Renal Anatomy and Disease Flashcards
(91 cards)
1
Q
How much body weight of an average person is water?
A
- 50-70% (normally 60%)
- in an average person of 70kg is 42L
2
Q
where is water found in the body?
A
- in the intracellular compartment or the extracellular compartment
3
Q
how much water is in the intracellular fluid?
A
- 62% of the total volume of water in the body
- 25-30L
4
Q
how much water is found in the extracellular fluid compartments?
A
- plasma = 7%, 3-4L
- interstitial fluid = 28%, 11-12L
- transcellular = 3%, 1.5-2L
5
Q
what are the cationic concentrations of ICF and ECF?
A
ICF:
- K+ conc = 148mM
- Na+ conc = 10mM
ECF:
- K+ = 5mM
- Na+ = 140mM
- this creates conc gradients for K+ to move out of the cell, and Na+ to move into the cell
- transport pathways are driven by channels and carriers
6
Q
what are the anionic concentrations of ICF and ECF?
A
ICF:
- Cl- = 4mM
- protein = 55mM
ECF:
- Cl- = 103mM
- protein = 15mM
- plasma contains lots of proteins which cannot pass the capillary endothelium as they are too large
7
Q
what does the total amount of Na+ in the plasma create?
A
- the effective circulating volume/ECF volume
- volume of plasma can change which can impact blood pressure
- changes in plasma are due to renal control as the kidney must handle sodium correctly
8
Q
what are the typical inputs and outputs of Na+ daily?
A
daily input = 150mM due to diet
- this input of 150 mM must be excreted to stay in balance
- we lose 10mM per day in stool and sweat
- we lose 140mM per day in urine via kidney
9
Q
what are the typical inputs and outputs of water per day?
A
daily input = 2.6L (1.2L in drink, 1L in food, 0.35L from metabolism)
- we lose 1.1L per day via respiration, stool and sweat
- we lose 1.5L per day via urine
- kidney plays major role in water balance as it is the major route of excretion
10
Q
what happens if we cannot excrete the sodium and water we have consumed daily?
A
- sodium becomes accumulated in plasma which changes the ECF volume and therefore changes blood pressure
- if we cannot excrete water, there is an expansion of the ECF volume and heightened blood pressure
- excess fluid can accumulate in tissues which can affect lung function
11
Q
why are kidneys critical?
A
- they control excretion of sodium and water
12
Q
what is the general morphology of the kidney?`
A
- 10cm x 5.5cm
- located between T12 and L3 vertebrae
- renal arteries bring blood to kidney, renal veins take blood away
- renal pelvis leas to ureter which leads to bladder for urine storage
- 150 grams
13
Q
what is renal agenesis?
A
- occurs in 1/2500 foetuses
- kidneys fail to form
- incompatible to life
- high risk of miscarriage if lack of kidney development
14
Q
what is ectopic kidney?
A
- occurs in 1/800 post-birth
- kidneys are not formed in the correct place of the body e.g. in the pelvis
- causes increased risk of damage and stone formation
15
Q
what is horseshoe kidney?
A
- occurs in 1/1000 individuals
- both kidneys form but are fused across the midline, forming one kidney
- increased chance of damage and stone formation
16
Q
what structures can be seen in the longitudinal cross-section of the kidney?
A
- capsule: thin fibrous layer around the kidney for structural integrity
- cortex: in the light area, below the capsule
- medulla: in dark area, beneath the cortex
- contains medullary rays
- stripes represent highly capilliarised blood supply
17
Q
what is the nephron?
A
- functional unit of the kidney
- 1-1.5 million per kidney
18
Q
what is the structure of the nephron, and the route of fluid through the nephon?
A
- Bowman’s capsule (BC) surrounds the glomerulus
- an afferent arteriole brings blood to the glomerular capillary bed:
1. plasma is filtered and moved out into BC
2. any fluid that isn’t filtered leaves via efferent arteriole - once in BC, filtrate moves down into nephron:
1. ultrafiltrate moves through the Proximal tubule, through Loop of Henle, then through the Distal tubule into the Collecting Duct
2. collecting duct drains 6 distal tubules to form urine
3. urine is formed for storage in the bladder
19
Q
what are the two types of nephron?
