Filtration by the Glomerulus Flashcards
1
Q
How is blood supplied to the kidney?
A
Via the renal artery
2
Q
What divisions does the renal artery undergo?
A
Renal artery -> Segmental arteries -> Interlobar arteries -> Arcuate arteries -> Interlobular arteries -> Afferent arterioles
3
Q
What do the afferent arterioles each do?
A
Deliver blood to a single nephron
4
Q
How does the diameter of each afferent arteriole differ from the diameter of the associated efferent arteriole?
A
It is slightly greater
5
Q
What is the result of the diameter difference between the afferent and efferent arteriole?
A
It increases the pressure of the blood in the glomerulus
6
Q
What is the result of the increased pressure of the blood inside the glomerulus
A
The increased hydrostatic pressure helps to force components out of the blood in the glomerular capillaries
7
Q
What components are forced out of the blood by the increase in hydrostatic pressure in the glomerulus?
A
- Most of the water
- Most/all of the salts
- Most/all of the glucose
- Most/all of the urea
8
Q
What % of blood delivered to the glomerulus is actually filtered?
A
20%
9
Q
How does the 80% of delivered blood that isn’t filtered exit?
A
Via the efferent arteriole
10
Q
What allows the water, salts, glucose, and urea to be filtered out of the blood inside the glomerulus?
A
They are relatively small particles
11
Q
What components cannot be filtered out of the blood in the glomerulus as they are too large?
A
- RBCs
- Plasma proteins
12
Q
What is the size limit for filtration in the glomerulus?
A
Molecular weight 5,200, or an effective molecular radius of 1.48nm
13
Q
Other than size, what makes it hard for proteins to be filtered in the glomerulus?
A
The basement membrane and podocytes glycocalyx have negatively charged glycoproteins, which repel protein movement
14
Q
What happens to the water and solutes that have been forced out of the glomerular capillaries?
A
They pass into Bowman’s space
15
Q
What are the water and solutes that pass into the Bowman’s space called?
A
The glomerular filtrate, or the ultrafiltrate
16
Q
What does the filtration barrier consist of?
A
- Capillary endothelium
- Basement membrane
- Podocyte layer
17
Q
What can pass through the capillary endothelium?
A
- Water
- Salts
- Glucose
18
Q
Where does filtrate move when passing the capillary endothelium?
A
Between cells
19
Q
What is the filtration barrier basement membrane?
A
An acellular gelatinous layer of collagen/glycoproteins
20
Q
What is the filtration barrier basement membrane permeable to?
A
Small proteins
21
Q
What is the purpose of the glycoproteins in the filtration barrier basement membrane?
A
They have a negative charge and so repel protein movement
22
Q
What happens in the podocyte layer?
A
Pseudopodia interdigitate to form filtration slits
23
Q
Label this diagram
A
- A - Capillary plasma
- B - Capillary endothelial cell
- C - Basement membrane
- D - Pedicel
- E - Filtration slit
- F - Podocyte
- G - Fenestration
24
Q
What physical forces is plasma filration due to?
A
- Hydrostatic pressure in the capillary (PGC)
- Hydrostatic pressure in the Bowman’s capsule (PBC)
- Osmotic pressure difference between the capillary and tubular lumen (πGC)
25
Which of the physical forces causing plasma filtration can be regulated?
Hydrostatic pressure in the capillary
26
What is the net filtration pressure?
10mmHg
27
What is the hydrostatic pressure in the plasma?
50mmHg
28
Does the hydrostatic pressure in the plasma favour or oppose filtration?
Favour
29
What is the hydrostatic pressure in the tubule (Bowman's capsule)?
15mmHg
30
Does the hydrostatic pressure in the tubule favour or oppose filtration?
Oppose
31
What is the osmotic pressure in the glomerulus?
25mmHg
32
Does the osmotic pressure in the glomerulus favour or oppose filtration?
Oppose
33
Draw a diagram illustrating how the net filtration pressure is established
34
What is the effect of a molecules negative charge on filtration?
Negative charge repels, so more difficult to get through
35
What is the effect of a molecules positive charge on filtration?
Allows slightly bigger molecules through
36
What happens to the negative charge on the filtration barrier in many disease processes?
It is lost
37
What is the result of the loss of the negative charge on the filtration barrier in disease?
Proteins are more readily filtered
38
What is the clinical condition where proteins are more readily filtered?
Proteinuria
39
What is the main clinical symptom of proteinuria?
Protein in the urine
40
What % of the glomerular filtrate leaves the body?
~1%
41
What happens to the glomerular filtrate that doesn't leave the body?
It is reabsorbed into the blood as it passes through renal tubules
42
What is the process of reabsorbing glomerular filtrate into the blood called?
Tubular reabsorption
43
By what mechanisms does tubular reabsorption occur?
