Gene models & nephron function Flashcards
1
Q
What % of plasma is filtered into Bowman’s capsule?
A
20%
2
Q
What is tubular secretion?
A
movement from peritubular capillary
3
Q
What is the diameter of the glomerulus?
A
20um
4
Q
How much plasma is filtered per day?
A
180 litres/day filtrate
5
Q
Describe the level of energy needed for glomerular filtration to take place
A
High levels of energy
6
Q
What arteriole carries blood into the glomerular capillaries?
A
afferent arteriole
7
Q
What arteriole carries blood out of the glomerular capillaries?
A
efferent arteriole
8
Q
What does the glomerulus permit across its membrane?
A
H20 & small molecules
9
Q
What does the glomerulus restricts across its membrane?
A
blood cells & proteins
10
Q
What is ultra-filtrate composed of?
A
- consists of protein free plasma
- 1% protein filtered (albumin) - usually reabsorbed by the proximal tubule
11
Q
What can proteins in urine be a sign of?
A
UTI
12
Q
What is movement from the lumen of the nephron into peritubular called?
A
transcellular reabsorption
13
Q
What is movement from the peritubular capillary into the lumen of tubule called?
A
transcellular secretion
14
Q
What is movement in both directions between the lumen of tubule & peritubular capillary called?
A
Paracellular secretion or reabsorption
15
Q
What is transcellular reabsorption called?
A
transport using transport proteins, transpiring ion solutes + water into cell across membrane
16
Q
What does paracellular movement move?
A
Between cell
17
Q
How many genes does the human genome have?
A
33,000 genes
18
Q
How many renal genes does a human have?
A
Several hundred
19
Q
How much reabsorption takes place in the proximal tubule?
A
- 70% (H2O & Na+)
- approx 100% glucose & amino acids
- 90% HCO3 (bicarbonate)
- high levels of mitochondria to allow energy-requiring processes to occur
20
Q
What ATPase is found on the proximal tubule basolateral membrane?
A
sodium-potassium ATPase
21
Q
What membrane are potassium channels found on in the basolateral membrane?
A
basolateral
22
Q
Describe the intracellular sodium concentration in the proximal tubule
A
low
23
Q
What cotransporters are involved on the apical surface of the proximal tubule involved in the movement pf sodium & glucose into the cell?
A
SGL T1 & SGL T2
24
Q
What is the sodium phosphate cotransporter (NaPiII) involved in?
A
The movement of phosphate into cell
25
What are the results of NaPiII knockout mouse phenotype?
- Less Pi reabsorption
- More lost in urine
- Issues renal mineralisation
(renal mineralisation - renal stone/crystal formation)
26
What is the importance of phosphate?
- bone formation
- used for ATP
27
What staining is used to see the NaPiIIa knockout in a mouse?
Von Kossa staining - lots of dark-stained sports indication of mineralisation
28
What occurs as a result of low intracellular sodium concentration?
creates an electrochemical gradient for cotransporter to move sodium into the cell & hydrogen out of the cell
29
What happens to the hydrogen once it has left the cell?
it binds to HCO3 (bicarbonate), forming H2CO3 (carbonic acid). Carbon anhydrase then moves CO2 & H20 into the cell. Intracellular anhydrase then moves bicarbonate out of the cell via the basolateral exit
30
Why is reabsorption of bicarbonate important?
regulates the pH of the body
31
What is the effect of knocking out the NHE3 gene?
struggle to reabsorb plasma bicarbonate (HCO3), and a lower pH due to lack of pH regulation
32
What is the relationship between plasma glucose concentration & plasma glucose reabsorption?
linear relationship
33
When does plasma glucose concentration not have a linear relationship with plasma glucose reabsorption?
when there is no more free carriers for reabsorption
34
What is the renal threshold?
concentration of a substance dissolved in the blood above which the kidneys begin to remove it into the urine
35
What is the inherited disease given to those whose sodium-glucose carriers don't work?
diabetes
36
What 2 systems are used to remove substances from the proximal tubule?
organic cations & organic anions
37
What is the function of the Loop of Henle?
- concentration of the urine
- reabsorption of Na+, Cl-, H2O
- reabsorption of Ca2+ & Mg2+
- site of action of loop diuretics
38
What are the 3 parts of the loop of Henle?
