Urinary Flashcards
(111 cards)
1
Q
Factors determining GFR
A
Glomerular capillary hydrostatic pressure
Tubular hydrostatic pressure
Average glomerular oncotic gradient
Ultrafiltration coefficient
2
Q
Podocyte morphology
A
“Foot” processes
Attach to basal lamina
3
Q
Podocyte function
A
Form slit pores
Contract
Stabilise structure
4
Q
Endothelial cell morphology
A
Fenestrated
Surface glycocalyx
5
Q
Endothelial cell function
A
Forms fenestrations
6
Q
Mesangial cell morphology
A
Wrap around capillaries
Contractile
Form mesangial matrix
7
Q
Mesangial cell function
A
Phagocytic
“Clean the filter”
8
Q
Measures of GFR
A
Inulin urinary clearance
Plasma clearance of suitable substance eg iohexol
9
Q
Filtration fraction
A
Fraction of the plasma passing through the glomerulus that appears in the filtrate
GPR/RPF
10
Q
Mechanisms of GFR autoregulation
A
Myogenic tone
- Afferent arteriole restricts in response to stretch
Tubuloglomerular feedback
-Cl- detected by macula densa
-If high, afferent constricts and efferent relaxes
-If low, efferent constricts and afferent relaxes
11
Q
Macula densa mediators of GFR regulation
A
Adenosine
Nitric oxide
12
Q
Adenosine role in GFR regulation
A
Release stimulated by high Cl-
Constricts afferent arteriole
Inhibits renin secretion
13
Q
NO role in GFR regulation
A
Release stimulated by low Cl-
Relaxes afferent arteriole
Stimulates renin secretion
14
Q
Prostaglandin effect on GFR
A
Increases renin release
Protective against excessive constriction of afferent arteriole if BP drops
15
Q
Renin-angiotensin system summary
A
Renin cleaves angiotensinogen to make angiotensin I
Angiotensin Converting Enzyme cleaves angiotensin I to make angiotensin II
16
Q
Role of angiotensin II
A
Constricts efferent arteriole
Enhances sodium and water absorption in proximal convoluted tubule
17
Q
Proximal Convoluted Tubule characteristics
A
Returns 65-75% of filtrate to plasma
Reabsorbtion is fairly non-selective
Proximal tubular cells make calcitriol
18
Q
Proximal convoluted tubule epithelial structure
A
Brush border
Microvilli
Invaginations of the basolateral plasma membrane
Tight junctions between cells
Full of mitochondria and endocytic vesicles
19
Q
PCT co-transporter characteristics
A
Move sodium ions out of tubule down electrochemical gradient, co-transporting amino acids, glucose etc along with them
Can become saturated (leading to glucosuria in DM patients)
20
Q
Bicarbonate reabsorption in PCT
A
Almost all filtered out bicarbonate is reclaimed in the PCT
Uses CARBONIC ANHYDRASE (intracellular and in brush border)
Dissociates, then is absorbed as carbonic acid
21
Q
Characteristics of peri-tubular capillaries
A
Low hydrostatic pressure
High colloid osmotic pressure
Favours water resorption into capillaries
22
Q
Substances reabsorbed in PCT
A
Water
Bicarbonate ions
Chloride ions
Peptides and proteins
23
Q
Cl- movement in PCT
A
Move through tight junctions between tubular epithelial cells
Sodium ion transport out of tubule creates electrochemical gradient to allow chloride ions to move
24
Q
Water movement in PCT
A
Transport of solutes out of lumen creates osmotic gradient to allow water to leave
