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Principles of Physiology and Pharmacology > Kidney Function > Flashcards

Kidney Function Flashcards

Understand the nature of the glomerular filter and the dynamics of ultrafiltration Define clearance and its use in the study of renal physiology Explain how glomerular filtration rate and effective renal plasma flow are measured Describe the processes of tubular reabsorption of glucose, amino acids etc. Describe the processes of tubular secretion of organic acids and bases

1
Q

What are the functions of kidneys?

A

Metabolite excretion (and ingested substances)
Processes the plasma
Control of body fluid composition

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2
Q

How are the functions of the kidneys achieved?

A

Volume Regulation (linked to Na+ conc)
Osmoregulation
pH regulation

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3
Q

What are some examples of endocrine hormones that act on the kidneys?

A 
ADH
Aldosterone
Natriuretic Peptides
Parathyroid hormone
FGF23
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4
Q

What are some examples of endocrine hormones produced by the kidneys?

A 
Renin
Vitamin D
Erythropoietin
Prostaglandins
alpha Klotho
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5
Q

Which kidney is slightly lower than the other?

A

The right kidney is lower than the left kidney

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6
Q

What is the outer region of the kidney called?

A

Cortex

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7
Q

What is the inner region of the kidney called?

A

Medulla

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8
Q

What is the basic unit of the kidney?

A

Nephron

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9
Q

What do nephrons consist of?

A

A renal corpuscle and a thin hollow tube

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10
Q

What is a renal corpuscle?

A

The initial filtering component of the nephron

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11
Q

What structures make up the renal corpuscle?

A

Bowman’s capsule

Glomerulus

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12
Q

What is the Bowman’s capsule composed of?

A

Fenestrated Endothelial cells

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13
Q

What is the Glomerulus composed of?

A

Compact interconnected capillary loops

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14
Q

What is the blood supply of the Glomerulus?

A

Blood supply from the afferent arteriole

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15
Q

Through which arteriole does the blood leave the glomerulus?

A

The efferent arteriole

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16
Q

What do the fenestrated capillary endothelium rest on?

A

A protein basement membrane

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17
Q

The basement membrane has negative charges. Why is that?

A

Has fixed polyanions

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18
Q

What is a feature of the tubular epithelium

A

Specialised filtration slits for fluid (at the level of the filtration interface)

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19
Q

What are podocytes?

A

Specialised epithelial cells with a central cell body and a long foot process which extends from it

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20
Q

What links the foot processes together?

A

Filtration slit proteins

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21
Q

What are the names of filtration slit proteins?

A

Nephrin

Podocin

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22
Q

What are the 2 types of nephrons?

A

Cortical

Juxtamedullary

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23
Q

Where is the renal corpuscle found in cortical nephrons?

A

Found in the outer 2/3rds of the cortex

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24
Q

Where is the renal corpuscle found in juxtamedullary nephrons?

A

Found in the inner 1/3rds of the cortex

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25
Q

What are the 2 types of cells that make up the juxtamedullary apparatus?

A

Juxtaglomerular cells

Macula Densa cells (directly opposite the juxtaglomerular cells)

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26
Q

What do juxtaglomerular cells do?

A

Secrete renin into the blood of the afferent arteriole

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27
Q

Where are Macula densa cells found?

A

In the walls of the ascending limb of the loop of Henle

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28
Q

What passes in between the afferent and efferent arteriole?

A

The ascending limb of the loop of Henle

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29
Q

Where are mesangial cells located?

A

Around the capillaries

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30
Q

Do the mesangial cells contribute to the filtration interface (barrier)?

A

No

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31
Q

Mesengial cells have smooth muscle. What can they do?

A

Contract meaning they can control the SA of the filtration interface

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32
Q

What are the 2 sets of arterioles in series which go to the nephrons?

A

Afferent

Efferent

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33
Q

What are the 2 capillary beds that are in series?

A

Glomeruli

Peritubular

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34
Q

Where is the glomeruli capillary bed located?

A

In the renal corpuscle

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35
Q

Where do Peritubular capillaries arise from?

A

The afferent arteriole

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36
Q

Peritubular capillaries in the region of the loop of Henle are called…

A

Vasa Recta

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37
Q

What are the 4 basic renal processes?

A

Glomerular Filtration
Tubular Secretion
Tubular Reabsorption
Metabolism

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38
Q

Where does glomerular filtration take place?

