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Semester 4 > case 7 - teach me physiology > Flashcards

case 7 - teach me physiology Flashcards

1
Q

what is the glomerulus

A

a loop of capillaries twisted into a ball shape, surrounded by the Bowman’s capsule

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2
Q

what occurs in the glomerulus

A

ultrafiltration of the blood, the first step in urine production

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3
Q

what are the three components of the filtration barrier

A

endothelial cells of the glomerular capillaries
glomerular basement membrane
epithelial cells of Bowman’s capsule

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4
Q

what are the epithelial cells of Bowman’s capsule also called

A

podocytes

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5
Q

what are the perforations called in the glomerular capillary endothelium

A

fenestrae which are pores

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6
Q

what does these pores not do

A

they do not restrict the movement of water and proteins or large molecules but instead prevent the filtration of blood cells

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7
Q

what surrounds the luminal surface of the endothelial cells

A

the glycocalyx consisting of negatively charged glycosaminoglycans

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8
Q

what does this glycocalyx function to do

A

functions to hinder the diffusion of negatively charged molecules by repelling them due to like charges

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9
Q

what is the basement membrane that surrounds the capillary endothelium mostly made up

A

type IV collagen, heparan sulfate proteoglycans and laminin

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10
Q

what do heparan sulfate proteoglycans help do

A

help restrict the movement of negatively charged molecules across the basement membrane

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11
Q

what are the three layers of the basement membrane

A

An inner thin layer (lamina rara interna)
A thick layer (lamina densa)
An outer dense layer (lamina rara externa)

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12
Q

what do these layers help do

A

help limit the filtration of intermediate and large sized solutes

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13
Q

what are podocytes

A

Podocytes are specialised epithelial cells of Bowman’s capsule which form the visceral layer of the capsule.

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14
Q

what forms filtration slits

A

foot-like processes project from these podocytes and interdigitate to form filtration slits

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15
Q

what are these filtration slits bridged by

A

a thin diaphragm

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16
Q

what do the pores in this diaphragm stop from corssing

A

proteins

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17
Q

what is the process by which blood filters into the Bowman’s capsule

A

ultrafiltration

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18
Q

what is ultrafiltration

A

simply filtration that occurs under pressure. in this case, the afferent and efferent arterioles are responsible for generating pressure

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19
Q

where is the afferent arteriole

A

at the proximal glomerulus

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20
Q

what does this afferent arteriole do

A

it dilates, while the efferent arteriole at the distal glomerulus constricts

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21
Q

what does this create

A

a pressure gradient throughout the glomerulus, causing filtration under pressue

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22
Q

what is the filtration rate of molecules of the same charge across the filtration barrier inversely related to

A

their molecular weight

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23
Q

what molecules filter less easily

A

Negatively charged large molecules filter less easily than positively charged ones of the same size.

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24
Q

what are the final two segments of the kidney nephron

A

the DCT and the CD

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25
Q

what is the role of the early DCT

A

The role of the early DCT is the absorption of ions, including sodium, chloride and calcium. It is impermeable to water.

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26
Q

what are situated in the first segment of the DCT

A

macula dense

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27
Q

what do the macula densa do

A

they are sensory epithelium involved in tubuloglomerular feedback.

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28
Q

what does this tubuloglomerular feedback allow for

A

allows for control of GFR and blood flow within the same nephron the sente

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29
Q

what is the movement of these ions dependent on in the EDCT

A

Movement of these ions is dependent on the Na+/K+-ATPase transporter on the basolateral membrane of the cells.

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30
Q

what does this excrete

A

this excrete sodium ions into the extracellular fluid, and brings potassium ions into the cell

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31
Q

what does this channel do

A

reduces intracellular sodium levels, creating a gradient which favours movement of sodium into the cell via other channels on the apical membrane

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32
Q

what type of process is this

A

this process is primary active transport, as ATP is directly needed to set up the gradient

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33
Q

what does this sodium concentration gradient generated allow for

A

allows sodium to enter the cell from the lumen of the DCT, which occurs through the NCC symporter alongside chloride ions

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34
Q

what happens to the chloride ions

A

they then exit the cell through a chloride ion uniporter on the basolateral membrane into the extracellular fluid, preventing accumulation within the cell

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35
Q

what inhibit the NCC

A

thiazide diuretics

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36
Q

what also utilises the sodium gradient established in the Na+K+ATPase channel

A

ca2+ absorption

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37
Q

what is the sodium calcium antiporter and where is it found

A

on the basolateral membrane and it is called the NCX channel

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38
Q

what is this channel responsible for

A

This is responsible for transporting calcium ions out into the extracellular fluid, and sodium ions into the cell. The reduction in intracellular calcium creates a gradient which draws calcium ions from the lumen of the tubule into the cell, through a calcium ion uniporter. Since ATP is not directly required, this is secondary active transport.