- descending limb
- thin ascending limb
- thick ascending limb
39
What size diameter is the descending limb?
thin
40
What leaves in the thin descending limb?
water
41
what leaves in the ascending limb?
sodium & chloride
42
What is the purpose for water leaving in the descending limb & sodium & chloride leaving in the thin ascending limb?
creates osmotic gradient which allows for water reabsorption
43
What leaves the thick ascending limb?
1 sodium, 1 potassium, 2 chloride ions released into the intracellular compartment
44
How does sodium leave the body?
via a sodium ATPase
45
What is needed for the CLCK channel to reabsorb chloride?
Barttin (beta subunit)
46
What does ROMK allow?
potassium reabsorption
47
What does Bartter's syndrome lead to?
problem with sodium & chloride reabsorption
- hypotension (due to reduced ECF)
- kypokalaemia
- metabolic alkalosis
- hypercalciuria (calcium in urine)
- nephrocalcinosis - kidney stones
48
What is the biological effect of inability to produce barttin?
faulty CLCK
49
What do diuretics do?
increase urine, therefore reducing high blood pressure
50
What are people with Barter's syndrome unlikely to experience?
hypertension
51
What occurs in the early distal tubule?
- reabsorption of Na + Cl
- reabsorption of Mg2+
- sensitive to thiazine diuretics
52
What is Gitelman's syndrome?
salt wasting & polyuria (lots of urine)
- hypotension
- hypokalaemia
- metabolic alkalosis
- hypocalciuria
53
What is the role of NCC?
transport of sodium & chloride into early distal tubule, no potassium
54
What occurs in the late distal tubule?
- increasing the concentration of the urine
- reabsorption of Na+ & H2O
- secretion K+ & H+
55
What 2 types of cell is the late distal tubule & cortical collecting duct?
principal & intercalated cells
56
What occurs in principal cells in the late distal tubule?
- Na & H2O reabsorption
- K+ & H+ secretion
57
What occurs in intercalated cells in the late distal tubule?
a (alpha) IC & b (beta) IC
IC = intercalated
- different levels of A&B cells lead to different levels of hydrogen & bicarbonate secretion & absorption
58
What is the ENaC channel in principal cells?
Epithelium sodium channel
59
What does ROMK do in principal cells?
secretion of potassium, which is driven by reabsorption of sodium
60
What does aquaporin 2 do?
reabsorb water
61
What is lost in the urine?
potassium
62
What is the role of the ATPase?
- maintain negative membrane potential
- maintain low intracellular concentration
63
What diseases can be caused by principal cell?
diabetes insipidus - AQP2
Liddle's syndrome - ENaC
64
What is the effect of amiloride?
- to increase fluid loss - block Na+ channel = lower H2O = decrease blood pressure
65
What is lost in alpha intercalated cells?
Hydrogen cells (using ATP)
66
What does the AE1 (anion exchange protein 1) cotransporter do?
move chloride (that has been moved out) into cell, while bicarbonate is moved out
67
What happens in B intercalated cells?
AE1 cotransporter on apical membrane
- hydrogen removed via ATP in basolateral membrane
68
What is the difference between an alpha intercalated cells & beta intercalated cells?
alpha - hydrogen removed from apical & bicarbonate on basolateral
beta - hydrogen removed on basolateral & bicarbonate on apical membrane
69
What will more b cells being present lead to?
more hydrogen ion being retained
70
What will more a cells being present lead to?
more hydrogen excretion
71
What occurs in the medullary collecting duct?
- Low Na+ permeability
- High H20 & urea permeability in the presence of antidiuretic hormone
72
What is acute renal failure?
reversible impaired fluid & electrolyte homeostasis
- accumulation nitrogenous waste
- lasts 1 week
73
What are the general symptoms of renal failure?
- hypervolaemia
- hyperkalaemia
- acidosis
- high urea/creatinine
74
What is hypervolaemia?
lack of urine due to a fall in GFR
75
What is hyperkalaemia?
lack of K+ secretion
76
What is acidosis, and its consequence?
acidic bodily fluids - leads to depressed central nervous system - stops function of neurones
77
78
What can high urea/creatinine lead to?
impaired mental function, nausea, vomiting
79
What is oliguria?
Fall in GFR
80
What is a pre-renal cause of acute renal failure?
Rhabdomyolysis - release myoglobin from damaged muscle - toxic effects on kidney tubules
81
What is a renal cause of acute renal failure?