A

Only in the renal corpuscle

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39
Q

What is glomerular filtration?

A

The movement of fluid and solutes from the glomerular capillaries into Bowman’s space

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40
Q

What type of process is the glomerular filtration?

A

Non-selective process

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41
Q

What is an ultrafiltrate?

A

The fluid in the Bowman’s space

Beginning of the formation of urine

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42
Q

What is Tubular Secretion?

A

The secretion of solutes from the lumen of the peritubular capillaries into the lumen of the tubules

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43
Q

What is Tubular Reabsorption?

A

The movement of materials from the filtrate in the tubules into the peritubular capillaries

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44
Q

What does it mean by metabolism?

A

The kidney is able to eliminate certain types of molecules

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45
Q

The amount excreted in urine is…

A

The amount filtered + the amount secreted - the amount reabsorped

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46
Q

What is an example of a substance that is filtered and secreted but not reabsorbed?

A

PAH- para-aminohippuric acid

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47
Q

What is an example of a substance that is filtered and some of it is reabsorbed?

A

Water and most electrolytes

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48
Q

What is an example of a substance that is filtered and completely reabsorbed?

A

Glucose and Bicarbonate

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49
Q

What determines what gets through the glomerular filtration barrier?

A

Molecular size, shape and charge

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50
Q

What is the molecular size cut-off for the filtration interface?

A

7000kDa

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51
Q

The basement membrane is negative, what type of ion is more likely cross the membrane?

A

Positively charged

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52
Q

What can infection, damage to glomerulus or very high blood pressure result in?

A

Protein in the urine
Haemoglobin in urine
Red cells in urine

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53
Q

What is the glomerular filtration rate?

A

The volume of fluid filtered from the glomeruli per minute (ml/min)

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54
Q

What does the GFR depend on?

A

Starling Forces
Surface are of filtration interface
Hydraulic permeability of capillaries

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55
Q

What is the GFR regulated by?

A

Neural and hormonal input

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56
Q

How can hydrostatic pressure be altered?

A

Constricting or dilating the arterioles

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57
Q

What are Starling forces?

A

The opposing hydrostatic and oncotic (colloid osmotic) pressures

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58
Q

What direction does the driving force of fluid movement in filtration go in?

A

From capillary lumen to capiscular space

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59
Q

Which nervous system alters the surface area of the filtration interface?

A

Sympathetic nervous system

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60
Q

What is the definition of clearance?

A

The volume of plasma that is cleared of a substance per unit time

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61
Q

What is the equation of renal clearance?

A

(Concentration in urine* Volume of Urine)/Concentration in plasma

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62
Q

What are the units for renal clearance?

A

The same units for the volume of urine

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63
Q

Why can the clearance of inulin measure GFR?

A

Inulin is freely filtered, but not reabsorbed/secreted/metabolised
Used experimentally

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64
Q

What is used clinically for estimate GFR?

A

Creatinine (slightly secreted)

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65
Q

What is different about the equation used in the clinic to determine clearance?

A

Includes variables: age and weight

Units and value will differ

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66
Q

What is the definition of the haematocrit?

A

Percentage of whole blood that is made up of cells

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67
Q

What is the approximate renal plasma flow?

A

600ml/min

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68
Q

What is the formula for blood flow?

A

(Plasma Flow)/(1-haematocrit)

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69
Q

Where is the main region where reabsorption takes place?

A

Proximal Tubule: proximal convoluted tubule and the proximal straight tube

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70
Q

What cells make up the wall of the proximal tubule?

A

Single layer of columnar cells

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71
Q

What transporters are present for proximal reabsorption of organic nutrients?

A

Na+-coupled co-transporter
A tubular maximum (Tm) system
Specific Transporters

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72
Q

Where are Na+-coupled co-transporters expressed?

A

Luminal membrane of the tubule epithelial cells

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73
Q

Why can the Na+-coupled co-transporter undergo saturation?

A

Has a transfer maximum (tubular maximum)

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74
Q

What is a tubular maximum (transfer maximum)?

A

A transporter only has a limited number of binding sites for the molecule. Once they are full, they cannot transport anyway

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75
Q

What are some examples of organic nutrients?

A

Glucose

Amino acids

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76
Q

Why is glucose not normally present in the urine?

A

Filtered glucose is normally reabsorbed and does not undergo secretion

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77
Q

Where is the Na+-K+-ATPase pump expressed?

