REN L10-L20 Flashcards
1
Q
What osmolality are all bodily fluids except the interstitial space of the renal medulla? (L10 Osmoregulation)
A
285mOsm/kg
2
Q
Osmolality is detected by which part of the brain? L10
A
Anterioventral third ventricle (AV3V) region
3
Q
Where do AV3V neurones project to? L10
A
Supraoptic and paraventricular parts of the hypothalamus
4
Q
What is released from the hypothalamus in response to an increase in osmolality? L10
A
ADH
5
Q
What is co-released with ADH as its co-peptide? L10
A
Neurophysin
6
Q
What receptors does ADH act upon and where are they? L10
A
V2 receptors on the basolateral membrane of the cortical collecting duct
7
Q
Activation of V2 receptors causes what? L10
A
AQP2 receptor exocytosis
8
Q
What effect does oxytocin have at V2 receptors? L10
A
It is an agonist
9
Q
If maximum ADH was released what volume of urine would be produced per day and at what osmolality? L10
A
300ml at 1400mOsm
10
Q
If no ADH was released what volume of urine would be produced per day and at what osmolality? L10
A
2.5L at 60mOsm
11
Q
What are symptoms of the hyperosmolar hyperglycaemic state seen in diabetes mellitus? L10
A
Altered mental status, seizures and other neurological signs
12
Q
Give example of ADH analogue given in diabetes insipidus. L10
A
Desmopressin
13
Q
Where are juxtaglomerular cells, and what do they release? (L11 Volume regulation)
A
In the wall of afferent arterioles in the kidney
They release renin
14
Q
What type of cell are juxtaglomerular cells? L11
A
Smooth muscle cells
15
Q
What is the thickening of the early distal tubule in the kidney? L11
A
Macula densa
16
Q
What is the function of the macula densa? L11
A
They sense changes in NaCl
17
Q
What happens in the macula densa senses a fall in NaCl? L11
A
Causes vasodilation of afferent arterioles, increasing GFR
Stimulates renin release from the JG cells
18
Q
What is the aim of the RAA system? L11
A
To increase effective circulating volume
19
Q
Where is angiotensinogen produced? L11
A
Liver
20
Q
What converts angiotensinogen into angiotensin I? L11
A
Renin
21
Q
What does angiotensin-converting enzyme do and where is it mainly found? L11
A
Converts angiotensin I to angiotensin II
In the lungs
22
Q
What are four effects of angiotensin II? L11
A
Efferent arteriole vasoconstriction
Increases Na+ reabsorption in proximal tubule
Aldosterone release
ADH release
23
Q
Where is aldosterone released from? L11
A
Adrenal cortex
24
Q
What receptor does angiotensin II act upon? L11
A
AT1 receptors
25
How is renin release stimulated in haemorrhage? L11
Low cardiac output and low circulating volume leads to a lower BP; the sympathetic nervous system increases its activity and renin is released. Also the afferent arteriole senses the BP drop by decreased wall tension and hence releases renin.
26
What are the three actions of activating sympathetic innervation of the afferent arteriole? L11
Vasoconstriction upstream of JG cells causes a further fall in pressure sensed by the cells
Direct stimulation of renin release by direct innervation
Afferent arteriole vasoconstriction drops glomerular hydrostatic pressure hence lowering GFR
27
Name some stimuli for ADH release. L11
Activation of baro-reflex
Angiotensin II action
Nicotine
Increased osmolality
28
What effect on sodium can ADH have? L11
Hyponatraemia; water is retained to maintain circulating volume but this does not retain Na+
29
Name stimuli that suppress ADH release. L11
Alcohol
Decreased osmolality
Increased circulating volume
30
Define effective circulating volume. L11
The component of blood that is perfusing the tissues (may be different from total blood volume e.g. in heart failure)
31
What are three ways that a decreased effective circulating volume can stimulate renin release? L11
Sympathetic activation: from baro-reflex activation
Decreased wall tension in aff. arteriole: lowered renal perfusion pressure
Macula Densa mechanism: less NaCl delivered to distal tubule
32
What is normal arterial pH? (L12 Acid-base regulation)
7.4
33
What is normal venous pH? L12
7.35
34
What is normal arterial PCO2? L12
40mmHg or 5.3kPa
35
What is normal venous PCO2? L12
46mmHg or 6kPa
36
When does excess H+ production occur? L12
ATP hydrolysis
Ketone production
Anaerobic respiration
Acid ingestion
37
How is excess H+ removed? L12
Reacts with bicarbonate producing CO2 which can be exhaled. The kidney reabsorbs bicarbonate to replace the losses elsewhere.