A
- Superficial nephron (85%)
2. Juxtamedullary nephron (15%)
20
Q
what is the superficial nephron?
A
- nephrons which sit with glomerulus and BC at the periphery of the cortex
- Loops of Henle enter the outer medulla and drain into the collecting duct
- make up 85% of total nephrons in kidney
21
Q
what is the juxtamedullary nephron?
A
- where the glomerular beds and BCs sit at the fringe of the medulla
- they have deep Loops of Henle that penetrate the medulla
- distal tubules drain into the collecting duct
- these nephrons play biggest role in concentrating urine
- make up 15% of all nephrons in the kidney
22
Q
what is renal failure?
A
- a fall in glomerular filtrate rate (GFR)
- leads to an increase in serum urea and creatinine
23
Q
what is acute real failure?
A
- reversible
- history is short
- no change to haemoglobin
- kidney size stays the same
- there is no peripheral neuropathy
24
Q
what is chronic renal failure?
A
- irreversible: dialysis or transplant is needed
- progressive
- long history
- drop in haemoglobin levels
- kidney size decreases due to damage
- involves peripheral neuropathy
25
what is peripheral neuropathy?
- peripheral nerve damage leading to problems with sensation and movement
- damage to sensory and motor neurons
26
how does chronic renal failure progress?
- thickening of glomerular membranes
- damage to glomeruli capillary beds
- glomerulosclerosis: scarring of glomeruli
- tubular atrophy: dying off nephrons
- interstitial inflammation
- fibrosis
- reduction in renal size
27
what is uraemia?
- term to describe the group of severe symptoms of kidney failure
28
what are the uraemia symptoms of chronic renal failure?
1. failure to excrete salt and water
- leads to high BP, hyperkalaemia (increased K+) and mild acidosis
2. poor excretion of urea/creatinine and leakage of protein into urine
- loss of plasma proteins, anorexia, nausea, vomiting, neuropathy, pericarditis (inflamed pericardium)
3. failure of erythropoietin production:
- kidney normally produces this hormone to form haemoglobin
- loss of hormone causes anaemia and lethargy
4. failure to excrete phosphate
- high phosphate levels lower serum Ca2+ conc by precipitation
- leads to itchy skin and osteoporosis (brittle bones)/osteomalacia (soft bones)
29
what is precipitation by phosphate?
- metabolic calcification
- calcium phosphate is deposited in soft tissues
- causes pruritus (itchy skin) and bone disease
30
what is the normal GFR?
125ml/min
31
what are the causes of chronic renal failure?
- 30% cases from glomerulonephritis (kidney infection)
- 25% cases from diabetes mellitus
- 10% caused by hypertension
- 5% caused by polycystic kidney disease (inherited)
- 10% cases unknown
32
how can chronic renal failure be treated?
1. treating reversible factors by restricting protein, salt and water in diet
2. taking phosphate binders: take up excess phosphate
3. taking sodium bicarbonate: combat acidosis
4. give diuretic drugs: excrete more sodium and water
- all 4 of these treatments attempt to reduce symptoms and slow progression
- these do not reverse the illness as it is chronic
5. dialysis and transplantation is needed at severe level: GFR <5-10ml/min
33
where does filtration occur?
- in the glomerulus and glomerular capillaries
- blood plasma enters capillary bed via afferent arteriole
- any unfiltered plasma leaves via efferent arteriole to peritubular capillaries
34
where does urine formation occur?
- ultrafiltrate moves down the nephron and is modified by proximal, LoH, distal and collecting
- at end of collecting duct, urine is formed, stored in the bladder and excreted
35
what is glomerular filtration?
% of plasma that moves from the capillary to the nephron in the BC, to form ultrafiltrate
36
what is tubular reabsorption?
- ions, solutes and water leave through the tubular lumen of the nephron and enters the peritubular capillaries
- peritubular capillaries return this fluid to the venous blood supply
37
what is tubular secretion?
- when substances in the peritubular capillaries are secreted across renal epithelial cells into tubular fluid and lost in urine
38
what is the glomerulus and how is it involved in filtration?