A

The basolateral membrane

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78
Q

What does the Na+-K+-ATPase pump do?

A

Maintains a low sodium concentration inside the cell compared to the outside of the cell

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79
Q

Where are amino acid reabsorbed?

A

Proximal tubule

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80
Q

How are filtered proteins reabsorbed?

A

Endocytosis in the PCT

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81
Q

What happens to reabsorbed filtered proteins?

A

Degraded to amino acids

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82
Q

What is passively reabsorbed by the PCT?

A

Urea
Chloride
Potassium
Calcium

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83
Q

What is secreted in the proximal tubule?

A

Endogenous molecules
Drugs
Diagnostic agent

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84
Q

What are some examples or endogenous molecules?

A 
Bile salts
Fatty acids
Prostaglandins
Creatinine
Dopamine
Choline
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85
Q

What are some examples of drugs?

A 
Furosemide
Penicillin
Acetozolamide
Cimetidine
Morphine
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86
Q

What is an example of a diagnostic agent?

A

Para-aminohippuric acid (PAH)

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87
Q

How are organic anions secreted in Proximal Distribution?

A

Organic anion (OA-) enters cell in exchange for dicarboxylate (DC-) (organic anion transporters (OAT1 or OAT3)).
DC- accumulate in cells by metabolism and Na+-coupled cotransport
OA- enters tubule lumen via ATP- dependent transporters

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88
Q

How are organic cations secreted in Proximal Convoluted Tubule?

A

Enter vell via facilitated organic cation transporters (OCT2)
Enter tubule via multidrug and toxin extrusion proteins (MATEs) antiporter in exchange for H+ and/or OCTN

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89
Q

What is osmolality?

A

A measure of water concentration (mosm/kg)

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90
Q

The higher the solution osmolality the…

A

Lower the water concentration

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91
Q

Why do physiologists prefer osmolality over osmolarity?

A

Osmolality is independent of the temperature whereas the osmolarity is dependent on it.

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92
Q

What is the main osmotically active solute in plasma?

A

Sodium

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93
Q

What is the plasma sodium concentration?

A

135-145mmol/l

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94
Q

Sodium is free filtered at the renal corpuscle. What is the equation to find out what is filtered?

A

Plasma Na+ concentration (mmol/l) * GFR (l/min)

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95
Q

What kind of process is sodium reabsorption?

A

Active

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96
Q

Where does sodium reabsorption take place?

A

Proximal tubule
Thick ascending limb
Distal tubule
Collecting duct

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97
Q

What are the types of cells in the collecting duct?

A

Intercalated cell

Principal cell- sodium reabsorption takes place

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98
Q

Where does majority of sodium reabsorption take place?

A

Proximal tubule

Thick ascending limb

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99
Q

What parts of the Nephron are under hormonal control?

A

Distal tubule

Principle cells of the collecting duct

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100
Q

Is there sodium reabsorption in the descending limb?

A

No

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101
Q

What type of sodium reabsorption occurs in the thin ascending loop?

A

Passive- movement of Na+ from an area of high conc to an area of low conc with no transport mechanism or energy

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102
Q

Where is the filtrate?

A

In the lumen

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103
Q

What Na transport pathways are present in the proximal tubule?

A

Na+ nutrient symporter
Na+: H+ Exchanger- NH3
Na+:K+ ATPase pump
Na+ HCO3- transporter

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104
Q

Where is the sodium potassium ATPase pump expressed in the proximal tubule?

A

Basolateral membrane

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105
Q

What type of transporter is the sodium potassium ATPase in the proximal tubule?

A

Primary active transporter

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106
Q

What does the sodium potassium ATPase do?

A

ATP hydrolysis for sodium to move against conc gradient out of cell and potassium into the cell

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107
Q

What is the sodium conc inside a proximal tubule cell?

A

Low

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108
Q

What is useful about Na+ moving into the cell?

A

Can provide energy for the movement of another ion/molecule/nutrient against its concentration gradient

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109
Q

What isoform of the sodium hydrogen exchanger is present on the luminal membrane of the proximal tubule cells?

A

NH3

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110
Q

Where is the sodium hydrogen exchanger expressed in proximal tubule cells?

A

Luminal membrane

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111
Q

How does Sodium enter the proximal tubule epithelium?

A

Via the sodium hydrogen exchanger and the sodium nutrient symporter

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112
Q

What happens to the sodium that is inside the proximal tubule cell?

