1
Q
what is the first step in urine formation?
A
glomerular filtration
2
Q
what is filtered into filtrate in glomerular filtration and what isn’t?
A
- filtrate contains fluids, electrolytes and other solutes (glucose, amino acids, urea, creatinine)
- plasma proteins are not filtered
3
Q
what 3 processes are involved in urine formation and in what order?
A
- filtration
- reabsorption
- secretion
all lead to excretion
4
Q
describe a feature of tubular cells and explain how this relates to function
A
- tubular cells are polarised
- this means the membranes on different sides of the cells do different things allowing for movement of solutes / fluids etc.
5
Q
what is meant by the basolateral and apical membranes of tubular cells?
A
basolateral membrane = interstitial side
apical membrane = lumen side
6
Q
what is labelled 1-5 in the diagram?
A
- luminal membrane
- cytosol
- basolateral membrane
- interstitial fluid
- capillary wall
7
Q
in which direction (1 to 5 / 5 to 1) do reabsorption and secretion occur?
A
reabsorption = 1 to 5
- reabsorption occurs from tubule to blood
secretion = 5 to 1
- secretion occurs from blood to tubule
8
Q
how do hydrophilic molecules cross membranes?
A
via channel or carrier transporters
9
Q
describe and explain what diffusion is and the different types
A
- movement down a concentration or electrochemical gradient
- can be simple or facilitated
- facilitated = using channels / carriers
- simple = doesn’t require membrane proteins
- diffusion of water = osmosis
10
Q
describe and explain what active transport is and the different types
A
- movement against a concentration or electrochemical gradient
- primary = coupled directly to an energy source (e.g. ATP)
- secondary = coupled indirectly to an energy source
11
Q
what is Tm in relation to transport across membranes? what will occur when Tm is reached?
A
- transport maximum
- capacity of carrier is exceeded
- excess substance will be excreted (stays in filtrate and not reabsorbed)
12
Q
what kinds of molecules are transported by simple diffusion vs facilitated diffusion?
A
simple
- gases, lipophilic substances (including glycerol, steroid hormones)
facilitated
- large polar / charged molecules
13
Q
label this image
A
14
Q
what is meant by a uniporter, symporter and antiporter in terms of what they transport and how?
A
- uniporter = transports 1 molecule
- symporter = 2 molecules in 1 direction
- antiporter = transports 2 molecules in opposite directions
15
Q
what is bulk flow?
A
- aka solvent drag
- flow of water moves solutes with it in large quantities
- solutes in the ultrafiltrate are transported back from the renal tubule by the flow of water
- various constituents are moved together in bulk
16
Q
label this image (ignore blue box, just black lines)
A
17
Q
describe and explain the function of the PCT
A
- primary site of reabsorption
- for all solutes, dependent on action of Na+/K+ ATPase
18
Q
label the image with the processes occurring and the names of the vessels they are occurring between
A
19
Q
what kinds of transport processes are occurring in reabsorption and secretion? explain
A
active processes mainly
organic anion transport (OA-)
- e.g. bile salts, urate / uric acid
organic cation transport (OA+)
- e.g. adrenaline, noradrenaline, dopamine
20
Q
give some example of drugs that are transported in reabsorption / secretion by organic anion / cation transporters
A
diuretics (OA-)
penicillins (OA-)
opioids (OA+)
21
Q
what happens to useful substances (water, electrolytes etc.) when they pass into the renal tubules in the filtrate? how?
A
- they are selectively reabsorbed from the filtrate back into the blood in the PCT
- reabsorption of some substances is passive while some is active
- water is mostly reabsorbed by osmosis
22
Q
where does tubular secretion take place and how?
A
- tubular secretion takes place from the blood in the peritubular capillaries to the filtrate in the renal tubules
- because of the short time within the glomerulus, some substances are not filtered out of the blood
- this includes drugs that are extensively bound to plasma proteins
- such substances are therefore cleared by secretion
23
Q
how is the sodium gradient into the tubular cell across the apical membrane in the PCT maintained?
A
- basolateral Na+/K+ pump pumps sodium out of the cell towards plasma and potassium moves in
- Na+/K+ pump is an antiporter
- 3 Na+ out, 2 K+ in, ATP hydrolysed
this creates the Na+ gradient for reabsorption of solutes and water form tubular lumen
24
Q
where does the energy come from to move H+ out of the tubular cell at the apical membrane?
A
energy for H+ transport out comes from Na+/K+ ATPase that pumps Na+ out on basolateral membrane
25
describe and explain what ATPase does in the PCT reabsorption
- moves sodium against conc gradient
- moves potassium against its conc gradient
- it is an energy-dependent antiporter (ATP is hydrolysed for the energy release)
26
how does ATPase move sodium against its concentration gradient from the tubular lumen in PCT reabsorption?
