmolarity = 3 x 100 = 300 mosmol/L
23
Q
What is the difference between osmolarity and osmolality?
A
Units
Omsolarity - osmol/L
Osmolality - osmol/Kg of water
For weak salt solutions (Including body fluids), these 2 terms are interchangeable
24
Q
What is the osmolarity of body fluids?
A
~300 mosmol/L
25
What is tonicity?
The effect a solution has on cell volume
26
What is a hypotonic solution?
One which has a lower osmolarity than the cell and so water enters the cell causing it to swell
(Takes into consideration the ability of a solute to cross the cell membrane)
27
What is an isotonic solution?
One which has the same osmolarity as the cell and so there is no change in cell volume
(Takes into consideration the ability of a solute to cross the cell membrane)
28
What is a hypertonic solution?
One with a higher osmolarity than the cell, so water leaves the cell causing it to shrink
(Takes into consideration the ability of a solute to cross the cell membrane)
29
What percentage of male body weight is total body water (TBW)?
~60%
30
What percentage of female body weight is total body water (TBW)?
~50%
31
Why is female TBW a lower percentage of body weight than male TBW?
Females have a greater percentage of body fat due to hormone differences, which contains very little water
32
What are the 2 major compartments of total body water?
Intracellular fluid (~66%)
Extracellular fluid (~33%)
33
What are some of the components of extracellular fluid?
Interstitial fluid (~80%)
Plasma (~20%)
Lymph (<1%)
Trans-cellular fluid (<1%)
34
How are body fluid compartments measured?
Using tracers to measure volume of distribution
35
What tracer is used to measure TBW?
3H2O (Tritiated water)
36
What tracer is used to measure extracellular fluid?
Inulin
37
What tracer is used to measure plasma?
Labelled albumin
38
How can ICF be measured using tracers?
Inulin to measure ECF
3H2O to measure TBW
TBW - ECF = ICF
39
How is volume of distribution measured?
- Imagine adding a dose of a tracer to a container of unknown volume of water
- Mix the tracers and allow it to equilibrate
- Then take a small sample volume and measure the concentration
- The volume of water in the container can then be calculated
- Volume = Dose ÷ Concentration
40
How does water imbalance in the body manifest?
Changes in body fluid osmolarity
Less water -> Greater osmolarity
More water -> Lower osmolarity
41
What are the main water inputs to the body?
Fluid intake
Food intake
Metabolism (Respiration by-product)
42
What are the 2 types of water output of the body?
Insensible - Losses without physiological regulation
Sensible - Losses with physiological regulation
43
What are some insensible water outputs?
Loss via skin
Loss via lungs
44
What are some sensible water outputs?
Loss via sweat
Loss via faeces
Loss via urine
45
What are some ions that are in higher concentration in the ECF?
Na+
Cl -
HCO3-
46
What are some ions that are higher in concentration in the ICF?
K+
Mg2+
Negatively charged proteins
47
What is fluid shift?
The movement of water between the ICF and ECF in response to an osmotic gradient
48
What would happen if osmotic concentration of the ECF increases (E.g. dehydration - Less water, so higher concentration of ions)
ECF becomes hypertonic to ICF
Water moves from the ICF into the ECF causing cell shrinkage and increase in ECF volume
49
What would happen if osmotic concentration of the ECF decreases (E.g. Overhydration - More water, so lower concentration of ions)
ECF becomes hypotonic to ICF
Water moves from ECF into ICF causing cell swelling and decrease in ECF volume
50
What are the 3 main challenges to fluid homeostasis?
1. Gain or loss of water
2. Gain or loss of NaCl
3. Gain or loss of isotonic fluid
51
What is caused by gain or loss of water?
Changes in fluid osmolarity
52
What is caused by ECF NaCl gain?
ECF becomes hypertonic to ICF so water moves from ICF to ECF causing ECF water gain and cell shrinkage
53
What is caused by ECF NaCl loss?
ECF becomes hypotonic to ICF so water moves from ECF to ICF causing ECF water loss and cell swelling
54
What is caused by gain or loss of isotonic fluid?
No change in osmolarity, but increased plasma volume and therefore arterial blood pressure
55
What is an electrolyte?