Peritubular capillaries pick up reabsorbed water and solutes
25
Peptide and protein movement in PCT
Taken up by pinocytosis
Digested and returned to blood as amino acids
26
Transport system in thick ascending limb
Active transport of sodium, potassium and calcium out of lumen
Na/K/Cl co-transporter
Energy provided by Na/K ATPase
Most K recycled back into lumen
Water doesn't follow (impermeable to water)
(20-30% filtered sodium and chloride reabsorbed here)
27
Trends in fluid osmolarity along nephron tubule
Highest at bottom of loop of Henle and end of collecting duct
28
Role of connecting tubule and collecting duct
Sensitive to ADH
Further concentration of urine controlled by action of ADH on collecting tubule/duct permeability to water
29
Counter-current multiplier system role
Convert small horizontal osmolarity gradient into larger vertical gradient across loop of Henle
Allows variation in urine volume
30
ADH characteristics
Peptide hormone
Released from posterior pituitary
Hypothalamic osmoreceptors sense osmolarity of CSF and ECF, stimulate posterior pituitary to release ADH
31
ADH actions
Acts on V2 receptors on basolateral membranes of cortical connecting tubule and collecting duct
GPCRs activate adenylate cyclase and increases cAMP
Causes aquaporin insertion into apical membrane
32
Controllers of phosphate transport in PCT
PTH
FGF-23
33
Movement in PCT
All glucose, amino acid and bicarbonate reabsorbed
Peptides and small proteins reabsorbed
Sodium and chloride ion concentration stays the same
Some organic acids secreted in filtrate
Urea/waste products NOT reabsorbed
34
Transport system in descending limb
Highly permeable to water
Water passively diffuses out
35
Function of distal tubule
Finer control of urine composition
Hormone-mediated control of sodium reabsorption (for blood pressure and ECF volume control), potassium excretion (linked to control of sodium concentration in ECF), acid excretion, carbonic acid regeneration, calcium + magnesium excretion (linked to phosphate regulation)
36
Regulation of distal tubule filtration
Tubuloglomerular feedback
Macula densa senses Cl-
Responds to high Cl- by constricting afferent arteriole and relaxing efferent arteriole
Responds to low Cl- by relaxing afferent arteriole and constricting efferent arteriole
37
Early distal tubule
Further dilution of tubular fluid
Impermeable to water
Sodium and chloride reabsorption by co-transport
Calcium and magnesium also "handled"
38
Late distal tubule
Acid base balance
Can make ammonia to excrete more acid
PTH regulates calcium
Sodium reabsorption and potassium excretion regulated by aldosterone
39
Acid base buffering
Bicarbonate/CO2 is the most important blood buffering system
Blood pH = 6.1 + log[HCO3-]/pCO2
pCO2 is in equilibrium with [HCO3-]
Kidneys keep [HCO3-] at 24mmol/l
40
Bicarbonate regeneration in the distal tubule
CO2 enters cell via serosal surface, combines with water to make carbonic acid which dissociates into hydrogen ions and bicarbonate ions. Bicarbonate ions exit from serosal surface while hydrogen ion are excreted into filtrate.
41
Processing of excess acid
Sodium bicarbonate combines with acid to make water, CO2 and a sodium salt of the acid.