- inside of tubular cell has low sodium
- causes sodium to move in and protons to move out of tubular cells by Na+ / H+ antiporter (secondary active transport)
- allows for sodium reabsorption from the tubular lumen
27
describe and explain the process for how bicarbonate ions are reabsorbed into the blood from the tubular lumen
- there is a Na+ / bicarbonate ion symporter on basolateral membrane for reabsorption into blood but there are no bicarbonate transporters on apical membrane
- H+ from cell couples to bicarbonate to form carbonic acid in tubular lumen which dissociates into water and CO2
- CO2 moves back into tubular cell to provide more carbonic acid
- proton cycles back and forth
- no transporter for bicarbonate ion means it must travel between the lumen and cell as CO2
28
describe the type of transport Na+ / glucose transporter performs
- it is located in the apical-luminal membrane
- it is a symporter
- performs secondary active transport because it is indirectly linked to the energy source of ATPase antiporter
29
summarise the action of Na+ in action reabsorption (secretion) in the PCT
- Na+ / K+ ATPase pump hydrolyses ATP to ADP
- 3 Na+ transported out of tubular cell
30
summarise the action of K+ in action reabsorption (secretion) in the PCT
- 2 K+ transported from the interstitial fluid into the tubular cell
- at the same time as 3 sodium ions are transported out of tubular cell
31
summarise the action of glucose and amino acids in action reabsorption (secretion) in the PCT
transported by the symporters
- Na+ / glucose
- Na+ / amino acids
32
summarise the action of H+ / HCO3- in action reabsorption (secretion) in the PCT
H+ + HCO3- ↔ H2CO3 ⬌ H2O + CO2
HCO3- is reabsorbed and H+ is secreted
33
H+ + HCO3- ↔ H2CO3 ⬌ H2O + CO2. what is the bold arrow reaction catalysed by?
carbonic anhydrase
34
what substances are passively reabsorbed in the PCT?
water
Ca2+, Cl-, K+ (some Na+)
urea
35
describe and explain the passive reabsorption of water in the PCT
- osmosis
- primarily through 'leaky' tight junctions (paracellular movement) and also via water channels (aquaporins)
- high water permability due to large number of aquaporins in basolateral and apical-luminal membranes
- water reabsorption facilitated by osmotic gradient from Na+ reabsorption and aquaporins
36
how are Ca2+, Cl- and K+ (and some Na+) passively reabsorbed in the PCT?
via paracellular transport
37
how is urea passively reabsorbed in the PCT?
- around 50% of urea is reabsorbed in PCT
- much of this is via bulk flow movement with water
38
describe and explain the role of the loop of Henle in reabsorption
- important role in NaCl and water reabsorption
- creates hyperosmotic renal medullary interstitium
- hyperosmotic = lots of solutes which provides osmotic gradient for water reabsorption
39
what does the loop of Henle have a large role to play in?
concentration of urine
40
what forms the juxtaglomerular apparatus?
macula densa with granular cells
41
where is the juxtaglomerular apparatus located? what is it involved in?
- located at point where DCT passes the fork formed by afferent and efferent arterioles
- involved in the tubuloglomerular feedback mechanism
42
what are juxtaglomerular granular cells, what are they a source of and where are they present?
- they are modified smooth muscle cells
- believed to be the source of renin
- present in the vascular component (most numerous in the afferent arteriole)
- located close to the macula densa
43
what does autoregulation of renal blood flow and GFR do?
maintains a constant renal blood flow and glomerular filtration rate (GFR) over the physiological range of mean arterial pressure
44
what is the physiological range of mean arterial pressure (MAP) and how does it affcet renal blood flow and GFR?
- MAP = 80-180 mmHg
- a few % change in BF and GFR (minimal effect)
45
what is autoregulation of renal blood flow and GFR 'protective' against?
- hypertensive irreversible renal damage
- hypotensive ischaemia
46
how does the kidney 'autoregulate'? explain
- can autoregulate quite rapidly in response to a change in BP by adjustment of diameter of the afferent arteriole
- this is myogenic and known as tubuloglomerular feedback
47
what is meant by the terms myogenic and tubuloglomerular feedback?
myogenic
- intrinsic
- resist stretch of vascular walls and diameter change by contracting
- thought that stretch of vascular wall increases movement of calcium into cells = contraction (prevents over-distension)
tubuloglomerular feedback
- rapid autoregulatory process where macula densa cells in DCT sense increased NaCl conc
- this then causes afferent arteriole to constrict
48
describe and explain tubuloglomerular feedback when arterial pressure is high
- increase in BP = increased pressure in glomerulus = increased GFR
- filtrate forms more quickly so flow rater increases in LoH
- macula densa senses increased NaCl due to increased GFR and less reabsorption time
- macula densa cells secrete paracrine vasoactive agents into interstitial fluid in response to increased NaCl in filtrate (act on vascular smooth muscle cells, particularly in afferent arteriole)
49
how is high GFR reduced to normal? explain
- by vasoconstriction of afferent arterioles
- this decreases blood flow into the glomerulus
50
what 2 processes lead to vasoconstriction (VC) and therefore allow for autoregulation to lower high GFR?