- glomerulus is a capillary bed
- diameter = 200nm
- plasma comes in the afferent arteriole to the capillary bed
- 20% plasma is filtrated into BC (180L/day)
- 80% goes through efferent arterioles to peritubular capillaries into venous blood
- forms ultrafiltrate
plasma volume is 3L, so glomerulus filters a volume 60x the plasma volume (180L/day)
39
what does filtration permit and restrict?
permits: H20 and small molecules
- ions, solutes, glucose, amino acids
restricts: blood cells and proteins
40
what is contained in the ultrafiltrate?
- protein-free plasma
| - 1% albumin is filtered: small molecular weight proteins which are reabsorbed at the proximal tubule
41
what is the transcellular pathway of tubular transport?
- across cell
- reabsorption: ions, solutes and water which use transport proteins to move across apical and leave via basolateral membranes to enter the peritubular capillary
- secretion: transport proteins are used to move solutes from peritubular capillary and interstitial fluid from basolateral, to apical, and into the lumen
42
what is the paracellular pathway of tubular transport?
- between cells via tight junctions
- lets ions, solutes and water move between them
- reabsorption = from tubular fluid into peritubular capillary
- secretion = from peritubular capillary into tubular fluid
43
what is the Proximal Tubule?
- bulk reabsorbing epithelium: reabsorption of 70% of the filtrate
- 70% H2O and Na+ are filtered by glomerulus and reabsorbed by PT
- 100% glucose and amino acids are reabsorbed
- 90% bicarbonate is reabsorbed
44
what is transported at the basolateral membrane of the proximal tubule?
1. Sodium-potassium ATPase
- transports 3Na+ out and 2K+ in using ATP hydrolysis
- moves ions against electrochemical forces
- maintains low intracellular Na+ to form conc gradient for Na+ to move across apical side
2. potassium channel
- sets up driving force for Na+ uptake at apical membrane
- sets negative membrane potential as K+ leaves the cell
- K+ leaves the cell through this channel
45
what is transported at the apical membrane of the proximal tubule?
1. sodium-glucose cotransport protein (SGLT1, SGLT2)
- uses Na+ gradient from Na-K ATPase to bring glucose into cell
- glucose moves against conc gradient across apical membrane
- glucose is then absorbed into peritubular capillary at basolateral side down conc gradient via facilitated diffusion
2. Sodium-amino acid cotransporters (same as glucose)
3. NaPiII (sodium-phosphate cotransporter)
- binds sodium and phosphate
- uses the electrochemical force of Na+ to bring phosphate into cell
- phosphate diffuses across basolateral membrane into peritubular capillary
46
what happens to Na+ that enters the proximal tubule from the cotransporters?
- they are moved out by the Na-K ATPase on the basolateral membrane to maintain low intracellular sodium
reabsorption of sodium drives water reabsorption
47
what happens to the phenotype of mice when NaPiII is knocked out?
mice cannot make the NaPiII protein:
- less phosphate reabsorption
- decreased plasma-phosphate levels due to phosphate being lost in the urine
there is more phosphate in the tubular fluid:
- causes increased calcification due to precipitation, leading to the formation of intraluminal stones (nephrolithiasis)
- deposits renal parenchyma (nephrocalcinosis)
- causes renal damage
48
how does bicarbonate reabsorption occur at the proximal tubule?
NHE3 (sodium-hydrogen exchanger) on apical membrane:
- as Na+ enters cell, H+ leaves
- H+ that leaves binds to bicarbonate to form carbonic acid
- carbonic anhydrase causes carbonic acid to dissociate to CO2 and H2O at apical membrane
- CO2 diffuses into the cell down conc gradient
- H2O moves into cell via aquaporins
- inside the cell, carbonic anhydrase in the ICF forms recombines CO2 and H2O to form carbonic acid
- carbonic acid forms bicarbonate
bicarbonate and sodium are reabsorbed at the basolateral membrane by a cotransporter
- one bicarbonate and 3Na+ enter the peritubular capillary
- bicarbonate maintains pH in the plasma
49
what happens to the phenotype of mice when NHE3 is knocked out?
mice cannot reabsorb bicarbonate due to lack of H+ secretion:
- causes acidosis, so plasma is reduced by 0.1pH, which impacts electrolytes
- impacts systole in cardiac cycle due to lack of Na+ reabsorption
- mice lose more fluid
50
why does losing NHE3 cause major issues?