CO2 is rapidly excreted from lungs
Kidney can excrete ammonia
Urine can be quite acidic
42
Sodium homeostasis determination of ECF volume
ECF volume determined by [NaCl] in ECF
43
Sodium homeostasis and ECF volume impact on blood pressure
BP lowered by sodium conservation in kidney
BP raised by sodium excretion in kidney
44
Aldosterone
Corticosteroid hormone
Secreted from zona glomerulosa of adrenal cortex
Stimulates angiotensin II secretion
Inhibits atrial natriuretic peptide secretion
45
Sodium conservation
Inhibition of natriuretic system
Sympathetic nervous system constricts renal arterioles, increases tubular resorption of salt and water, and stimulates renin secretion
Activation of RAAS maintains GFR at lower perfusion pressure, increases sodium resorption in PCT and stimulates aldosterone secretion
46
Sodium excretion
Macula densa senses more NaCl
Adenosine switches off renin production, causing aldosterone levels to fall
Atrial stretch triggers secretion of atrial natriuretic peptide
Endogenous digitalis-like factor may have a role but we know little about it
47
Natriuretic system
Heart produces ANP in response to high blood pressure
48
Renal handling of phosphate
Actively transported in PCT by sodium cotransport, regulated by PTH
Overflow process is used when filtered phosphate exceeds its transport maximum
49
Factors determining rate of phosphate excretion
Plasma phosphate concentration
GFR
Enhanced by PTH and FGF-23
50
Phosphate transport in the PCT
Sodium cotransporters move phosphate ions out of tubular lumen
51
PTH effect on phosphate excretion
Increases
52
Response to low blood ionised calcium
Increased PTH secretion, promoting bone resorption, calcium reabsorption and potassium excretion and synthesis of calcitriol
53
Renal handling of calcium
Both free and complexed calcium are filtered
65% is passively reabsorbed in PCT
25-30% reabsorbed in loop of Henle
5-9% reabsorbed in DCT/CCT
Calcitonin INHIBITS calcium reabsorption
54
Importance of pH homeostasis
Protein conformation and enzyme activity altered by pH changes
55
Normal ECF pH
7.4 (ICF is slightly more acidic)
56
Mechanism of action of aldosterone
Increases number of sodium and potassium channels in apical membrane of late distal tubule
Increases number of Na/K pumps in basolateral membranes
57
Osmotic diuretic site of action
Loop of Henle
58
Osmotic diuretic mechanism
Expand ECF, inhibit renin release, decrease blood viscosity, increases removal of NaCl and urea, increases renal blood flow
59
Loop diuretic site of action
Thick ascending limb of loop of Henle
60
Loop diuretic mechanism
Inhibits Na/K/Cl co-transporter
61
Carbonic anhydrase site of action
PCT, DCT
62
Carbonic anhydrase mechanism
Catalyses carbonic acid dissociation, bicarbonate regeneration etc
63
Thiazide site of action
DCT
64
Thiazide mechanism
Inhibits Na and Cl transport
Decreases calcium excretion
65
Aldosterone antagonist site of action
DCT
66
Aldosterone antagonist mechanism
Antagonises ANP inhibition and angiotensin II secretion
67
Clinical indication for osmotic diuretic
Acute glaucoma
Acute kidney injury
Cerebral oedema
Contra-indicated for intracranial haemmorhage
68
Clinical indication for loop diuretic
Acute and chronic heart failure
69
Clinical indication for carbonic anhydrase
Topical treatment of glaucoma
Weak and many side effects (metabolic acidosis)
70
Clinical indication for thiazide
In veterinary, can be used to prevent calcium oxalate uroliths and as an additive therapy for refractory heart failure
RISK OF HYPOVOLAEMIA in veterinary patients
Mainly used in humans
Pulmonary oedema
Oedema caused by heart failure and cirrhosis
71
Clinical indication for aldosterone antagonist
Ascites secondary to heart failure and liver cirrhosis
72
Sodium channel inhibitor site of action
LDCT and collecting duct
73
Sodium channel inhibitor mechanism
Increases sodium excretion, decreases H+ and potassium excretion
74
Sodium channel inhibitor clinical indication
Unusual in veterinary
Sometimes used as a secondary diuretic in refractory oedema
Used in humans combined with thiazide and loop diuretics
Weak diuretic
Contraindicated in hyperkalaemia
75
Importance of [H+] in normal physiological function
Very reactive