- myogenic afferent arteriole (stretch leads to VC)
- tubular glomerular feedback (adenosine / ATP leads to VC)
51
why does the vasoconstriction of the afferent arteriole lower GFR in autoregulation?
- it decreases hydrostatic pressure in glomerulus
- this then decreases net filtration pressure
- ultimately this decreases GFR to get it back into the narrow set range we want to maintain
52
describe and explain tubuloglomerular feedback when arterial pressure is low
- less flow rate = more reabsorption of Na and Cl ions (more time in LoH)
- lower conc of NaCl detected by macula densa cells
- NO is secreted by macula densa cells = vasodilation of afferent arteriole
- macula densa cells also communicate to the granular cells in the afferent and efferent arterioles to secrete renin (stimulates angiotensin II which constricts efferent arteriole to return GFR to normal)
53
explain specifically tubuloglomerular feedback when the arterial pressure is low in terms of key points and how GFR is increased
- drop in arterial pressure = drop in GFR
- decreased flow in LoH = more reabsorption of Na+ and Cl-
- macula densa cells detect lowered Na+ and Cl- conc
- NO secreted by macula densa (vasodilation of afferent arteriole)
- macula densa cause granular cells in afferent and efferent arterioles to secrete renin (stimulates angiotensin II to constrict efferent arteriole)
54
how is low GFR increased back to normal?
- by vasodilation of afferent arterioles
- this increases blood flow into glomerulus
- also efferent arteriole vasoconstriction by angiotensin II
55
what 2 processes lead to vasodilation (VD) and therefore allow for autoregulation to increase low GFR?
- myogenic (less stretch = relaxation of afferent arteriole)
- tubuloglomerular feedback (NO = VD)
56
what is the early DCT permeable and impermeable to and therefore what does it reabsorb?
- early DCT reabsorbs Na+, K+ and Cl-
- is virtually impermeable to H2O and urea
57
what are the late DCT and CD composed of? explain what they reabsorb and secrete
- composed of principal (P) and intercalated (I) cells
- P cells reabsorb Na+ and secrete K+
- I cells reabsorb K+ and HCO3- and secrete H+
58
describe and explain the diagram showing early DCT reabsorption including the movement of Na+, K+, Cl- and H2O
59
describe and explain the diagram showing late DCT and CD reabsorption (P cell specific) including the movement of Na+, K+ and Cl-
60
describe and explain the reabsorption in late DCT and CD (P cell specific) including the movement of Na+, K+ and Cl-
- reabsorption of Na+
- secretion of K+
- low cellular sodium conc = sodium enters tubular cell via sodium ion selective channels
- high cellular conc of K+ = secretion of K+ back into tubular lumen for excretion via the filtrate
61
describe and explain the actions of aldosterone and ADH in reabsorption in the late DCT and CD
aldosterone
- increase Na+ (and water) reabsorption
- increase K+ secretion
ADH
- increased permeability to water
= increased reabsorption
62
describe and explain the diagram showing late DCT and CD reabsorption (I cell specific) including the movement of K+, HCO3-, HCO2, H+ and CO2
63
describe and explain the reabsorption in the late DCT and CD (I cell specific) including the movement of K+, HCO3-, HCO2, H+ and CO2
- reabsorption of HCO3- and K+
- secretion of H+
- reabsorption of bicarbonate is same as in PCT
64
how are bicarbonate ions reabsorbed in the PCT and late DCT / CD? (it is the same way in each)
- carbonic acid made in tubular lumen
- converts to water and CO2
- CO2 passes through apical-luminal membrane
- combines with water to reform carbonic acid
- dissociates into bicarbonate ion for reabsorption into capillary via ATPase
65
describe and explain the action of aldosterone in the reabsorption in the late DCT and CD
stimulates H+ secretion through both ATPase transporters on apical-luminal membrane
66
describe and explain (with a diagram) the fate of Na+ ions in the body with typical diet and normal blood volume (euvolaemia)
67
how does fate of Na+ change with extracellular fluid volume expansion (increased blood volume)? explain
- reduced ADH and RAAs
- increased ANP / BNP (natriuretic peptides)
- reduced Na+ reabsorption, more Na+ excreted
68
how does fate of Na+ change with extracellular fluid volume contraction (decreased blood volume)? explain
- increased ADH and RAAs
- decreased ANP / BNP (natriuretic peptides)
- increased Na+ reabsorption (water follows to be retained and corrects low blood volume)
69
why do we excrete minimal salts?
because we need sodium ions in our interstitial fluids
70
describe and explain (with a diagram) the typical fate of glucose in the body
typically 0% excreted
71
describe and explain (with a diagram) the fate of glucose in the body if plasma [glucose] ≥ 10 mmol/L
glucose amount exceeds transport maximum for the sodium-glucose transporters