A substance that dissociates into free ions when dissolved
56
Why is electrolyte balance important in the body?
- Total electrolyte concentrations can affect water balance
- Concentrations of individual electrolytes can affect cell function
57
What are the 2 most important ions for electrolyte balance and why?
Na+ and K+ are particularly important as they are major contributors to the osmotic concentration and directly affect functioning of all cells
58
What is the RDA of salt?
6g (Average is around 10.5g)
59
What is the main ion found in the ECF?
Na+
60
What is the main ion found in the ICF?
K+
61
What are some problems that may be caused in changes to K+ concentration?
- Muscle weakness → Paralysis
- Cardiac irregularities → Cardiac arrest
62
Role of kidneys in maintaining plasma volume and osmolarity?
- Water balance - Excretion of water via urine
- Salt balance - Excrete around 10g salt per day
63
Role of kidneys in acid-base balance?
Excretion of H+ and reabsorption of H2CO3-
64
Role of kidneys in waste management
- Excretion of metabolic waste products (E.g. bilirubin)
- Excretion of exogenous foreign compounds (E.g. drug metabolites)
65
Role of kidneys in blood pressure maintenance?
Secretion of renin - RAAS
66
Role of kidneys in blood production
Secretion of erythropoietin (EPO) for RBC production
67
Role of kidneys in vitamin D
Conversion of vitamin D into active form (Calcitriol - Controls Ca2+ absorption in the GI tract)
68
What is the functional unit of the kidney?
Nephron (~ 1 million in the kidney)
69
What are the 3 functional mechanisms of urine production by the nephron?
1. Filtration
2. Reabsorption
3. Secretion
70
Describe the basic flow of urine in the nephron
Blood travels through the afferent arteriole into the glomerulus
Here the plasma is filtered into the Bowman's capsule
It travels through the proximal convoluted tubule
Then the descending limb of the loop of Henle
Then the ascending limb of the loop of Henle
Then the distal convoluted tubule
Then into the collecting duct
71
Describe the basic flow of urine after the nephron
Collecting ducts join to form the minor calyx
Minor calyxes join to form the major calyx
Major calyxes join to form the renal pelvis which gives rise to the ureter
72
Where is the juxtaglomerular apparatus found?
In the region where part of the distal consulted tubule passes between the fork formed by the afferent and efferent arterioles
73
What are the 2 types of nephron?
Juxtamedullary ~ 20%
Cortical ~80%
74
Describe the blood supply to the cortical nephron?
Blood from the efferent arteriole goes on to form the peritubular capillaries which fully surround the tubule
75
Describe the blood supply to the juxtaglomerular nephron
Blood from the efferent forms a single capillary structure called the vasa recta which follows the path of the tubule
76
What determines an animals percentage of juxtaglomerular nephrons?
Juxtamedullary nephrons produce much more concentrated urine and so the proprtion of juxtamedullary nephrons to cortical nephrons changes depending on environment (E.g. desert animals have more juxtaglomerular nephrons allowing them to concentrate their urine much more
77
How do juxtaglomerular nephrons produce more concentrated urine?
They have a much longer loop of Henle
78
What are the 3 layers of the glomerular wall?
- Capillary endothelial cell layer
- Basement membrane (Basal lamina)
- Podocyte layer
79
What are the 2 specialised regions of the juxtaglomerular apparatus?
Granular cells - Red
Macula densa - Brown
80
What is the function of the granular cells?
Produce and secrete renin
81
What is the function of the macula densa?
Specialised tubular cells which detect NaCl levels present in the tubular fluid as it passes through and can signal the arterioles to contract or relax to regulate blood flow into the glomerulus
82
What is urine?
A modified filtrate of the blood
83
What is reabsorption?
Movement of filtrate components out of the tubule and into the ECF and then blood
84
What is secretion?
Movement of filtrate components out of the blood and ECF and into the renal tubule (Not at the glomerulus)
85
What percentage of plasma entering the glomerulus is filtered?