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39
Q

what also acts here

A

parathyroid hormone - binding of PTH to its receptor causes more Ca2+ channels to be inserted and increases Ca2+ reabsorption

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40
Q

what are the two types of cells in the Late distal convuluted tubule and collecting duct

A

principal cells and intercalated cells

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41
Q

what are principal cells mainly involved in

A

the uptake of sodium ions and extrusion of potassium ions

42
Q

what is this exchange driven by

A

This exchange is, again, driven by a Na+/K+-ATPase on the basolateral membrane This sets up a gradient for sodium to enter the cell through ENaC channels (epithelial Na+ channel).

43
Q

what factors promote secretion of potassium ions into the lumen of the tubule through a potassium uniporter

A

Sodium ions are positively charged, so as they are extruded an electrical gradient is formed. Additionally, potassium ions accumulate within the cell due to the Na+/K+-ATPase.

44
Q

what are intercalated cells

A

they assist in acid-base control, by controlling the levels of hydrogen and bicarbonate ions

45
Q

what do type A intercalated cells do

A

they utilise hydrogen ATPase and H+K+ATPase transporters to secrete H+ into the lumen, whilst reabsorbing bicarbonate

46
Q

what is bicarbonate formed by

A

Bicarbonate is formed intracellularly by carbonic anhydrase acting on carbon dioxide and water (similarly to in the PCT).

47
Q

what is the difference between the PCT and type A intercalated cells

A

is that these cells can actively secrete H+ into the lumen against a large concentration gradient, allowing for H+ secretion in response to acidosis

48
Q

what happens once the hydrogen is in the lumen of the tubule

A

the hydrogen ions react with either phosphate (HPO42-) or ammonia (NH3). This prevents the ions from re-entering the cell, as both new compounds (NH4+ and H2PO4–) are charged. Hence, they are unable to travel back across the membrane, and so are excreted.

49
Q

what prevents an accumulation of chloride ions and potassium ions within the cell

A

a K+/Cl– symporter on the basolateral membrane allows leakage of these ions back into the extracellular fluid.

50
Q

what do type B intercalated cells have

A

have H+ and HCO3– channels on opposite sides of the cell. The net effect in type B cells is secretion of HCO3– and reabsorption of H+, important in the body’s response to alkalosis.

51
Q

what is the main role of the collecting duct

A

is the reabsorption of water, through the action of ADH and aquaporins

52
Q

where is ADH produced and stored and what does it act on to do

A

ADH is produced in the hypothalamus, and stored in the posterior pituitary gland until it is released. This hormone acts on kidney tubules to increase the number of aquaporin 2 channels (water channels) in the apical membrane of collecting duct tubular cells.

53
Q

what does ADH bind to and what does this activate

A

ADH binds to V2 receptors on the tubule cells, which activate adenylyl cyclase hence increasing production of cyclic AMP.

54
Q

subsequently, what happens to the vesicles containing aquaporin 2 channels

A

vesicles containing the aquaporin 2 channels deposit their contents into the apical membrane of the tubular cells (the basolateral membrane always contains aquaporin 3 and 4 channels, so is always permeable).

55
Q

what does ADH also act to do

A

increase urea reabsorption in the medullary collecting duct

56
Q

what is impermeable to water but permeable to urine

A

the thick ascending limb of the nephron

57
Q

what does this result in

A

This means that the urea is able to pass from the interstitium back into the thick ascending limb down its concentration gradient (urea recycling). Whilst in the interstitium, urea acts as an effective osmole and hence allows greater volumes of water to be reabsorbed in the nephron.

58
Q

what are the three parts of the nephron

A

It consists of three parts: the renal corpuscle, the filtering component, the renal tubule, which is responsible for absorption and ion secretion, and the collecting duct, which is responsible for the final reabsorption of water and for storing urine.

59
Q

what are the three parts of the renal tubule

A

The renal tubule has 3 components: the proximal convoluted tubule (PCT), the Loop of Henle and the distal convoluted tubule (DCT).

60
Q

what is the PCT lined with

A

It is lined with simple cuboidal epithelial cells which have a brush border to increase surface area on the apical side. The epithelial cells have large amounts of mitochondria present to support the processes involved in transporting ions and substances.

61
Q

what are the two parts of the proximal tubule

A

pars convolute and pars recta

62
Q

where is the pars convolute and what can it be divided itno

A

The pars convolute resides in the renal cortex and it can further be divided into 2 segments; S1 (segment 1) and the proximal part of S2.