A

Moved into the interstitial by the sodium bicarbonate transporter or by the sodium potassium ATPase pump

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113
Q

How are chloride ions reabsorbed in the proximal tubule?

A

Mainly passive diffusion between cells which is dependent on Na to maintain electro-neutrality

114
Q

What sodium transport pathways are present in the thick ascending limb?

A

Na+:K+:2Cl- cotransporter

Na+:K+ ATPase pump

115
Q

What other channels are present on the cells in the thick ascending limb?

A

K+ channel (luminal membrane)
K+ Cl- symporter (basolateral membrane)
Cl- channel (basolateral membrane)

116
Q

Where is the Na+:K+:2Cl- cotransporter located in the thick ascending limb?

A

Luminal membrane

117
Q

What does the Na+:K+:2Cl- cotransporter do?

A

Moves sodium into the cell while moving potassium ions against their conc gradient into the cell

118
Q

What happens to the sodium ions inside the thick ascending limb cells?

A

They pass into the interstitial fluid surrounding the capillaries by the Na+:K+ ATPase pump

119
Q

What happens to the potassium ions inside the thick ascending limb cells

A

Return to the filtrate by moving down their conc gradient through potassium channels

120
Q

What does the potassium ions cause the filtrate to do?

A

Causes the filtrate to have a positive charge
This will repel other positively charged molecules such as sodium.
This means sodium will move between the cells

121
Q

What sodium transport pathways are present in the distal tubule?

A

Na+:Cl- cotransporter

Na+:K+ ATPase pump

122
Q

Where is the Na+:K+ ATPase pump located in the distal tubule cells?

A

Basolateral membrane

123
Q

Where is the Na+:Cl- cotransporter located in the distal tubule cells?

A

Luminal membrane

124
Q

What direction does the sodium travel in through the Na+:Cl- cotransporter on the distal tube?

A

From the filtrate into the cell

125
Q

What happens to the sodium ions that are in the distal tubule cells that have entered through the Na+:Cl- cotransporter?

A

They are moved into the interstitial fluid by the Na+:K+ ATPase pump

126
Q

What sodium transport pathways are present in the principle cells of the collecting duct?

A

Na+ channels

Na+:K+ ATPase pump

127
Q

Where is the Na+:K+ ATPase pump located in principle cells of the collecting duct?

A

Basolateral membrane

128
Q

Where is the Na+:Cl- cotransporter located in principle cells of the collecting duct?

A

Luminal membrane

129
Q

How does the sodium enter the principle cells of the collecting duct?

A

Through the luminal membrane

130
Q

What does water reabsorption depend on?

A

Osmosis
Sodium reabsorption
Tubule Permeability

131
Q

What is osmosis?

A

Movement of water from high concentration through a partially permeable membrane to an area of low concentration

132
Q

What do all basolateral membranes of renal cells have?

A

Aquaporins

133
Q

What are aquaporins?

A

Water channels

134
Q

Are aquaporins always present on the luminal membrane of renal tubule epithelial cells?

A

No- there is variable expression of water channels, therefore varied water permeability properties

135
Q

How do sodium ions move from the tubular lumen into the interstitial fluid?

A

Down its conc gradient into the tubular epithelial cells and then into the interstitial fluid by the sodium potassium ATPase pump

136
Q

What happens to the osmolality of the tubule when the sodium leaves?

A

The osmolality decreases

137
Q

What happens to the osmolality of the interstitial fluid when the sodium enters?

A

The osmolality increases

138
Q

What water channels are present in the proximal tubule which allows water to move into the interstitial fluid?

A

AQP1 - aquaporin 1 water channels

139
Q

AQP1 channels are present in the proximal tubule. Where are they found on the tubular epithelial cells?

A

The luminal membrane

140
Q

What is isotonic reabsorption?

A

Water can move between the cells because the tight junctions have high water permeability

141
Q

What happens to the water from the tubular lumen once it is in the interstitial fluid?

A

It moves by bulk flow into the peritubular capillaries

142
Q

What force is key in moving the water into the peritubular capillaries by bulk flow?

A

Hydrostatic forces

143
Q

Why is there no effect on osmolarity/osmolality even though the filtrate volume is reduced?

A

Filtrate osmolality (proximal tubule) =ultrafiltrate osmolality (Bowman’s capsule) = plasma osmolality

144
Q

What is the osmolality of concentrated urine in relation to plasma?

