What are the two types of nephron?
Describe blood flow in the glomerulus
80% leaves via efferent arteriole
Same in both nephron types
In general, what can pass through the glomerular filter and what cant?
Small molecules (Small molecular weight and radius of <1.48nm)
Compare ultrafiltrate in the Bowman's capsule to plasma
Idnetical to plasma without the large proteins and cells
What are the 3 layers of the glomerular filtration barrier
Give a brief outline of each's form and function
Permeable to water, salts and glucose
Filtrate moves between cells
Acellular, gelatinous, collagen and glycoproteins
Permeable to small proteins
negative glycoproteins repel protein movement
Pseudopodia interdigitate to form filtration slits
What is the effect of charge on glomerular filtration?
What's the clinical relevance?
Negative charge of the basement membrane glycoproteins repels movement of proteins across barrier
If this negative charge is lost (ie. disease process occurs) then the proteins are more readily filtered
This is Proteinurea
Outline the forces behind flitration (include numbers)
Give the normal filtration pressure
Hydrostatic pressure in the capillary:
Hydrostatic pressure in tubule/capsule:
Osmotic pressure in glomerulus:
10mmHG net filtration pressure
Describe the functions of myogenic autoregulation in the renal corpuscle
Keeps GFR within limits:
Increase in blood flow leads to afferent arteriole constriction to maintain filtration pressure and hence GFR
Decrease in blood pressure leads to afferent arteriole dilation or efferent arteriole constriction to maintain filtration pressure and hence GFR
Outline the control of myogenic autoregulation
Changes in tubular flow rate as a result of GFR changes leads to change in amount of NaCl which reaches the distal tubule
E.g. Inc. BP = Inc. Glomerular capillary pressure = Inc. GFR
Macula densa cells in the DCT respond to changes in luminal [Na+] and [Cl-] and trigger autoregulation to correct GFR
Only applies in acute changes, long-standing change not regulated this way
Where is the macula densa found?
Close to the Renal corpuscle
Describe the mechanism by which macula densa cells detect NaCl changes in lumen and respond
Concentration dependent salt intake via NaK2Cl cotransporter in apical membrane of macula densa cells
Stimulates juxtaglomerular apparatus to release chemicals which affect afferent arteriolar tone:
Adenosine - Vasoconstriction
Prostaglandins - Vasodilation
Give the response of the macula densa should NaCl conc rise or fall in DCT
GFR must fall
Therefore Adenosine released to vasoconstrict AA
GFR must rise
Therefore prostaglandins released to vasodilate AA
What is tubular reabsorption?
Solutes and water are removed from the tubular fluid and transported back to blood
Called reabsorption because the substances have already been absorbed into the blood somewhere else
Outline reabsorption in the PCT
Driven by Na+ uptake
Other ions accompany to maintain electro-neutrality (Cl- and HCO3-)
Solutes moved from lumen to interstitium to capillaries
Transcellular or paracellular
Give the proportions of solutes reabsorbed for common solutes in the PCT (oh, and include water)
100% of nutrient (Glucose)
Outline the tubular reabsorption of Na+ and water in the PCT
Na+ pumped out of cells on basolateral membrane by Na+/K+ ATPase
Na+ moves across apical membrane down conc gradient
Na+ channel or membrane transporter utilised
Common transporters in PCT are Na+/H+ antiporter and Na+/Glucose symporter
Water moves down osmotic gradient created
What are the types of channels and transporters involved in Na+ reabsorption outside of the PCT (but within the nephron, as context might imply)
Loop of Henle:
Late DT and CD:
Describe the reabsorption of Glucose
How does the mechanism of this allow for dysfunction?
SGLUT co-transporters in PCT
Transport 2Na+ ions with 1 Glucose into cell
Glucose moves out of basolateral membrane of cell via facilitated diffusion into peritubular capillaries
100% normally reabsorbed
Transport maximum (finite number of transporters have maximum rate)
Tm = 200mg/100ml
If exceed the rest of glucose spills into urine
Outline secretion in the nephron and the common substances secreted
Involves transepithelial transport
Second route for solutes into lumen (useful considering only 20 of blood filtered)
Organic anions and cations
Outline organic cation secretion
Na+/K+ ATPase creates favourable electrical and concentration gradient
Passive carrier mediated transport of Organic cations (OC+) into cell (uniport)
Na+/H+ antiporter creates H+ gradient on apical membrane (H+ efflux)
H+/OC+ exchanger allows secretion of OC+ into lumen
OC+ subject to transport maximums like any transporter mediated secretion/absorption process
Give some examples of Endogenous organic products that are secreted and drugs that are secreted
What are the normal GFRs for men and women?
Why is GFR clinically important?
Gives an indication as to how well the kidney works
What measurements should we be able to calculate for a renal patient?
Filtered load (Applied to Tm)
Describe how Renal plasma flow is calculated
Input into renal artery per unit time (usually 1.1L/min)
All blood flows through glomeruli in the cortex
Haemocrit/Erythrocyte volume fraction is percentage of blood that is RBCs
Renal plasma flow x (100 - Haemocrit) = RPF (605ml/min)
What is filtration fraction?
How is filtration fraction calculated?
Give normal values
Proportion of substance actually filtered
605ml of plasma enters glomeruli every minute
20% is filtered (filtration fraction)
125ml/min is filtered
480ml/min passes to peritubular capillaries
GFR / RPF = filtration fraction
What is renal clearance?
Give an example
"The volume of plasma from which any substance is completely removed by the kidney in a given amount of time"
E.g. Clearance of urea = 65ml/min
i.e. Kidney removes all urea from 65ml of plasma per minute
How is renal clearance rate related to GFR?
In a substance that is completely filtered at the glomerulus and is not reabsorped at all, the renal clearance (amount of plasma cleared) is equal to the amount of plasma filtered (GFR)
What compounds can we use to calculate GFR?
Give the equation for calculating renal clearance of a perfectly filtered non-reabsorbed substance and hence GFR
Clearance rate/GFR (ml/min)
( Urine conc of substance x Urine flow rate (ml/min) )
Plasma conc of substance
Yeah, it's ugly, once again sorry about the equations!
What is 'Filtered load'?
Calculate the Filtered load of glucose, show your working!
The amount of each substance filtered per unit volume of filtrate
GFR of a substance x Plasma conc of a substance
GFR = 125ml/min
Plasma conc = 200mg/ml OR 2mg/ml
125ml/min x 2mg/ml = 250mg/min
Define renal threshold
The plasma concentration of a substance at ehich the transport maximum of a substance is reached and the substance starts spilling into urine
What is Transport maximum?
The maximum rate of removal of a substance from the urinary filtrate
Units are Mg/ml
Filtered load - Tm = Substance lost per minute
Give some examples of disease/physiological causes of glycosuria
Following a carbohydrate rich meal
In new borns due to un developed reanl system
Chronic renal failure
Genetic defects leading to reduced symporters in kidney lumen
Describe how glycosuria affects the filtrate
PCT cannot filter all glucose
So at the end of the PCT an increased amount of filtrate is present in the urine
This is due to the increased number of solutes, therefore more water is retained to maintain isosmotic filtrate
Where in the kidney tubule are amino acids reabsorbed?
What are the two types of aminoaciduria?
Describe overflow aminoaciduria
General and specific overflow
Increased excretion of all amino acids
Increased secretion of specific amino acid(s)
Describe renal aminoaciduria
What other clinical condition may arise?
Mainly confined to dibasic acids
Genetic cause (Lack of transport proteins)
Impaired reabsorption of cysteine (an abnormally insoluble amino acid) is associated with renal stone formation