63
Q

what is the pars recta

A

The pars recta is a straight segment present in the outer medulla. It makes up the distal part of S2 and S3.

64
Q

what happens in the PCT

A

A large amount of reabsorption occurs in the proximal convoluted tubule. Reabsorption is when water and solutes within the PCT are transported into the bloodstream. In the PCT this process occurs via bulk transport. The solutes and water move from the PCT to the interstitium and then into peritubular capillaries. The reabsorption in the proximal tubule is isosmotic.

65
Q

what do the proximal tubules reabsorb

A

about 65% of water, sodium, potassium and chloride, 100% of glucose, 100% amino acids, and 85-90% of bicarbonate.

66
Q

what are the two routes through which reabsorption can take place and what do they do

A

paracellular and transcellular. The transcellular route transports solutes through a cell. The paracellular route transports solutes between cells, through the intercellular space.

67
Q

what is the driving force for reabsorption in the PCT and what are the features of this transport

A

The driving force for the reabsorption in the PCT is sodium, due to the presence of many sodium-linked symporters e.g. sodium glucose linked transporters (SGLTs) on the apical membrane. Sodium is usually co-transported with other solutes e.g. amino acids and glucose, or in later segments of the tubule with chloride ions. Thus sodium moving down its concentration allows other solutes to move against their own concentration gradient.

68
Q

how is the electrochemical gradient for sodium created

A

Na+-K+-ATPases on the basolateral surface pump out 3 Na+ ions, in exchange for bringing 2 K+ ions into the cell. This transporter uses primary active transport. This movement of Na+ creates an electrochemical gradient favouring the movement of Na+ into the cell from the tubule lumen.

69
Q

features of the S1 segment of the PCT

A

it is not permeable to urea and chloride ions, hence their concentration increases in S1 which creates a concentration gradient which can be utilised in the S2 and S3 segements.

70
Q

where are the Na+/amino acid symporters located

A

Na+/Amino acid symporters are present on the apical side of cells in the S1 segment of the PCT which reabsorbs all the amino acids in the PCT.

71
Q

where is the Na+/H+ antiporter found

A

on the apical surface of PCT cells. It is an antiporter and therefore transports ions across the cell membrane in opposite directions. In this case, the Na+ ions move into the tubular cells, while the H+ is expelled into the lumen. The primary function of this transporter is to maintain the pH.

72
Q

what happens to the solute concentration as we move along the tubule

A

solute concentration in the tubule decreases while the solute concentration in the interstitium increases

73
Q

what does the difference in concentration gradient in water moving result in

A

The difference in concentration gradient results in the water moving into the interstitium via osmosis. Water mainly takes the paracellular route to move out of the renal tubule but it can also take the transcellular route.

74
Q

what does the PCT secrete

A

organic acids and bases
h+ ions
drugs and toxins

75
Q

features of organic acid and bases secretion

A

bile salts, oxalate and catecholamines (waste products of metabolism)

76
Q

features of hydrogen ions secretion

A

important in maintaining acid/base balance in the body. H+ secretion allows reabsorption of bicarbonate via the use of the enzyme carbonic anhydrase (Fig 2). The net result is for every one molecule of H+ secreted, one molecule of bicarbonate and Na+ is reabsorbed into the blood stream. As the H+ is consumed in the reaction in the tubular lumen, there is no net excretion of H+. In this way, about 85% of filtered bicarbonate is reabsorbed in the PCT (the rest is reabsorbed by the intercalated cells at the DCT/CD later on)..

77
Q

features of drugs/toxins secretion

A

Secretion of organic cations such as dopamine or morphine occurs via the H+/OC+ exchanger on the apical side of the tubule cell, which is driven by the Na+/H+ antiporter.

78
Q

what is the configuration of the Loop of Henle

A

The Loop of Henle has a hairpin configuration with a thin descending limb and both, a thin and thick ascending limb (TAL).

79
Q

what are the features of the limbs of the LoH

A

The thin descending and ascending segments have thin, squamous epithelial membranes with minimal metabolic activity. The TAL has cuboidal epithelial membranes and is quite metabolically active.

80
Q

what is the descending limb highly permeable to

A

water, with reabsorption occurring passively via AQP1 channels.

81
Q

what else is reabsorbed in the descending limb

A

Small amounts of urea, sodium (Na+) and other ions are also reabsorbed. As mentioned above, water reabsorption is driven by the counter-current multiplier system set up by the active reabsorption of sodium in the TAL.

82
Q

what is the thin ascending limb impermeable to and why

A

The thin ascending limb is impermeable to water, due to it having no aquaporin channels.