A

Higher than plasma

145
Q

Where does the production of concentrated urine take place?

A

Loop of Henle

146
Q

How does the kidney produce concentrated urine?

A

It separates Na+ and water reabsorption

Generates high osmolarity medullary interstitium to drive water reabsorption

147
Q

What does the loop of Henle consist of?

A

Descending and ascending limb

148
Q

What are the limbs separated by?

A

Medulla with medullary interstitium

149
Q

What is the flow in loop of Henle?

A

Countercurrent- flow in descending limb moves downwards towards the turn and flow in the ascending limb moving upwards

150
Q

What happens to the sodium at the start of the descending loop?

A

Some sodium ions passively diffuse

151
Q

Is the sodium diffusion into the descending loop classed as reabsorption?

A

No because it is movement into the lumen of the filtrate not the tissue

152
Q

What channels are present in the luminal membrane of the descending limb?

A

AQP1

153
Q

What is the purpose of the mirroring of vasa recta?

A

Supply blood without washing the gradient away

154
Q

What is the permeability of the ascending and descending limb of the vasa recta?

A

Both limbs are equally permeable to salt and water

155
Q

What is the blood flow like near the descending limb of the loop of Henle

A

Slow

156
Q

What is the effect of having slow blood flow near the descending limb of the loop of Henle?

A

Any water that leaves and enters the medullary interstitium does not significantly contribute to the to the high osmolarity

157
Q

What else contributes to the high osmolality of the interstitium?

A

Urea

158
Q

What is urea the product of?

A

Protein catabolism

159
Q

Where is the urea freely filtered?

A

Renal corpuscle

160
Q

What is the urea concentration in the filtrate?

A

Same concentration as in the plasma

161
Q

What happens to the urea in the proximal tubule?

A

Passive reabsorption- passes through the luminal and abluminal membrane and between the cells

162
Q

What recycles urea?

A

The transporters in the loop of Henle and the inner medullary duct

163
Q

On which segment of the loop of Henle are the transporters present?

A

Thin descending segment

Thin ascending segment

164
Q

Where do the transporters of the loop of Henle secrete urea?

A

Into the lumen of the tubule

165
Q

On which membrane are the transporters present in the loop of henle?

A

Present in the basolateral and luminal membrane

166
Q

Where does the inner medullary collecting duct move the urea to?

A

From the filtrate into the medulla and interstitium

167
Q

In the inner medullary collecting duct what increases urea reabsorption?

A

ADH increases urea reabsorption through UT-A3 and UT-A1

168
Q

Each nephron is separate from its neighbouring nephron apart from….

A

where they merge at the level of the collecting duct

169
Q

What happens to the majority of the urea that is filtered?

A

It is reabsorbed

170
Q

What is Tonicity?

A

Concentration of non-penetrating solutes

171
Q

What arises from the loop of Henle?

A

The distal tubule

172
Q

Can water reabsorption occur at the distal tubule?

A

No

173
Q

Why can the collecting duct concentrate urine?

A

it descends into the medullary interstitium which has a high osmolarity

174
Q

What controls the water permeability of the collecting duct?

A

ADH

175
Q

What secretes ADH?

A

Posterior pituitary gland

176
Q

Where does the ADH go once it is secreted?

A

Enters the blood of the internal carotid artery and circulated in the blood to the kidney

177
Q

Where does the ADH hormone act?

A

Acts at the level of the V2 receptor which is expressed on the basolateral membrane

178
Q

What does the V2 receptor use?

A

G protein and Cyclic AMP

179
Q

What water channels are expressed on the basolateral membrane?

A

AQP3

AQP4

180
Q

What does forming concentrated urine depend on?

A

Renal medulla interstitial fluid high osmolarity

Collecting duct

181
Q

What maintains constant plasma osmolality?

A

Urine Formation

Thirst

182
Q

What is the term given to increased urine excretion?

A

Diuresis

183
Q

What is the osmolality of concentrated urine?

A

more than 300 mosmol/l

184
Q

How can an individual survive dehydration?

A

The kidneys can generate low volume concentrated urine

185
Q

What is the concentration of waste products we are obliged to eliminate each day?

A

600 mosmol

186
Q

What is the maximum urinary concentration possible?

A

1,400 mosmol/l (extreme is usually 1,200 mosmol/l

187
Q

What is the obligatory water loss per day?