20%
86
Calculation of rate of excretion
Rate of excretion = Filtration rate + Secretion rate - Reabsorption rate
87
What are the different rates given in the box analogy
FR = Rate at which boxes are put onto the conveyor belt
SR = Rate at which extra boxes are added later
RR = Rate at which boxes are taken off mid-way
ER = Rate at which boxes fall off the conveyor belt
GFR = Rate at which things are loaded onto the conveyor belt
88
What is the rate of filtration?
Mass filtered per unit time
89
Calculation: Rate of filtration of X
[X]plasma x GFR
90
What is the GFR of a healthy adult?
~125ml/min
91
Calculation: Rate of excretion of X
[X]urine x Vu
Where Vu is the urine flow rate
92
What is Vu?
Urine flow rate
93
What is a normal Vu?
~1ml per minte
This can vary based on hydration status (0.3mls/min - 25mls/min)
94
Calculation: Rate of reabsorption of X
Rate of filtration (X) - Rate of excretion (X)
95
What is shown if rate of filtration of X is greater than rate of excretion of X?
There is net reabsorption of X
96
What is shown if rate of filtration of X is less than rate of excretion of X?
There is net secretion of X
97
Calculation: Rate of secretion of X
Rate of secretion (X) - Rate of filtration (X)
98
Calculate Cl- reabsorption or secretion:
[Cl-]plasma = 110 mmol/L
GFR = 120ml/min
[Cl-]urine = 200 mol/L
Vu = 0.001 L/min
Cl- filtered = [Cl-] plasma x GFR
= 110mmol/L x 0.12 L/min
= 13.2 mmol/min
Cl- excreted = [Cl-]urine x Vu
= 200mmol/L x 0.001 L/min
= 0.2 mmol/min
Rate of filtration > Rate of excretion, so net reabsorption of Cl- has occurred
Cl- reabsorption = 13.2 - 0.2 = 13 mmol/min
99
What is the glomerular capillary endothelial wall a barrier to?
RBCs
100
What is the glomerular basement membrane a barrier to?
Large plasma proteins
101
What are the podocyte slits a barrier to?
Plasma proteins
102
What are the 2 forces that drive movement from glomerulus to Bowman's capsule?
Glomerular capillary blood pressure (~55mmHg)
Bowman's capsules oncotic pressure (0mmHg)
103
What are the 2 forces that drive movement from Bowman's capsule to glomerulus?
Bowman's capsule hydrostatic pressure (~15mmHg)
Capillary oncotic pressure (~30mmHg)
104
What is the net filtration pressure moving plasma from the glomerulus to the Bowman's capsule?
(55+0) - (15+30) = 10mmHg
105
Why is there only an oncotic pressure gradient moving from the Bowman's capsules into the capillary?
Many plasma proteins within the blood, no plasma proteins in the Bowman’s capsule, so oncotic pressure only into the Bowman’s capsule
106
What is GFR ?
Rate at which protein-free plasma is filtered from the glomeruli into the Bowman’s capsule per unit time
107
Calculation: GFR
GFR = Kf x Net filtration pressure
Where Kf = Filtration coefficient (How Honey the glomerular membrane is
108
How many times per day is the whole plasma volume filtered?
60-65 times per day
109
What is the major determinant of GFR?
Glomerular capillary fluid blood pressure (BPGC)
110
What can affect filtration coefficient (Kf)?
Drugs
111
What are the 2 pathways of GFR regulation?
Extrinsic regulation
Intrinsic regulation (Autoregulation)
112
What is the main method extrinsic GFR regulation?
Sympathetic control via baroreceptor reflex
113
What are the 2 main methods of intrinsic GFR regulation (Autoregulation)?
Myogenic mechanism
Tubuloglomerular feedback mechanism
114
Describe the extrinsic regulation of GFR in cases of decreased blood volume (E.g. haemorrhage)
Blood volume loss -
Drop in arterial blood pressure
Detected by the aortic and carotid baroreceptors
Sympathetic stimulation causing generalised arteriolar vasoconstriction
Afferent arteriolar vasoconstriction decreases renal blood flow which decreases GFR
This decreases urine volume and helps to retain water to increase blood volume and pressure
115
What is the function of intrinsic regulation of GFR?