High K+ lack of defection & release from damaged cells - tachycardia
82
What can a lack of bicarbonate lead to?
acidosis
83
What is used to hyperkalaemia?
IV saline
84
What is used to treat acidosis?
increase in bicarbonate
85
What is antidiuretic hormone?
vasopressin
86
Where is ADH released from?
posterior pituitary gland
87
Where do axons move down?
pituitary stalk
88
What type of cells fire action potentials?
neuronal cells
89
What does ADH do?
regulates body fluid osmolality - conserves H2O
90
What happens if there is an increase in ADH?
there is an increase in body fluid
91
What happens if there is a decrease in ADH?
there is a decrease in body fluid
92
Other than water, what else does ADH regulate?
sodium concentration
93
What detects water levels?
hypothalamic osmoreceptors
94
What level of water change do hypothalamic osmoreceptors detect?
3 mosmol/kg H2O
95
What occurs if the supra-optic & paraventricular nuclei is stimulated?
1. Release ADH from posterior pituitary
2. feeling of thirst
96
What occurs following activation of osmoreceptors?
activation of neuronal cells. This leads to an increase in ADH released
97
What occurs if ADH levels is increased?
increase osmolality plasma
98
What does ecstasy promote?
water retention
99
What occurs if ADH levels is decreased?
decrease in osmolality plasma
100
Describe the effect of alcohol on ADH release
inhibits the release of ADH - high level of water released
101
What is the normal plasma ADH pg/ml?
4
102
What is the normal plasma osmolality mosm/kgH2O?
285
103
How is an osmotic force created on principal cells?
there are aquaporins present on both the apical & basolateral membrane
104
What is the V2 receptor?
receptor for ADH. This activates protein kinase A (PKA), which leads to high levels of aquaporin 2 being inserted into the membrane.
105
What happens if there are a high number of aquaporin 2 in the membrane?
high number of aquaporin 2 = high number of channels = high level of water absorption
106
Are aquaporins 3+4 regulated ADH?
aquaporin 2
107
What is the net effect of ADH?
- increase in H2O reabsorption
- fall in body fluid osmolality
108
How many litres of dilute urine do people with diabetes insipidus excrete a day?
23
109
What is diabetes insipidus caused by?
no ADH released - defect in secretory neurones of ADH
110
What can treat diabetes insipidus?
nasal spray - desmopressin
111
What is nephrogenic diabetes insipidus?
- defect in V2 receptor
- H2O channel defect
112
Where is aldosterone released from?
cortex of the adrenal gland -zona glomerulosa layer
113
What does mineralocirticoid do?
regulates plasma Na+, K+ & body fluid volume
114
When is aldosterone released?
released in response to:
- increase in plasma K+ - 01mM
- decrease plasma Na+ - minor concentration maintained by osmoregulation
- decrease volume - via renin-angiotensin
115
What structures does aldosterone act on?
- late distal tubule
- collecting duct
116
What are the causes of aldosterone release?
- increased reabsorption of Na+
- increased reabsorption of H2O
- increased secretion of K+ & H+
116
What is the result of aldosterone on ENaC?
aldosterone puts more channels in the membrane & makes the channels stay open for longer
117
What is a Pseudohypoaldosteronism?
- salt loss but high aldosterone
- loss response to aldosterone
- mineralocorticoid receptor problem
118
What does renin-angiotensin regulate?
body fluid volume, plasma Na & K
119
Where is Renin released from?
juxtaglomerular apparatus (JGA)
120
What type of cells within the juxtaglomerular apparatus (JGA)?
granular cells
121
What triggers the release of angiotensinogen?
renin
122
What is necessary to allow the conversion from angiotensin 1 to angiotensin 2?
ACE (angiotensin cascade enzyme)
123
What does angiotensin 2 release?
aldosterone
124
Describe what would occur if you ingested salt?
- increase in plasma Na+ & H2O moves out of ICF
- increase in extracellular fluid volume & an increase osmolality plasma
125
How does a decrease in ECFV occur?
- decrease aldosterone
- increase in loss of Na+
- increase in loss of H2O
- decrease in ECFV
126
How does an increase in ECFV occur?
- increase in ADH
- increase in absorption of H2O
- decrease in osmolality
- increase in extracellular fluid volume
127
Why is extracellular volume key in integration?
blood pressure is most important over water content