- inhibition of H+ secretion
- inhibition of sodium and bicarbonate reabsorption
- fall in fluid reabsorption
- drop in plasma bicarbonate, leading to acidosis
- fall in BP due to decrease in ECF volume as lack of water reabsorption
51
what is the transport maximum?
- rate of transport has a maximum limit as there are a limited number of protein carriers in the cell membrane
example: increase in plasma glucose causes increase in rate of filtration
- at a certain point, whatever is being filtered is reabsorbed, so nothing appears in the urine
- transport max of glucose = 375mg/min
52
why can some glucose appear in the urine? what is it an indication of?
- when reabsorption becomes constant
- the renal threshold is extrapolated due to plasma glucose level being above glucose in the urine
- this threshold can indicate diabetes mellitus
53
how does secretion occur in the proximal tubule?
2 systems:
- organic cations
- organic anions
- rapid removal of compounds via excretion
- removal of plasma protein-bound substances of peritubular capillaries to tubular fluid
- removal of foreign compounds e.g. penicillin (not always helpful)
54
why is a high dose of penicillin needed when treating an antibiotic infection?
- the proximal tubule filters it into the urine very quickly
55
what is the role of the Loop of Henle?
- concentrates the urine
- reabsorption of Na+, Cl- and H2O
- reabsorption of Ca2+ and Mg2+
- site of action of loop diuretics
56
what are diuretics?
- class of drug which increases urine flow rate to lose excess fluid
57
what are the 3 structures of the loop of Henle?
1. thin descending limb
- water permeable
- impermeable to Na+ and Cl-
2. Thin ascending limb
- permeable to Na+ and Cl-
- impermeable to water
3. thick ascending limb
- permeable to Na+ and Cl-
- impermeable to water
58
what is transported at the basolateral membrane of the Thick Ascending Limb of the Loop of Henle?
1. Sodium-potassium ATPase
- sets up driving force for influx of sodium across the apical membrane
- maintains low intracellular sodium
2. Barttin-CLCK chloride channel
- Barttin is a protein beta-subunit which transports CLCK to basolateral membrane of TAL
- CLCK is a channel which allows chloride to diffuse into the peritubular capillary via facilitated diffusion
- allows for absorption of NaCl
- Ca2+ and Mg2+ are absorbed by paracellular transport as they follow NaCl
59
what is transported at the apical membrane of the thick ascending limb of the Loop of Henle?
1. NKCC2: Na-K-Cl cotransporter
- uses Na+ electrochemical force to bring 2Cl- and K+ into cell
- Na+ is reabsorbed into peritubular capillary via Na-K ATPase on basolateral membrane
- Cl- is reabsorbed by CLCK on basolateral membrane
- drives transport of water
2. ROMK: potassium channel
- K+ is recycled at the apical membrane into tubular fluid
- this sets up the negative membrane potential across apical membrane for TAL to function
- if there is not enough K+ in tubular fluid, NKCC2 cannot work
60
what is Bartter's syndrome?
- mutation of the thick ascending limb
- recessive genetic mutation: inherited
symptoms:
- saltwasting and polyuria due to lack of NaCl and H2O reabsorption
- decrease in ECF volume -> hypotension
- hypokalaemia: low K+ plasma
- metabolic alkalosis
- hypercalciuria: increased Ca2+ in urine due to less reabsorption of Ca2+ and Mg2+ due to less NaCl reabsorption
- nephrocalcinosis
61
what causes Bartter's syndome?
Loss of function mutations:
1. Mutation in NKCC2 causes inability to reabsorb NaCl
2. CLCK mutation leads to accumulation of Cl- in the cell
- high intracellular Cl- conc stops NKCC2 from working
- this stops reabsorption of NaCl
3. ROMK mutation means K+ cannot be recycled across apical membrane, so there is less K+ in tubular fluid
- this stops NKCC2 function so less NaCl reabsorption
62
what happens to the phenotype of mice when ROMK is knocked out?
these mice cannot make the ROMK channel:
1. salt wasting: fractional excretion of Na+ and Cl- is high as K+ is no longer recycled on apical
- causes loss of NaCl in urine
2. polyuria: urine flow is higher
- knockout mice lose more water due to less NaCl reabsorption
3. mice have acidosis rather than alkalosis which humans have
- there is no difference in wildtype and knockout mice in plasma K+
- doesn't fully reflect human patients with lack of ROMK
63
what are 2 examples of loop diuretics and what do they do?