A

600 mosmol/day (waste products generated)/ 1400 mosmol/l (maximal urinary concentration)= 0.428L/day

188
Q

What is the osmolality of dilute urine?

A

less than 300 mosmol/l

189
Q

What is the term given to excessive urine output?

A

Polyuria

190
Q

What is the term given to urine output lower than the obligatory water loss?

A

Oliguria

191
Q

What is the normal urine output?

A

1-2 L/day

192
Q

What is Osmolar clearance?

A

Volume of plasma cleared of osmotically active particles per unit time or the fictive urine flow that would have resulted in a urine which was isomolar to plasma

193
Q

What is the equation for osmolar clearance?

A

Osmolar clearance= (Urine osmolarity (mosm/ml) * Urine flow rate (ml/min))/ Plasma osmolarity (mosm/ml)

194
Q

What are the units of osmolar clearance?

A

ml/min

195
Q

What is the fasting osmolar clearance?

A

2-3ml/min

196
Q

What is free water clearance used to assess?

A

Renal function- ability of the kidneys to excrete dilute or concentrated urine

197
Q

What is free water clearance?

A

The volume of blood plasma that is cleared of solute-free water per unit time

198
Q

What is the equation for free water clearance?

A

C(H2O)= Urine flow rate (ml/min)- osmolar clearance (ml/min)

199
Q

What is anti-diuresis?

A

Decreased urine formation

200
Q

Where are the osmoreceptors for ADH?

A

Organum Vasculosum Lamina Terminalis
Median Preoptic nucleus
Subfornical Organ

201
Q

Where do the osmoreceptors in the OVLT, MPN and SFO signal to?

A

The magnocellular neurosecretory cells in the paraventricular and supraoptic nuclei in the hypothalamus

202
Q

What do the magnocellular neurosecretory cells do?

A

Produce and release ADH into blood through posterior pituitary

203
Q

What is the relationship between plasma ADH concentration and plasma osmolality after 285-295mosm/kg?

A

Linear

204
Q

Why is ADH effective?

A

Has a short plasma half-life (10-20 mins)

The release is rapid

205
Q

What is ADH release sensitive to?

A

Plasma osmolality

206
Q

Where are the osmoreceptors for thirst located?

A

Prelateral optic nuclei

207
Q

When are the osmoreceptors for thirst triggered?

A

When plasma osmolarity is 295 mosm/kg

208
Q

What other factors affect ADH secretion?

A

Blood pressure
Blood volume
(Angiotensin II and natriuretic peptides)

209
Q

What effect does angiotensin II have on ADH secretion?

A

Increases

210
Q

What effect does natriuretic peptides have on ADH secretion?

A

Decreases

211
Q

What else stimulates ADH secretion?

A

Nicotine
Pain
Stress
Nausea

212
Q

What else inhibits ADH secretion?

A

Alcohol

213
Q

What is diabetes insipidus?

A

Water diabetes

A disease which results in the production of very large quantities of dilute urine (dehydrate and insatiable)

214
Q

What are the characteristics of diabetes insipidus?

A

Polyruria (2L/day)
Thirst (polydipsia)
Nocturia

215
Q

What are the types of diabetes insipidus?

A

Neurogenic (no ADH secreted)

Nephrogenic

216
Q

What causes neurogenic diabetes insipidus?

A

Congenital defect

Head injury eg: trauma or brain tumour

217
Q

What causes nephrogenic diabetes insipidus?

A

Inherited mutated V2 receptor or AQP2 channel

Acquired (infection or side effect of drug e.g. lithium)

218
Q

What is osmotic diuresis?

A

Increased urination due to the accumulation of substances in the tubules of the kidney

219
Q

What are the characteristics of osmotic diuresis?

A

Polyuria (increased urination)

Thirst (polydipsia)

220
Q

What causes the increases urination in osmotic diuresis?

A

Small molecules (glycerol, mannitol and excess glucose) in the renal tubule lumen which reduce reabsorption of water which the later portions of the nephron cannot compensate

221
Q

What do potassium ions do?

A

Maintain resting membrane potential

affects membrane potential and excitability

222
Q

What potassium channels/ pumps are present on the luminal side of the proximal tubule epithelium?

A

Potassium channel (Weak)

223
Q

What potassium channels/ pumps are present on the basolateral side of the proximal tubule epithelium?