38
Name the enzyme that catalyses HCO3- + H+ >>> H20 + CO2. L12
Carbonic anhydrase
39
Where is 90% of bicarbonate reabsorbed? L12
Proximal tubule
40
How does the bicarbonate cross the basolateral membrane? L12
Na+/HCO3- co-transporter
41
What happens if there is still excess H+ in the filtrate? L12
Buffered with hydrogen phosphate
42
What is the name of the cells that secrete H+ ions in the distal tubule and why are they needed? L12
Intercalated cells; have to secrete the H+ as it is against a much larger conc.grad.
43
How is ammonium produced in the proximal tubule? L12
Deamination of glutamine
44
What happens to the pH along the nephron? L12
Becomes progressively acidic, can be as low as 4.5 in the collecting duct (urine usually acidic)
45
What is a typical cause of respiratory acidosis? L12
Hypoventilation
46
How does the ____ compensate respiratory acidosis? L12
Kidney; it increases bicarbonate production to return pH to normal
47
What is a typical cause of metabolic acidosis? L12
Renal failure, keto-acidosis, lactic acidosis
48
How does the ____ compensate metabolic acidosis? L12
Lungs; increase ventilation rate
49
What is a typical cause of respiratory alkalosis? L12
Hyperventilation
50
How does the ____ compensate respiratory alkalosis? L12
Kidney; it decreases bicarbonate production to return pH to normal
51
What is a typical cause of metabolic alkalosis? L12
Vomiting
52
How does the ____ compensate metabolic alkalosis? L12
Lungs; decrease ventilation rate
53
Factors affecting serum creatinine. (L13 CKD)
Age, gender, ethnicity, body mass
54
What is used to calculate eGFR? L13
Creatinine, age, gender, ethnicity
55
What is the eGFR for end-stage (stage 5) kidney disease? L13
<15ml/min
56
What is normal eGFR? L13
>90ml/min
57
Name some causes of CKD. L13
Infectious diseases e.g. TB, HIV
Systemic diseases e.g. DM, hypertension
Genetic diseases e.g. polycystic kidneys
Obstruction e.g. tumour, stones, fibrosis
58
Describe the pathology of CKD. L13
Thickening of the basement membrane
Mesangial expansion
Glomerulosclerosis
59
State and explain the reasons for why there are CKD complications. L13
Anaemia; decreased EPO production
Hypertension; volume expansion, Na+ retention, RAS activation
Bone disease; disturbed calcium-phosphate homeostasis
Secondary hyperparathyroidism; from increased PTH
Abnormal drug handling; failure to excrete
60
What can be the effects of failure to excrete water load? L13
Dilutional hyponatraemia
Oedema
Hypertension
61
Treatment for fluid overload? L13
Diuretics
Salt and fluid restriction
(Dialysis + transplant)
62
What effect does CKD have on sodium levels? L13
Hypernatraemia
63
What effect does CKD have on potassium levels? L13
Hyperkalaemia when eGFR <10ml/min
64
Treatment for hypernatraemia and hyperkalaemia? L13
Salt and K+ restriction
| Dialysis + transplant
65
Treatment to prevent bone disease as a result of CKD? L13
1alpha-hydroxylated vit D replacement
Phosphate binders
Parathyroidectomy
66
Treatment for anaemia as a result of CKD? L13
Recombinant EPO
67
Treatment for high BP in CKD? L13
RAS blockage
ACE inhibitors
Diuretics
68
What is a risk from failure to excrete insulin? L13
Hypoglycaemia
69
What is a risk from failure to excrete antibiotics? L13
Encephalopathy
70
What is a risk from failure to excrete digoxin? L13
Cardiac arrhythmias
71
Signs of renal failure? (many of them) (L14 Renal failure)
```
Volume overload