Intrinsic mechanisms helps to prevent short term changes in arterial pressure affecting GFR, when it is not needed
For example, when we exercise, blood pressure increases
By the extrinsic mechanism, this would cause vasodilation and therefore increase GFR, expelling more water and more salt, however, during exercise, water and salts are needed
116
What is the myogenic mechanism of autoregulation?
If this smooth muscle of the afferent arteriole is stretched (E.g. by increased arterial pressure), it automatically contracts to regulate the amount of blood flowing into the glomerulus
117
What is the tubuloglomerular feedback mechanism of autoregulation?
The tubuloglomerular feedback mechanism involved the juxtaglomerular apparatus, although the mechanism remains unclear
If GFR rises, more NaCl flows through the distal convoluted tubule, leading to constriction of the afferent arterioles to decrease GFR
This rise of NaCl is detected by the macula densa
118
How would kidney stones affect GFR?
Kidney stone would cause an increase in pressure within the Bowman’s capsule, therefore increasing the Bowman’s capsule fluid pressure (HPBC), and therefore decreasing GFR
119
How would diarrhoea affect GFR?
Diarrhoea would cause dehydration and therefore a decrease in blood pressure, therefore increasing the concentration of plasma proteins in the blood
This increases the capillary oncotic pressure (COPGC) and decreases GFR
120
How would severe burns affect GFR?
Severe burns cause a loss of plasma proteins from the site of injury
This decreases capillary oncotic pressure (COPGC) and therefore increases GFR
121
What is plasma clearance?
This is a measure of how effectively the kidneys can “clean” the blood of a substance
The volume of plasma completely cleared of a substance per minute
122
Calculation: Plasma clearance of substance X
Clearance of substance X = (Rate of excretion of X) ÷ [X] plasma
Clearance X = ([X]urine x Vu) ÷ [X]plasma
123
What value is equal to the rate of clearance of inulin?
GFR
124
What is the normal clearance of glucose by the kidneys
0
It is fully reabsorbed
125
How do the kidneys handle urea?
Urea is a substance that is filtered, partly reabsorbed and is not secreted
126
How are H+ ions handled by the kidneys?
Hydrogen ions are a substance that is filtered, secreted but not reabsorbed
127
How will clearance of urea compare to GFR?
Clearance will be less than GFR as around 50% of the filtered urea is reabsorbed and doesn’t make it into urine
128
How will clearance of H+ ions compare to GFR?
Clearance will be greater than GFR as more hydrogen ions are added in the proximal convoluted tubule
129
Example:
Calculate the clearance of Na+
Vu = 1ml/min
[Na+] urine = 70 mol/L
[Na+] plasma = 140 mol/L
Clearance (X) = ([X]urine x Vu) ÷ [X]plasma
Clearance (Na+) = (70 x 1) ÷ 140
Clearance (Na+) = 0.5 ml/min
0.5 < 125 so there is new reabsorption of Na+ by the kidneys
130
What is renal plasma flow?
Volume of plasma passing through the kidneys per unit time
131
What is the normal renal plasma flow?
650ml/min
132
What molecule is used to estimate renal plasma flow?
Para-amino hipputric acid (PAH)
133
Why can PAH be used to estimate renal plasma flow?
It is freely filtered at the glomerulus and all remaining PAH after this is secreted into the tubule
None is reabsorbed
This means that the clearance of PAH is equal to renal plasma flow
134
What are the 3 criteria that every marker must follow?
A marker must be:
- Non-toxic
- Inert (Not-metabolised by the kidney)
- Easy to measure
135
What characteristics must a GFR marker have?
Freely filtered
Not secreted
Not reabsorbed
136
What characteristic must a renal plasma flow marker have?
Freely filtered
Completely secreted
Not reabsorbed
137
What is filtration fraction?
The fraction of plasma flowing through the glomeruli that is filtered into the tubules (Bowman’s capsule)
138
Calculation: Filtration fraction
Filtration fraction = GFR ÷ Renal plasma flow
= 125/650
= 0.19
≈ 20%
139
What is renal blood flow?
The volume of blood passing through the kidneys per unit time
140
Calculation: Renal blood flow
RBF = RPF x (1 ÷ (1-haematocrit))
= 650 x 1.85
≈ 1200ml/min
141
What percentage of cardiac output do the kidneys receive?