* Osmosis
* Diffusion
* Active transport
44
Why is tubular reabsorption called **re**absorption, not absorption?
As these substances have already been absorbed once, *particularly in the intestines*
45
What is the nature of reabsorption in the PCT?
It is isosmotic
46
What is reabsorption in the PCT driven by?
Sodium uptake
47
What is required to maintain electro-neutrality during reabsorption in the PCT?
Other ions accompany sodium
48
What ions accompany sodium during reabsorption in the PCT to maintain electro-neutrality
* Chloride
* Bicarbonate
49
What % of filtered water is reabsorbed?
99%
50
What % of filtered sodium is reabsorbed?
99.5%
51
What % of filtered glucose is reabsorped?
100%
52
What % of filtered urea is reabsorbed?
50%
53
Where do solutes move from the tubular lumen?
To the interstitum, then to the capillaries
54
What are the possible types of reabsorption?
* Transcellular
Paracellular
55
What is meant by paracellular reabsorption?
Around cells through tight junctions
56
Describe the process of tubular reabsorption of Na+
1. Na+ is pumped out of tubular cells across the basolateral membrane by 3Na-2K-ATPase
2. Na+ moves across the apical (luminal) membrane down its concentration gradient.
3. Water moves down the osmotic gradient created by reabsorption of Na+
57
What does the movement of Na+ across the apical membrane utilise?
A membrane transporter or channel on the apical membrane
58
Draw a diagram illustrating the tubular reabsorption of Na+
59
What does secretion in the kidney provide?
A second route, *other than glomerular filtration,* for solutes to enter the tubular fluid
60
Why is secretion in the kidney useful?
As only 20% of the plasma is filtered each time the blood passes through the kidney
61
What does secretion in the kidney help maintain?
The blood pH
62
What is the range of normal blood pH?
7.38-7.42
63
What substances are secreted into tubular fluid?
* Protons (H+)
* Potassium (K+)
* Ammonium ions (NH4+)
* Creatinine
* Urea
* Some hormones
* Some drugs
64
Give an example of a drug that is secreted into the tubular fluid
Penicillin
65
What is the model for organic cation (OC+) secretion in the PCT?
1. **Entry by passive carrier -** Mediated diffusion across the basolateral membrane down favourable concentration and electrical gradients, created by the 3Na-2K-ATPase pump
2. **Secretion into the lumen -** H+-OC+ exchanger that is driven by the H+ gradient created by the Na+-H+-Antiporter
66
Draw a diagram illustrating the model for organic cation secretion in the PCT
67
What do different segments of the tubule have?
Different types of Na+ transporters and channels in the apical membrane
68
What does the different types of Na+ transporters and channels in different segments of the tubule allow?
Na+ to be the driving force for reabsorption, using the concentration gradient set up by 3Na-2K-ATPase *(active transport)*
69
What Na+ transporters/channels are found in the proximal tubule?
* Na-H antiporter
* Na-Glucose symporter (SGLUT)
70
What Na+ transporters/channels are found in the Loop of Henle?
Na-K 2Cl symporter
71
What Na+ transporters/channels are found in the early distal tubule?
Na-Cl symporter
72
What Na+ transporters/channels are found in the later distal tubule and collecting duct?
ENaC *(epithelial Na-Cl)*
73
Label this diagram
* A - Interlobular arteries
* B - Afferent arterioles
* C - Glomerular capillaries
* D - Efferent arterioles
* E - Glomerular capsule
* F - Rest of renal tubule
* G - Peritubular capillaries
* H - To interlobular veins
* I - Urine
74
In what direction does Na+ travel down its concentration gradient in the kidney?
From the tubule lumen into the intersticium
75
What sets up the Na+ concentration gradient between the tubule and the intersticium?
3Na-3K-ATPase
76
What does the transport of Na+ down its concentration gradient from the tubule lumen into the intersticium often occur with the help of?
A symporter
77
What is the importance of the mechanism by which Na+ travels from the tubule lumen into the intersticium?
It is the mechanism by which the body reabsorbs glucose, amino acids, water soluble vitamins (B & C), lactate acetate, ketones, and other Krebs cycle intermediates
78
What happens one glucose, amino acids, water soluble vitamins (B & C), lactate acetate, ketones, and other Krebs cycle intermediates have been reabsorbed?
They then move on through cells via diffusion and/or active transport
79
How is glucose reabsorbed in the PCT?
Using the Na-glucose symporter, SGLUT
80
What does SGLUT do?
Moves glucose against its concentration gradient into the tubule cells
81
What happens once SGLUT has moved glucose into the tubule cells?
Glucose moves out of the tubule cell on the basolateral side by facilitated diffusion
82
How much glucose is normally reabsorbed?
100%
83
What limits the amount of glucose that can be reabsobed?