A

Sodium potassium ATPase pump
Leaky potassium ion channel
Potassium Chloride symporter

224
Q

Over 95% of Potassium ions are reabsorbed. How much of it is reabsorbed in the proximal tubule?

A

65%

225
Q

Over 95% of Potassium ions are reabsorbed. How much of it is reabsorbed in the thick ascending tubule?

A

30%

226
Q

Over 95% of Potassium ions are reabsorbed. How much of it is reabsorbed in the distal tubule?

A

5%

227
Q

What cotransporter is present on the luminal side of the thick ascending limb?

A

Na+: K+: 2Cl¯ cotransporter (NKCC2 transporter) (allows them inside the cell)

228
Q

What channel is present on the luminal side of the thick ascending limb?

A

Potassium ion channels- potassium ions flow out into the lumen

229
Q

What transporters are present on the basolateral side of the thick ascending limb?

A

Sodium Potassium ATPase pump

Potassium Chloride cotransporter

230
Q

What channels are present on the basolateral side of the thick ascending limb?

A

Chloride

Potassium

231
Q

How else can potassium ions flow from the luminal side to the interstitial fluid?

A

Between the cells in the proximal tubule/ thick ascending limb

232
Q

What happens to potassium ions in the collecting duct?

A

Reabsorbed by the intercalated cells (and distal cells) in exchange for H+
Secreted by Principal cells

233
Q

What are the exit routes for the potassium ions in the principal cells?

A

K+:Cl- cotransporter
ROMK: Renal Outer Medullary K+ channel
BK: Ca2+ activated big-conductance K+ channel

234
Q

What is the difference between sodium and potassium transport pathway?

A

Potassium is filtered, reabsorbed and is secreted. Sodium does not undergo secretion

235
Q

What are the factors affecting K+ secretion by principal cells?

A

Factors affecting Na+ entry through ENaC
Aldosterone
Tubular flow rate
Acid base balance

236
Q

How does Aldosterone affect K+ secretion by principal cells?

A

Stimulates K+ channels as well as sodium channel.

More K+ leaving the principal cells

237
Q

How do tubular flow rates affect K+ secretion by principal cells?

A

High flow rates favour secretion

238
Q

How does acid-base balance affect K+ secretion by principal cells?

A

Acidosis inhibits it

Alkalosis enhances it

239
Q

What is hypokalaemia?

A

plasma potassium ion concentration is less than 3.5mM

240
Q

What is mild hypokalaemia?

A

plasma [K+]- 3.0-3.5mM

241
Q

What is moderate hypokalaemia?

A

plasma [K+]- 2.5-3.0mM

242
Q

What is severe hypokalaemia?

A

plasma [K+] < 2.5mM

243
Q

What causes hypokalaemia?

A

Increased external losses
Redistribution into cells
Inadequate K+ intake

244
Q

What are some examples of increased external losses of K+ ions which causes hypokalaemia?

A

From the GI tract- vomiting, diarrhoea
From the kidney- diuretics, osmotic diuresis, hyperaldosteronism, transporter mutations
From the skin- burns, intense sweating

245
Q

What are some examples of redistribution of K+ ions into cells which causes hypokalaemia?

A

Metabolic Alkalosis

Insulin Excess

246
Q

How does insulin excess cause hypokalaemia?

A

Insulin is released after a meal and bind to the insulin receptor which supports the sodium potassium ATPase pump.
Potassium moves into the cell
Excess insulin –> activity of the transporter increased

247
Q

What are the cardiac symptoms associated with hypokalaemia?

A

Dysrhythmias
Conduction defects
Increased likelihood of dysrhythmias due to digitalis

248
Q

What are the skeletal muscle symptoms associated with hypokalaemia?

A

Weakness
Paralysis
Fasciculations and Tetany

249
Q

What are the GI symptoms associated with hypokalaemia?

A

Ileus
Nausea
Vomiting
Abdominal distention

250
Q

What are the renal symptoms associated with hypokalaemia?

A

Polyuria

251
Q

What is the treatment for hypokalaemia?

A

Eat food which are rich is K+ (bananas, spinach)
KCl administration (oral/i.v.)
Alkalosis correction
Use of K+ sparing diuretics

252
Q

What are some examples of K sparing diuretics?

A

Spironolactone- inhibits aldosterone

Amiloride- inhibits principal cells sodium channels (no potassium secretion)

253
Q

What is hyperkalaemia?