Hypertension
Hypoalbuminaemia
Oedema
Hyponatraemia
Hyperkalaemia
Metabolic acidosis
Decreased renal clearance of drugs
Hyperphosphataemia
Hypocalcaemia (potentially hypercalcaemia)
Anaemia
```
72
Why do you get volume overload in renal failure? L14
GFR falls, so water and salt accumulate
73
Treatment for volume overload? L14
Furosemide
ACE inhibitors
AT1 blocker
74
Why do you get hypertension in renal failure? L14
RAA system activation
| Volume expansion
75
Why do you get hypoalbuminaemia in renal failure? L14
Leaky glomerulus means albumin and other proteins can be lost in the urine
76
Why do you get oedema in renal failure? L14
Fall in circulating oncotic pressure, means more fluid leaves vessels to go into the interstitial space, causing oedema
77
Why do you get hyponatraemia in renal failure? L14
A decrease in effective circulating volume means ADH is released, but this does not retain Na+ so sodium is lost in the urine. Osmolality is sacrificed to maintain volume
78
Why do you get hyperkalaemia in renal failure? L14
Drop in GFR means a decrease in K+ clearance. Initially this is regulated by aldosterone, but as kidney function declines, this is no longer sufficient
79
Treatment for hyperkalaemia? L14
Acute: insulin or glucose
Chronic: diuretics, potassium restricted diet
80
Treatment for hyponatraemia? L14
V2 receptor antagonists
81
Why do you get metabolic acidosis in renal failure? L14
Loss of ability to secrete H+ and produce new HCO3- leads to H+ ion increase and decrease in pH
82
Examples of drugs that have side effects from decreased renal clearance? L14
Opiates
Metformin
Digoxin
Furosemide
83
Why do you get hyperphosphataemia in renal failure? L14
Decreased GFR means decreased phosphate clearance
84
Why do you get hypocalcaemia in renal failure? L14
Decrease in active vit.D leads to increase in PTH, so more calcium is resorbed from bone, can lead to osteomalacia and hyperparathyroidism
85
Why do you get anaemia in renal failure? L14
Decreased EPO
86
Signs of uraemia? L14
```
Uraemic frost on skin
Encephalopathy
Seizures
Pruritis
Nausea
Sexual dysfunction
```
87
Who is at risk for acute kidney injury? (L15 Acute renal injury)
```
Elderly
DM pts
Hypertensive pts
Heart disease pts
CKD pts
```
88
Pre-renal causes of acute kidney injury? L15
Hypotension
Hypovalaemia
Renal artery occlusion
89
Treatment for pre-renal cause of acute kidney injury? L15
Treat underlying cause
| Fluid volume replacement
90
Post-renal causes of acute kidney injury? L15
Obstruction of urinary system e.g. tumour, stones, fibrosis, benign prostate
91
Renal causes of acute kidney injury? L15
Intrinsic disease of kidney or systemic disease affecting kidney
92
Treatment of inflammatory renal disease? L15
Steroids
| Cyclophosphamide
93
Causes of death from AKI? L15
```
Underlying disease
Infection
Hyperkalaemia
Acidosis
Pulmonary oedema
```
94
What separates a patient's blood and dialysis fluid during dialysis? L16
Semi-permeable membrane
95
Two types of dialysis? L16
Peritoneal
| Haemolysis
96
Possible complications from dialysis? L16
```
Infection
Does not last for every pt
LVH due to hypertension and fluid overload
Anaemia
Bone disease
```
97
Where is a transplanted kidney often placed? L16
In iliac fossa, retroperitoneal
98
Where do transplanted kidneys come from? L16
Cadaveric donors- BSD or CDD
| Living donors- must be assessed more carefully
99