The system has a maximum capacity, or **transport maximum (Tm)**
84
What happens if the plasma concentration of glucose exceeds the Tm?
The rest spills over into the urine
85
What happens if excess glucose spills over into the urine?
Water follows into the urine, causing frequent urination
86
What is the clinical symptom of frequent urination called?
Polyuria
87
What is the renal threshold for glucose?
200mg/100ml
88
What is meant by clearance?
The volume of plasma from which a substance can be completely cleared to urine per unit time
89
What is the input to the kidney?
The renal artery
90
What are the possible outputs from the kidney?
* The renal vein
* The ureter
91
What must happen if a substance is not metabolised or synthesised in the kidney?
An equal amount must leave in the urine and the renal venous blood
92
How can clearance be calculated?
Clearance = (Amount in urine x Urine flow rate) / Arterial Plasma Concentration
93
What is meant by glomerular filtration rate (GFR)?
The volume of plasma from which any substance is completely removed by the kidney in a given amount of time *(usually 1 minute)*
94
What is GFR a measure of?
The kidney's ability to filter a substance, *thus overall function*
95
What is GFR an indication of?
How well the kidney works
96
What does a fall in GFR generally mean?
Kidney disease is progressing
97
What must happen to measure GFR?
A substance must be freely filtered across the glomerulus
98
What is meant by a substance being freely filtered across the glomerulus?
It must pass directly into the urine- it must not be reabsorbed, secreted, or metabolised by the cells of the nephron
99
Give two examples of substances that can be used to calculate GFR
* Creatinine
* Inulin
100
What equation is used to calculated GFR?
(Amount in urine x urine flow rate) / Arterial plasma concentration
101
What is the normal GFR for males?
115-125ml/min
102
What is the normal GFR for women?
90-100ml/min
103
How much blood does the kidney recieve a minute?
About 1.1L
104
What % of the blood the kidney receives is RBCs, and what % is plasma?
* 45% RBCs
* 55% plasma
105
What is renal plasma flow to the kidney?
605ml/min of plasma
## Footnote
*(55% of 1.1L)*
106
What is meant by filtration fraction?
The proportion of a substance that is actually filtered
107
How is filtration fraction calculated?
Filtration fraction = Glomerular filtration rate / renal plasma flow
108
What is the normal filtration fraction in healthy adults?
About 20%
109
How is the normal filtration fraction of 20% worked out?
If renal plasma blow is 605ml/min, and 20% of all plasma is filtered, 125ml is filtered through into Bowman's space- this is the **normal GFR**, *and 480ml passes through into peritubular capillaries*
## Footnote
**125/605=20.8%**
110
What is the purpose of autoregulation of renal blood flow?
Auto-regulatory mechanisms keep the GFR within normal limits when arterial BP is within physiological limits
111
What is the result of the myogenic response to rises in arterial BP?
Afferent arteriole constriction
112
What is the result of the myogenic response to falls in arterial BP?
Afferent arteriole dilation
113
Draw a graph showing the relationship between renal blood flow and glomerular filtration rate
114
What can changes in GFR result in?
Changes in tubular flow rate
115
What is the result of changes in tubular flow rate?
Change in the amount of NaCl that reaches the distal tubule
116
What responds to changes in the amount of NaCl reaching the distal tubule?
Macula densa cells
117
What response is needed if NaCl reaching the distal tubule increases?
GFR needs to decrease
118
What response is initiated if NaCl reaching the distal tubule increases?
Adenosine is released, causing vasoconstriction of afferent arteriole
119
What response is needed if NaCl reaching distal tubule decreases?
GFR needs to increase
120
What response is initiated if NaCl reaching distal tubule decreases?
Prostaglandins released, causing vasodilation of afferent arteriole
121
Draw a diagram illustrating the potential ways to modify the resistance in the glomerular capillay
122
What is meant by general overflow aminoaciduria?
All amino acids are present in the urine
123
What is general overflow aminoaciduria normally due to?
Inadequate deamination in the liver, or increased GFR
124
When is general overflow aminoaciduria often seen?
In early pregnancy
125
What is meant by specific overflow aminoaciduria?
Only a specific AA is present in the urine
126
What is specific overflow aminoaciduria usually due to?
Genetic inability to break down one AA
127
Give an example of a condition where the patient has a genetic inability to break down one AA
PKU
128
What happens in PKU?
There is a lack of phenylalanine hydroxylase, so phenylalanine can't be broken down
129
What is renal aminoaciduria mainly confined to?
The dibasic acid
130
What is renal aminoaciduria due to?
A genetically determined lack of the specific transport protein(s)
131
Why is cysteine of importance when considering renal aminoaciduria?
It is an abnormally insoluble amino acid, *especially in acidic urine*
132
What may cystinuria be associated with?
Stone formation