- both inhibit NKCC2 to inhibit NaCl reabsorption and water reabsorption
- cause an increase in urine flow rate
- lower ECF volume to treat high blood pressure
- have Bartter's-like symptoms so must be dosed correctly to avoid hypotension
64
what is the role of the early distal tubule?
1. reabsorption of NaCl
2. reabsorption of Mg2+
sensitive to thiazide diuretics
65
what is transported at the basolateral membrane of the early distal tubule?
1. sodium-potassium ATPase
- uses ATP to maintain low intracellular Na+ conc by exchanging 3Na+ out of cell for 2K+ into cell
2. K+ channel
3. CLCK
66
what is transported at the apical membrane of the early distal tubule?
1. NCC: sodium-chloride cotransporter
- Na+ across apical membrane is driven by the electrochemical gradient
- binds Na+ and Cl- and undergoes conformational change to bring them into the cell
Na+ is reabsorbed by Na-K ATPase
Cl- is reabsorbed by CLCK
2. Magnesium channels
- located on apical membrane, but there are no magnesium transporters on the basolateral membrane
- it is unknown how magnesium is reabsorbed
67
what is Gitelman's syndrome?
- recessive genetic mutation in NCC (inherited)
- salt wasting and polyuria
- hypotension
- hypokalaemia
- metabolic alkalosis
- hypocalciuria (different to Bartter's) - decrease in Ca2+ in urine
68
what causes Gitelman's syndrome?
Loss of function mutation:
- NCC can no longer transport Na+ and Cl- into distal tubule, so there is more NaCl in the urine
- less NaCl reabsorption means less water reabsorption, causing polyuria
still unknown as to why hypocalciuria is caused
69
how can functions of transporters in mice be observed?
xenopus oocyte studies:
- inject RNA of a protein of interest
- protein of interest is made and used at the membrane
- functional analysis of NCC: radioactive Na+ is tracked to see how much radioactivity is in the ICF and thus how much Na+ transport into the distal tubule
70
what are thiazide diuretics?
Chlorothiazide:
- inhibit NCC to reduce NaCl reabsorption
- reduces water reabsorption to increase urine flow and remove excess ECF volume
- treats high BP as cardiac output falls due to the lowered ECF volume
- Gitelman's-like side effects
71
what is the benefit of carrying one mutation for ROMK, NCC or NKCC2?
protects against hypertension
72
what are the roles of the late distal tubule, collecting tubules and cortical collecting duct?
- concentrates urine
- reabsorption of Na+ and water
- secretion of K+ and H+ into urine
connecting tubules link late DT to CCD
73
what are the two cell types of the late distal tubule and the cortical collecting duct?
Principal:
- Na+ and water reabsorption
- K+ and H+ secretion
Intercalated:
- alpha-intercalated cell
- beta-intercalated cell
- H+ secretion and reabsorption
- bicarbonate secretion and reabsorption
74
what is transported at the basolateral membrane of the principal cell of the late DT and CCD?
1. sodium-potassium ATPase
- sets up electrochemical driving force of Na+ by keeping intracellular Na+ concentration low
2. Aquaporins 3 and 4
- water is reabsorbed to peritubular capillary
- always open and active
3. Kir2.3: K+ channel
- allows K+ reabsorption into the peritubular capillary
75
what is transported at the apical membrane of the principal cell of the late DT and CCD?
1. ENaC: Na+ selective channel
- allows Na+ to diffuse into cell down the electrochemical gradient
- Na+ is then lost on the basolateral membrane by ATPase, so net reabsorption
- water is also reabsorbed by AQP3 and AQP4
- regulation of ENaC determines the final Na+ conc in urine
2. aquaporin 2
- water moves down osmotic gradient across the apical membrane
3. ROMK:
- drives potassium secretion across the apical membrane into the tubular fluid and so into urine
76
what is the relationship between Na+ and H+ in the principal cells of the late DT and CCD?