What do you screen potential donors for when wanting to transplant a kidney? L16
Human Leukocyte Antigen (HLA)- screen patients for anti-HLA antibodies
100
What happens in cell-mediated rejection of an organ transplant? L16
Cellular debris goes to secondary lymphoid tissues --> presented on APC to T cell --> releases IL-2 which continues the T cell cycle --> cytokines released --> macrophages and B cells activated
101
What does every pt need to take if they have received a donor organ? L16
Immunosuppressants
102
Give examples of immunosuppressants and how they work. L16
Steroids prevent IL-2 release
Basiliximab block IL-2 receptors
Ciclosporin inhibits calcineurin
103
Side of effects of steroids? L16
Weight gain
Thin skin
Hypertension
Osteoporosis
104
Side effects of ciclosporin? L16
Infection
| Nephrotoxic
105
Define shock. L17
Inadequate perfusion of vital organs
106
Two types of shock? L17
Distributive/ high-output
| Non-distributive/ low-output
107
What happens in cardiogenic shock? L17
```
Due to any 'pump' failure, commonly MI
Decreased ABP and ECV
INCREASED CVP
Reflex widespread vasoconstriction
Increased symp activity to kidney, lowering GFR, activating RAA system
```
108
What happens in hypovolaemia? L17
Due to haemorrhage, burns, vomiting, diarrhoea, dehydration
Decreased ABP and ECV
DECREASED CVP
Increased symp activity to kidney, lowering GFR, activating RAA system
109
Effects of haemorrhage on tissues? L17
Anaerobic respiration leads to lactic acidosis
Tissue damage causes K+ release
Cardiac hypoxia further decreases CO
Renal hypoxia leads to AKI
110
What is the adaptive renal response to shock? L17
Decreased venous pressure leads to ADH release which leads to water retention and hyponatraemia. This stimulates aldosterone release and so then the RAA system then retains both sodium and water.
111
What cell type is EPO synthesised from? L18
Peritubular fibroblasts
112
Stimulus for EPO production? L18
Hypoxia (HIF-2)
| Low iron
113
How is vit.D metabolised? L18
vit.D --> 25-vit.D in the liver
| 25-vit.D --> 1,25-vit.D in the kidney
114
Four layers of bladder wall from the innermost layer? L19
Urothelium
Lamina propria
Detrusor smooth muscle
Serosa
115
What is the function of the type of junction between urothelium cells? L19
Tight junctions; decrease permeability
116
Parasympathetic transmitter and receptor on detrusor muscle? L19
Ach on M3 receptors, cause contraction
117
Sympathetic transmitter and receptor on detrusor muscle? L19
Noradrenaline on beta-3 receptors, causing relaxation
118
Which nervous systems are active/inactive in continence? L19
Somatic ACTIVE
Symp ACTIVE
Parasymp INACTIVE
= sphincters contracted
119
Which nervous systems are active/inactive in voiding? L19
Somatic INACTIVE
Symp INACTIVE
Parasymp ACTIVE
= sphincters relax, walls contract
120
Treatment for overactive bladder? L19
Anti-muscarinics
Botulinum toxin
Beta-3 agonists
121
Treatment for urinary outflow obstruction? L19
TURP
Alpha-receptor antagonists
5alpha-reductase inhibitors
122
Four effects of aldosterone? L11
Increase activity of basolateral Na+/K+ pumps in DT and CD
Upregulates ENaCs
Increases K+ secretion
Increases H+ secretion in the intercalated cells of the CCDs
123
What are the levels of ADH in central diabetes insipidus? L10
Low due to decreased production from the hypothalamus
124
What are the levels of ADH in nephrogenic diabetes insipidus? L10
High due to no response of ADH in the kidneys
