Session 3 Flashcards
What creates the hydrostatic pressure in the glomerulus?
Diameter of afferent arteriole > diameter of efferent arteriole
Describe how to calculate renal plasma flow
(1-erythrocye volume fraction) * renal blood flow
0.45 * 1100 = 605ml/min plasma
Describe how to calculate the filtration fraction
GFR/RPF *100
~125/605 = 20%
Describe the differences between a cortical and a juxtamedullary nephron
Cortical (90%) - outer part of cortex, small glomerulus, short LoH next to the outer cortex, diameter of AA>EA, EA forms peritubular capillaries, high conc. renin
Juxtamedullary (10%) - inner part of cortex, large glomerulus, long LoH, diameter of AA=EA, EA forms vasa recta, low conc. renin
What change in the glomerulus basement membrane can lead to proteinuria?
Loss of negative charge - filter not as selective and more proteins filtered
Describe how to calculate the net filtration pressure
Hydrostatic pressure of capillary - hydrostatic pressure in Bowman’s capsule - oncotic pressure difference between tubule lumen and capillary
~ 50-15-25=10mmHg
Describe the myogenic response to maintain GFR after changes in blood pressure
Increased BP -> increased afferent resistance -> decreased hydrostatic pressure of capillary
Decreased BP -> decreased afferent resistance/increased efferent resistance -> increased hydrostatic pressure of capillary
Describe the regulation of capillary hydrostatic pressure by tubular glomerular feedback
Changes in tubular flow rate as a result of changes in GFR change the amount of NaCl in the distal tubule, which is detected by macula densa cells. These cells regulate arterial tone and hence filtration rate by stimulating the juxtaglomerular apparatus to release chemicals.
Describe what chemicals are released by the juxtaglomerular apparatus to maintain GFR after changes in blood pressure
Increased NaCl -> MD cells release adenosine -> vasodilation of EA -> decreased GFR
Decreased NaCl -> MD cells release prostaglandins -> vasodilation of AA -> increased GFR
What are the different apical sodium channels in different parts of the tubule?
PCT: Na/H antiporter, Na-glucose symporter and Na-AA cotransporter
LoH: Na-K-2Cl symporter
Early DCT: Na-Cl symporter
Late DCT and CD: ENaC
Under what circumstances will glucose leave in the urine?
If the concentration in plasma exceeds the transport maximum. Leads to polyuria.
Describe the proportion of different substances that are normally absorbed by the end of the PCT
100% nutrients, 65% water, 80-90% HCO3, 65% Cl, 67% Na, 65% K.
What substances are secreted into the tubule and why is this useful?
H+, K+, ammonium, creatinine and urea. Useful because only 20% of plasma is filtered each time blood passes through the kidney.
Describe how organic actions are secreted
They enter the basolateral membrane in the PCT down favourable electrical (Na/K pump) and chemical gradients.
Secretion into lumen by a H/OC exchanger driven by H+ gradient set up by Na/H antiporter.
What substances are used the estimate GFT and why?
Creatinine and inulin (more precise but expensive) because they are freely filtered and not altered as they travel through the nephron (not secreted, reabsorbed, metabolised).
How is eGFR calculated?
Using a formula that uses serum concentration of creatinine and patients weight to predict creatinine clearance.
How is GFR calculated?
Renal clearance rate = (conc. of substance in urine * urine flow rate) / plasma conc. of substance
RC=(UV)/P
Derived from: filtration rate = RCP=V*U
What is renal clearance?
The volume of plasma from which substance X can be completely cleared to urine per unit time (reality is larger volume of plasma partially cleared per unit time)
Give the normal GFR values for males and females
Males: 90-130ml/min
Females: 80-120ml/min
What is the problem with calculating GFR using creatinine?
Leads to an overestimation because some creatinine is secreted in the tubule. More significant with lower GFR in disease.
How is the filtered load of a substance calculated?
Plasma concentration * GFR (calculated using creatinine)
How is the amount of a substance excreted calculated?
Urine concentration * urine flow rate
How is the fractional tubular reabsorption calculated?
100 - fractional excretion
List the molecular factors that affect the movement between plasma and tubules
More lipophilic -> more diffusion into plasma from tubule
More hydrophilic(electrical charge) -> less diffusion into plasma
More binding to plasma proteins -> less excretion
More binding to tissue proteins -> less availability for renal clearance
What is the fractional excretion?
The percentage of a filtered solute that remains unreabsorbed by the nephron.
Solute excreted in urine/filtered load
How is the apparent volume of distribution measured and what is it useful for?
By measuring plasma concentration of drug. Tells you how drug distributes throughout the body.
High vol = lipophillic, leaves plasma(less kidney excretion)
Low vol = charged and confined to plasma
How does phase 1 and 2 metabolism in the liver increase kidney excretion?
Increases its charge, reducing lipophilicity so the drug does not diffuse out of the tubular lumen as easily.
Describe the excretion of weak acidic anions in acidic/alkaline urine
Acidic - more likely to become protonated and neutral. More lipophilic so more diffuses into plasma from tubule.
Alkaline - more excreted
Describe the excretion of weak basic cations in acidic/alkaline urine
Alkaline - more likely to become deprotonated and neutral. More lipophilic so more diffuses into plasma from tubule.
Acidic - more excreted
Describe some disease states that affect renal clearance
Heart disease - decreased GFR reduces renal clearance
Hepatic disease - less 1/2 metabolism reduces renal clearance
Cirrhosis/hepatitis - less albumin which increases free plasma concentration of the drug and increases renal clearance
How is the rate of creatinine secretion calculated?
Calculate the difference between: Excreted creatinine (U * V) Filtered creatinine (GFR calculated from inulin * P)
