lecture 9 (renal) Flashcards
(48 cards)
1
Q
what factors control glomerular filtration rate?
A
- blood flow through glomerulus
- surface area of nephrons
- colloid osmotic pressure in bowman space
- difference in hydrostatic pressure
2
Q
how can you measure single nephron GFR?
A
- plugging blood capillary
- inject inulin
- watch merge rom glomerulus and enter tubular fluid
- amount of inulin filtered = amount collected
3
Q
how do you calculate single nephron GFR?
A
- (TF insulin x collection rate)/ P insulin
4
Q
what 4 variables control GFR?
A
- permeably coefficient
- hydrostatic pressure difference
- colloid osmotic pressure difference
- rate of blood flow through glomerulus
5
Q
what is Pcap ?
A
- capillary osmotic pressure
(drives fluid out capillary)
6
Q
what do changes in Kf cause?
A
- decrease in GFR
- decreased SA for permeability
7
Q
what could this decrease in GFR be a result of?
A
- renal failure (fewer nephrons)
- diabetic nephropathy
- nephrotic syndrome
- nephritic syndrome
8
Q
what is nephrotic syndrome?
A
- kidney disease
- characterised by oedema and loss of protein from plasma into urine
9
Q
what is nephritic syndrome?
A
- presents as hematuria (blood in urine)
- elevated blood pressure
- decreased urine output
- edema
- large holes present in glomerular filtration barrier as collagen breakdown
10
Q
what does atrial natriuretic peptide do?
A
- decrease efferent and afferent resistances
- can control flow through nephron
11
Q
how does pressure change with a higher flow?
A
- colloid osmotic pressure increases
- hydrostatic and osmotic pressure decrease
12
Q
what happens to protein concentration in normal flow?
A
- increases as volume decreases in each bolus
13
Q
what happens to protein concentration in fast flow?
A
- increases less and less H2O is removed from each bolus due to shorter time in glomerulus
14
Q
what does a change in hydrostatic pressure in capillary cause?
A
- volume increases
- hypertension
- increase in GFR
15
Q
what does a change in hydrostatic pressure in bowman space cause?
A
- renal stones
- kinks in ureter
- blockage
- decrease in GFR
16
Q
how is net hydrostatic pressure calculated?
A
- P capillary - P bowman space
17
Q
how do changes in colloid osmotic pressure affect capillary?
A
- increases volume
- decreases protein conc
- increase in GFR
18
Q
how do changes in colloid osmotic pressure affect bowman space?
A
- proteinuria
- increase in GFR
19
Q
how is net colloid osmotic pressure calculated?
A
pi capillary - pi bowmans space
20
Q
what are the toxic effects of chemicals on the nephron?
A
- reasons for susceptibility of nephron to toxic insult
- mechanism of drug and secretion and reabsorption
- specific effects of chemicals and drugs on proximal tubule and consequent clinical effects
21
Q
what happens in acute kidney disease?
A
- kidneys stop working properly
- can be drug induced
- associated with high rates of mortality
22
Q
what are causative diseases to acute kidney disease?
A
- diabetes mellitus
- poly-pharmacy
23
Q
what factors contribute towards acute kidney disease?
A
- changes in haemodynamics
- damage to glomerulus
- tubular cell damage
- inflammation
24
Q
why is the nephron so susceptible to toxic insult?
A
- highly perfused tissues
- exposed to circulating toxins
25
what problems occur with toxins in the proximal tubule?
- water is absorbed, if carrying toxins can effect
- sodium/water toxicity
26
what is the pars convoluta?
- 'bendy' bit
- where water and sodium is absorbed
27
what is the proximal tubule a primary target for?
- nephrotoxicity
28
why is only 70% of water reabsorbed?
- solutes are pumped out
- solute is trapped in lateral interspace between proximal tubule cells
29
what does the tubular loop contain?
- any solutes that have been excreted or diffused out
30
where do the tubular capillaries go?
- into the systemic circulation
31
what occurs in diabetes?
- more glucose remains in the tubule
- causes more water loss
32
why is the proximal tubule a target?
- removal fo 70% of water from tubular fluid generates a concentrated solution to which proximal tubule cells are exposed
33
are transporters specific or non specific?
- non specific
- so often misidentify
34
where may metabolites intended for excretion be reabsorbed?
- from tubular fluid in PCT
35
where may drugs secreted from blood become trapped?
- in PCT cells
36
what is cisplatin ?
- anti cancer drug
37
why isn't cisplatin a good substrate for the reflux transporters?
- nephrotoxic
- efficient taken up into proximal tubule
- rate of secretion lower
- can cause poisoning of kidneys
38
what is required alongside cisplatin?
- uptake blocker
39
what does the uptake blocker do?
- outcompetes cisplatin
- excreted into PCT
- refluxed into urine
- stops PCT cells absorbing as much cisplatin
40
what occurs with high exposure of cisplatin?
- destruction of mitochondria
- proximal tubular cell death
- organic solutes lost to urine
- Na loss increased
- H2O loss increased
41
what does high exposure to cisplatin cause?
- fanconi syndrome
42
what are cephalosporins?
- beta lactam antimicrobials used to mamange infections
- generally not nephrotoxic
- active uptake from systemic circulation
- good substrate for MDR1 and MDR4 efflux pumps
43
what is cephaloridin?
- derivative of an antibiotic
- selective toxicity to proximal tubule cells
- absorbed from systemic circulation by cation/anion transporter on basolateral membrane
44
what is cephaloridine taken up by?
- OAT1 at basolateral membrane
45
what drug-drug interactions occur in PCT?
- efflux into urine
46
what is an example of a nephrotoxic drug?
- tenofovir
- anti-viral
- mitochondrial toxin
47
how does tenofivir work?
- pumped into PCT cells well by organic ion transporter
- reasonably substrate
- accumulates with prolonged usage
48
what are the endogenous substrates?
-