- the more Na+ that is reabsorbed, the more H+ that is secreted into the urine
- can cause metabolic alkalosis in Bartter's and Gitelman's
77
what is the relationship between Na+ and K+ in the principal cells of the late DT and CCD?
- there is an enhanced driving force for Na+ at the principal cell, so more reabsorption by ENaC
- this causes more secretion of K+
- in Bartter's and Gitelman's syndromes, this process is amplified
- this causes a major fall in plasma K+ levels due to loss of urine
78
what are the 3 principal cell diseases?
1. Diabetes insipidus: AQP2
- problem with AQP2 mechanism, so there is a struggle to reabsorb water
- major loss of fluid in the urine
2. Liddle's syndrome: ENaC
- functional mutation in ENaC subunit
- causes absorption of too much water which increases ECF volume
- causes hypertension
3. pseudohypoaldosteronism
79
what is amiloride?
diuretic used to treat high BP:
- an antagonist of ENaC: blocks Na+ reabsorption across the apical membrane
- this causes a loss in the osmotic gradient so less water reabsorption
- more Na+ and water is lost in the urine
- this causes decreased ECF volume and so reduces hypertension
80
what is the role of the alpha-intercalated cells in the late DT and CCD?
1. H+ secretion
| 2. bicarbonate reabsorption
81
what is transported at the basolateral membrane of the alpha-intercalated cell of the late DT and CCD?
1. chloride channel
- Cl- is reabsorbed/recycled and sets up electrochemical gradient to be exchanged for bicarbonate by AE1
2. AE1: bicarbonate-chloride exchanger
- bicarbonate is made inside the cell and is exchanged out of the cell, with Cl- entering the cell
- bicarbonate is reabsorbed into peritubular capillary
82
what is transported at the apical membrane of the principal cell of the late DT and CCD?
1. Proton ATPase:
- hydrolyses ATP to pump H+ against its conc gradient into tubular fluid
- causes loss of H+ to urine
- secretion
83
what is the role of the beta-intercalated cells in the late DT and CCD?
1. bicarbonate secretion
2. H+ and Cl- absorption
(opposite of alpha ICs)
84
what is transported at the basolateral membrane of the beta-intercalated cell of the late DT and CCD?
1. proton ATPase
| - protons are reabsorbed
85
what is transported at the apical membrane of the beta-intercalated cell of the late DT and CCD?
1. chloride channel
- secretes Cl-
2. AE1:
- exchanges chloride for bicarbonate
- chloride is absorbed into cell
- bicarbonate is secreted into tubular fluid and into the urine
86
what is the relationship between alpha and beta IC cells?
- they are dynamic so can change formation depending on the function required
87
what are the properties of the medullary collecting duct?
- low Na+ permeability due to less ENaC
| - high H2O and urea permeability in the presence of vasopressin due to trafficking of aquaporins
88
what is acute renal failure and its symptoms?
fall in GFR over hours/days
symptoms:
- hypovolaemia: oligura (low urine flow) due to low GFR and expansion of ECF volume
- hyperkalaemia: lack of K+ secretion so increased plasma K+ -> affects cardiac excitability
- acidosis: depression of CNS as more H+ accumulation due to low urine flow
- high urea/creatinine: cannot remove nitrogenous waste
- impaired mental functon
- nausea and vomiting
89
what causes acute renal failure and how can it be treated?
Causes:
- impaired fluid and electrolyte homeostasis
- accumulation of nitrogenous waste due to inability to excrete
lasts 1 week and is reversible
treatment: short term dialysis until kidneys gain function again
90
what does the oligura of acute renal failure cause?
- hypotension due to loss of blood volume, causes poor renal perfusion of blood
- rhabdomyolysis (release of myoglobin from damaged muscle) has toxic effects on kidney tubules
- compression damage causes release of ICF to ECF, so K+ enters ECF
- tachycardia due to increased plasma K+ which had been released from damaged cells
- low bicarbonate -> acidosis
91
how is oliguria treated?
- IV saline – treat hyperkalaemia and get blood volume and pressure back to normal for normal perfusion of kidneys for glomerular filtration
- HCO3- - to bring level to normal
- Rehydrate in this case – increase blood volume
- Dialysis if oliguria persists