~25%
142
What makes reabsorption so specific?
The expression of a number of transport proteins and channels
143
Where in the nephron does the majority of reabsorption occur?
Proximal convoluted tubule (~2/3rds)
144
Describe the tonicity and osmolarity of the reabsorption fluid compared to the blood into which it is returning
Isotonic
It has the same osmolarity as the blood (~300mosmol/L)
145
What are some molecules reabsorbed in the proximal tubule?
- Sugars
- Amino acids
- Phosphate
- Sulphate
- Lactate
146
What are some molecules secreted in the proximal tubule?
- H+
- Hippurates
- Neurotransmitters
- Bile pigments
- Uric acids
- Drugs
- Toxins
147
What are the 2 major routes of reabsorption in the PCT?
Trans-cellular route - Through cells via transporters or diffusion
Para-cellular route - Between cells
148
What are the 5 main transport mechanisms of reabsorption?
Primary active transport
Secondary active transport (Co-transport)
Facilitated diffusion
Diffusion through channels
Diffusion through lip bilayer
149
What is primary active transport?
ATP needed to operate carriers to move a substrate against it’s concentration gradient
150
What is secondary active transport (Co-transport)
Carrier molecule is transported, coupled to the concentration gradient of an ion (Usually Na+)
151
What is facilitated diffusion?
Passive carrier-mediated transport of a substance down its concentration gradient
152
Where in the nephron is Na+ reabsorbed?
All regions except the descending limb of the loop of Henle
153
Describe the reabsorption of NaCl in the PCT
Na+ pumped into the cell by 3 different transporters
Na+ pumped out of the cell by the Na+/K+ pump
Increased [Na+] in ECF increases osmolarity, so water and Cl- move via the paracellular route into the ECF
154
What are the 3 luminal Na+ transporters involved in NaCl reabsorption?
- Na+ - Glucose co-transporter
- Na+ - Amino acid co-transporter
- Na+ - H+ counter-transporter
155
How do NaCl and water enter the capillary?
Aided by the oncotic drag of the plasma, due to the presence of plasma proteins (These are concentrated in the blood due to previous filtration, causing the oncotic drag)
156
Describe the reabsorption of glucose in the PCT
Glucose enters the cell via the Na+/Glucose co-transporter (Na+ gradient maintained by Na+/K+pump)
Glucose leaves the cell via facilitative transporters
(This also draws in para-cellular water)
157
Describe the trend in rate of filtration of substance X compared to plasma concentration and GFR?
As [X]pasma rises, rate of filtration rises proportionally
158
Describe the trend in rate of reabsorption of substance X compared to rate of filtration?
As [X]plasma rises, rate of filtration rises proportionally
Rate of reabsorption rises initially, however, it then reaches the transport maximum, when rate of reabsorption plateaus
159
What is the transport maximum?
The maximum rate at which a substance is reabsorbed
160
Give a clinical example of when transport maximum is exceeded?
In diabetes, [Glucose]plasma causes an increase in rate of filtration of glucose above the transport maximum, so not all glucose is reabsorbed and so is excreted
161
Where does the loop of Henle arise?
It arises at the cortico-medullary junction
162
What is the main function of the loop of Henle?
It functions to generate the cortico-medullary solute concentration gradient
163
What is the cortico-medullary solute concentration gradient?
This is the progressively increasing osmolarity of the ECF passing from the cortex to the medulla
164
What is the function of the cortico-medullary solute concentration gradient?
This enables the formation of hypertonic urine
165
Describe the transport mechanisms of the descending limb of the loop of Henle
This segment is highly permeable to water, but does no reabsorb NaCl
166
Describe the transport mechanisms of the ascending limb of the loop of Henle
Along the entire length of the ascending limb, Na+ and Cl- (NaCl) is reabsorbed from the tubular fluid, into the interstitial fluid
The ascending limb is relatively impermeable to water, so little water follows the NaCl as it is reabsorbed (Paracellular water movement is blocked by tight gap junctions)
167
What are the 2 parts of the descending limb of the loop of Henle?
Thick upper (active transport)
Thin lower (Passive)
168
Describe the transport mechanism of the full loop of Henle
1. Tubular fluid passes through the descending limb
169