83
Q

features of Na+ and Cl- reabsorption in the thin ascending limb

A

Na+ reabsorption occurs passively through epithelial Na+ (eNaC) channels and Chloride (Cl–) ions are reabsorbed in the thin ascending limb through Cl– channels. There is some paracellular movement of Na+ and Cl– because of the difference in osmolarity between the tubule and the interstitium.

84
Q

where is the primary site of sodium reabsorption in the LoH

A

the thick ascending limb

85
Q

what is the driver of Na+ reabsorption

A

Sodium reabsorption is active – the driver is the Na+/K+ ATPase on the basolateral membrane which actively pumps 3 Na+ ions out of the cell and 2 potassium (K+) ions into the cell. So by creating a low intracellular concentration of sodium, the inside of the cell becomes negatively charged, creating an electrochemical gradient.

86
Q

what then happens to sodium

A

Sodium then moves into the cell (from the tubular lumen) down the electrical and chemical gradient, through the NKCC2 transporter on the apical membrane This transporter moves one Na+ ion, one K+ ion and two Cl– ions across the apical membrane.

87
Q

what happens to the potassium ions

A

Potassium ions are transported back into the tubule by renal outer medullary potassium (ROMK) channels on the apical membrane to prevent toxic build up within the cell.

88
Q

what happens to the chloride ions

A

Chloride ions are transported into the tissue fluid via CIC-KB channels.

89
Q

what are the overall effects of the processes in the thick ascending limb

A

Removal of Na+ whilst retaining water in the tubules – this leads to a hypotonic solution arriving at the DCT.
Pumping Na+ into the interstitial space – this contributes to a hyperosmotic environment in the kidney medulla

90
Q

what happens in the glomerulus to water and describe the process

A

In the glomerulus, water is initially filtered out, along with the other solutes e.g. Na+, K+ and glucose. From here H2O needs to be reabsorbed into the tubule cells and then back into the interstitial space. From the interstitial space, H2O can move back into the vasa recta, the blood vessels running alongside the nephron.

91
Q

where are the 3 main places where H2O reabsorption accurs

A

the proximal convoluted tubule (PCT), the descending limb of the Loop of Henle and the collecting ducts.

92
Q

what happens to H20 when Na+ movement makes the tubule intracellular fluid more concentrated than the filtrate

A

This creates a concentration gradient to drive H2O movement into the tubule cell. This is known as transcellular movement and occurs when H2O molecules move across the cell membrane via aquaporin-1 (AQP-1) channels, driven by osmosis.

93
Q

what happens once the H2O molecules are in the cell

A

Once in the cell, H2O molecules then move out of the cell into the cortical interstitial space via another AQP-1 channel on the basolateral surface.

94
Q

what is the paracellular movement of H20

A

Paracellular movement of H2O occurs between tubule cells and is due to the higher hydrostatic pressure in the filtrate than in the interstitial space. This forces water between the tubule cells through leaky tight junctions.

95
Q

what is the transcellular movement of H20

A

Transcellular movement of H2O effectively bypasses the tubule cell and moves it straight from the filtrate to the interstitial space directly.

96
Q

what is the result by the end of the PCT

A

By the end of the PCT, the concentration of water in the filtrate and interstitial space is almost the same. Overall, about 67% of the filtered water is reabsorbed in the PCT.

97
Q

where does water reabsorption occur in the loop of henle

A

Water reabsorption occurs in the thin descending limb of the Loop of Henle. It is permeable to water, which means that H2O molecules are freely able to leave it. Similarly to in the PCT, water can leave the thin descending limb into the more concentrated medulla through transcellular and paracellular movement.

98
Q

what is the driving force behind the movement of water out into the medulla

A

The driving force behind this is the movement of Na+, Cl– and K+ from the tubule to the medulla, via NKCC symporters in the thick ascending limb. This makes the renal medulla more concentrated, providing an osmotic gradient.

99
Q

what is water reabsorption driven by in the collecitng duct

A

In the collecting duct, H2O reabsorption is driven by antidiuretic hormone (ADH). ADH is produced in the hypothalamus and is secreted from the posterior pituitary gland in response to low plasma volume or high osmolality.

100
Q

where does ADH act and what does this trigger

A

ADH acts on the principal cells in the collecting duct by binding to receptors. This triggers an intracellular signalling pathway that causes increased aquaporin-2 (AQP-2) production for the apical surface of the principal cell. The water can then move through the tubule and back into the renal medulla. Similarly to in the Loop of Henle, the force driving this movement is the high concentration of Na+ in the renal medulla.

101
Q

how does blood move from the interstitial space back into the circulation

A

via the vasa recta

102
Q

what does the concetrated vasa recta result in

A

water moves into it via osmosis

Semester 4 (80 decks)

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