Binds proteins/enzymes,
76
Acid
A substance that can donate protons
77
Base
A substance that can accept protons
78
pH
-log[H+]
79
pKa
Measure of the strength of an individual acid ie how likely it is to dissociate
pKa = -log[Ka] so smaller pKa means stronger
80
Buffer solution
Minimises pH changes by taking up or donating H+
Partially dissociates in solution to form a weak acid and its conjugate base
Can't actually remove things, that is for lungs and kidneys
81
Henderson-Hasselbach equation
pH = pKa + log([base]/[acid])
therefore for bicarbonate system it is:
pH = 6.1 + log([HCO3-]/[0.03xCO2])
82
Role of CO2 in blood buffering
Removed from lungs
83
Role of haemoglobin in blood buffering
80% of non-bicarbonate buffering
H+ ions react with oxygenated haemoglobin, causing it to release its oxygen and take up the H+
84
Major blood buffering systems
Bicarbonate/carbonic system
Haemoglobin buffer
Phosphate buffer
85
Role of compensation in the maintenance of normal acid base balance
Renal and respiratory systems used to add or remove acid and base
86
Normal blood pH
7.35-7.45
87
Body systems involved in acid base balance
Respiratory
Renal
Hepatic
88
Base excess
Amount of acid that must be added to oxygenated blood to restore pH to 7.4 at 37'C and pCO2 of 40mmHg
89
Anion gap
([Na+]+[K+])-([Cl-]+[HCO3-])
"Normal" value is 15-25
90
Changes occurring with acute acid base balance disturbances
Respiratory compensation
91
Changes occurring with chronic acid base disturbances
Renal compensation (using bicarbonate, phosphate and ammonia)
Ammonia excretion especially important
92
Base deficit
Amount of acid that must be added to oxygenated blood to restore pH to 7.4 at 37'C and pCO2 of 40mmHg
93
Causes of metabolic acidosis
Loss of bicarbonate from:
Failure of reabsorption in kidney
Diarrhoea
Gain of acid from:
Increased lactate
Diabetic ketoacidosis
Uraemic acids
Toxins (methanol. salicylic acid, ethylene glycol)
94
Causes of metabolic alkylosis
Loss of acid from:
H+ loss to vomiting
Increased acid loss from kidney (eg loop diuretic loss)
Increased base
Sodium bicarbonate administered
95
Respiratory acidosis
High blood CO2
96
Respiratory alkalosis
Low blood CO2
97
Metabolic acidosis
Low HCO3 or base deficit
98
Metabolic alkalosis
High HCO3 or base excess
99
Approach to acid base analysis
1. Is pH normal?
2. Check CO2 for respiratory component
3. Check BE or HCO3 for metabolic component
4. Whichever process is pointing in same direction as pH is the primary one
5. Is there compensation?
6. If primary metabolic acidosis, check anion gap
100
Causes of respiratory acidosis
Airway obstruction
Depression of respiratory centres by anaesthetic drugs
Neurological disease of brainstem and cervical spinal cord
Neuromuscular disease
Prevention of lung expansion (eg pleural effusion)
101
Causes of respiratory alkalosis
Fear/anxiety
Fear
Pain
Corticosteroids
Hypoxaemia
Brain injury
102
Signs of mixed disorders of acid base balance
Both metabolic and respiratory systems affected with normal pH
Inadequate or excessive compensation
103
Why do we measure urinary protein:creatinine ratio?
How much of the protein is being lost due to kidney damage
>0.5 is proteinuric
104
Role of RAAS in regulating intraglomerular pressure
Angiotensin II preferentially constricts efferent arteriole, so inhibiting its production from renin reduces blood pressure in the kidney, reducing damage to the glomerular filter
105
Acidaemia
Blood pH < 7.35
106
Alkalaemia
Blood pH >7.45
107
Location of peripheral chemoreceptors
Carotid bodies
Aortic bodies
108
Respiratory response to decrease in blood pH
Increase in [H+] detected by chemoreceptors
Message sent to respiratory centres in brainstem
Causes hyperventilation in order to lower pCO2, increasing pH back towards normal
109
Respiratory response to increase in blood pH
Decrease in [H+] detected by chemoreceptors
Message sent to respiratory centres in brainstem
Causes hypoventilation in order to decrease pCO2, decreasing pH back towards normal
110
Three methods of acid-base regulation by the kidney
1. Reabsorbs nearly all filtered bicarbonate
2. Excretes acid in the urine
3. Regenerates bicarbonate lost to buffering via excretion of ammonium salts and phosphate salts
111
