Flow, GFR And Pharmacology Flashcards
What is the average renal blood flow?
1.1 L/min
What is the renal plasma flow?
Renal blood flow minus the haematocrit (erythrocyte volume fraction - usually 45%)
RPF = 0.55 x RBF
Generally, how many segmental arteries are there per kidney?
5
What are the 2 types of nephron?
Cortical
Juxtamedullary
Give some features of cortical nephrons
Small glomerulus
Afferent arteriole has large diameter than efferent
Sympathetic rich
High concentration of renin
Give some features of the juxtamedullary nephrons
Big glomerulus
Diameter of afferent close to diameter of efferent
Sympathetic poor
Almost no concentration of renin
How much of the blood from a renal artery is filtered at any one time?
20%
What are the 3 layers of the glomerular filter?
Capillary endothelium
Basement membrane
Podocyte layer
Which molecule do we think is the biggest molecule that can pass through glomerular filtration?
Inulin
Which charge is repelled more at the glomerulus?
Negative charges
What are the 3 forces acting at the filter?
Hydrostatic pressure in capillary
Hydrostatic pressure in Bowman’s capsule
Oncotic pressure in capillary
What is the myogenic response?
The control over GFR by changing the tone of the arteriole walls
Controls GFR through day-to-day BP changes
Describe the effect on the GFR of an increase in tone in the afferent arteriole
Increased resistance leads to reduced blood flow
Decreased hydrostatic pressure
Decreased GFR
Why doesn’t the flow rate change?
Because change is resistance is proportional to change in pressure
Which organs have the best autoregulation?
Heart
Brain
Kidneys
What is the role of autoregulation?
To keep GFR within the normal ranges
Describe tubular-glomerular feedback
Changes in tubular flow rate occur as a result of changes in GFR
This changes the amount of NaCl that reaches the DCT
Cl- ions detected in the macula densa
Stimulates juxtaglomerular apparatus to release appropriate chemicals
What chemicals can be released by the JGA and what are their effects?
Adenosine - vasodilator of the efferent arteriole - reduces GFR
Prostaglandins - vasodilator of afferent arteriole - increases GFR
Describe glucose cotransport in the PCT
Via SGLUT
2 Na+ ions plus 1 glucose molecule
Secondary active transport
What substances do we secrete into the kidney tubules?
Protons (H+)
Potassium
Organic anions and cations (a lot of the drugs that we prescribe)
Give examples of endogenous cations
ACH Dopamine Adrenaline Histamine Serotonin
Give examples of drugs that are cations
Sulfonamides
Morphine
Atropine
Give examples of endogenous anions
Urate
Bile salts
Fatty acids
Give examples of drugs that are anions
Penicillin
Salicylate
NSAIDs
What is the normal GFR range for males and females?
Males = 115 - 125 ml/min Females = 90 - 100
What is the formula for renal clearance?
RC = UV/P
U = urinary conc of substance V = flow rate of urine formation P = plasma conc of same substance
What factors does the complicated eGFR equation take into account?
Age
Sex
Mass
Ethnicity
What does xenobiotic mean?
Not belonging in the body
What processes contribute to pharmacokinetics?
Absorption
Distribution
Metabolism
Excretion
What is drug clearance?
The rate of elimination by the kidney and the liver
How do we work out the half-life of a drug?
(0.693 x Vd) / CL
0.693 - constant
Vd - volume of distribution
CL - clearance rate of drug
Generally the rate of removal of a drug is proportional to…
The drug’s free concentration in the plasma
Linear properties
If a drug is more lipophilic how does this affect its excretion?
Can diffuse more easily back out of the kidney tubule
Across the plasma membrane
How does plasma protein binding affect drug excretion?
Reduces the amount of drug available for glomerular filtration
(And/or removal by the anion/cation transporters in the tubules)
If the drug has a high volume of distribution then the drug is more likely to be …
Lipophilic
Does a large volume of distribution increase or decrease the half life?
Increase
Describe the 2 phases of liver metabolism
Phase I = reduction, oxidation, hydroxylation
Phase II = conjugation
(Both phases act to increase charge to make kidney excretion easier)
What occurs when weak acidic anions are present in acidic urine?
Will be protonated
Become electrically neutral
Diffuse out of the nephron
What happens when weak acidic anions are in more alkaline urine?
Less likely to be protonated
More will be excreted (as will be charged therefore less likely to be reabsorbed)
What happens when weak bases are in acidic urine?
Will become protonated
Less lipophilic
More drug excreted
What happens when weak bases are in more alkaline urine?
More likely to be electrically neutral
More lipophilic
Can diffuse out of nephron
Less excreted
Define renal clearance
The virtual volume of plasma that would be totally cleared of a given solute per unit time.
Describe the features of inulin that make it good for measuring GFR
Inert Only filtered (not secreted or reabsorbed)
What molecules can be used to estimate GFR?
Creatinine
Inulin
What are the downsides of using inulin?
Expensive
Has to be injected