A

plasma potassium ion concentration is more than 5.5 mM

254
Q

What causes hyperkalaemia?

A

Decreased external losses

Redistribution out of cells

255
Q

What are some examples of decreased external loss of K+ that cause hyperkalaemia?

A

Renal Failure
Hypoaldosteronism
Action of drugs

256
Q

What are some examples of redistribution of K+ ions out of cells that cause hypokalaemia?

A

Acidosis (exacerbated by lack of insulin in diabetic ketoacidosis)
Tissue destruction/ cell lysis (e.g.: rhabdomyolysis)

257
Q

What are the cardiac symptoms associated with hyperkalaemia?

A

Dysrhythmias

Conduction disturbances

258
Q

What are the skeletal muscle symptoms associated with hyperkalaemia?

A 
Weakness
Paresthesias
Paralysis
Hyperreflexia
Cramping
259
Q

What are the GI symptoms associated with hyperkalaemia?

A

Nausea
Vomiting
Diarrhoea

260
Q

What is a short term treatment of hyperkalaemia?

A

Calcium IV to antagonise the effect of K+ on heart muscle

261
Q

What is the purpose of short term treatment of hyperkalaemia?

A

Stabilises the cardiac membrane

262
Q

What is an immediate treatment of hyperkalaemia?

A

Insulin and glucose administered to shift K+ into cells

263
Q

What is the purpose of immediate term treatment of hyperkalaemia?

A

Shifts potassium into the cells

264
Q

What is a long term treatment of hyperkalaemia?

A

Diuretics

Treat for renal failure.

265
Q

What is the purpose of long term treatment of hyperkalaemia?

A

Need to increase K+ excretion.

Removal of K+ from the body

266
Q

How is the volume of ECF determined?

A

Total quantity of solute (mainly NaCl- sodium balance)

267
Q

What is the average dietary salt intake?

A

2.3g/day (0.05-25g/day)

268
Q

What is osmolality of the ECF maintained at the expense of?

A

Volume

269
Q

Why is constant plasma osmolality important?

A

The cells will shrink or swell–> severe consequences in the brain

270
Q

What does plasma volume determine?

A

Blood pressure in veins, cardiac chambers and arteries

271
Q

Sodium content is largely regulated by the kidney by controlling:

A

GFR

Sodium reabsorption

272
Q

What is the extrinsic control of GFR?

A

Activation of sympathetic nervous system (baroreceptor response)

273
Q

How does activation of the sympathetic nervous system?

A

Vasocontricts afferent arteriole–> Lowers GFR
Reduced SA of filtration barrier via mesangial cells–> lowers GFR
(Increases renin release)

274
Q

What is the purpose of extrinsic control of GFR?

A

To maintain systemic blood pressure- reduction in GFR will conserve Na+ and H2O–> increase bp/bv

275
Q

What is the intrinsic control of GFR?

A

Autoregulation within kidneys which can control afferent arteriole constriction

276
Q

What are the mechanisms of autoregulation of GFR?

A

Myogenic response by the renal smooth muscle cells that surround arterioles- vasoconstriction in response to stretch
Tubuloglomerular feedback by the juxtaglomerular apparatus- controls vasoconstriction

277
Q

What is the purpose of intrinsic control of GFR?

A

Protects renal capillaries from hypertensive damage and maintains a health GFR

278
Q

How do the afferent arterioles maintain constant capillary pressure and glomerular blood flow?

A

Afferent arterioles constrict when BP is raised and dilate when BP is lowered

279
Q

What sensors are part of the regulatory pathways that control sodium reabsorption?

A

Tubular fluid NaCl concentration receptors within macula densa
Pressure receptors- central arterial tree
Pressure receptors- intrarenal baroreceptors
Volume Receptors- cardiac atria + intrathoracic veins

280
Q

What effector pathways are part of the regulatory mechanism that control sodium reabsorption?

A

Renal sympathetic nerves- stimulate renin release
Direct pressure on kidney
Renin/angiotensis II/ aldosterone- stimulate Na+ reabsorption
Atrial Natriuretic Peptide- inhibits Na+ reabsorption
Dopamine- inhibits Na+ reabsorption

281
Q

Where do the sympathetic nerves of granular cells receive signals from?

A

Baroreceptors in central arterial tree via cardiovascular centre

Principles of Physiology and Pharmacology (7 decks)

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