Flashcards in Session 3 - Filtration Deck (95):
Outline the sequence of arteries leading into the kidney
• Renal Artery -> Segmental Arteries -> Interlobar Arteries -> Arcuate Arteries -> Interlobular Arteries -> Afferent Arterioles
Give one way in which the structure of the renal arteries increases pressure in the glomerulus
• The diameter of each afferent arteriole is slightly greater than the diameter of the associated efferent arteriole
What is the size limit and effective molecular radius for filtration?
• Size limit - 5,200
• Effective molecular radius - 1.48 nm
Why are proteins not usually filtered into the kidney?
• Basement membrane and podocyte glycocalyx have many negatively charged glycoproteins which repel protein movement
How much blood is filtered by the renal artery at any one time?
What happens to blood not filtered by the glomerulus?
• Exits via efferent arteriole
What are the two types of kidney nephron?
Why is a juxtamedullary nephron named thus?
• Glomeruli located in cortex, but next to medullary bounds
Give two differences between cortical and juxtamedullary nephrons
• Juxtamedullary has longer loops of henle
• Arrangement of peritubular capillaries around cortical nephrons messy
• Structured and organised arrangement of capillaries in juxtamedullary nephron
• Countercurrent flow in organised juxtamedullary nephron
How is filtration a selective process?
• Cells and large proteins do not get filtered through
• Water, salts and small molecules pass through
• Thanks to filtration mesh provided by podocytes
Where do the glomerula tufts always lie?
• In the cortex
Where does blood to be filtered arrive in the kidney?
• Glomerula tuft
What are the three layers in the filtration barrier?
• Capillary endothelium
○ Water, salts, glucose
• Basement membrane
○ Acellular gelatinous layer of collagen/glycoprotein
○ Permeable to small proteins
○ -'ve charge to repel protein movement
• Podocyte layer
○ Pseudopods interdigitate and form filtration slits
It is more difficult for a positive protein to pass through membrane than a negative. Do you agree?
• No, negative repelled by -vely charged basement membrane
What happens if a clinical conditions results in negative proteins being stripped of their charge?
• They will be filtered and appear in the urine
Give conc of following in plasma and ultrafiltrate
• Glucose 100
• Na+ mmol/l 140
• Urea mg/dl 15
• Creatinine umol/l 60-120
Give three physical forces involved in plasma filtration
• Hydrostatic pressure in the capillary (regulated) (capillary -> tubule)
• Hydrostatic pressure in bowman's capsule (tubule -> capillary)
• Osmotic (oncotic) pressure differences between the capillary and tubular (tubular -> Capillary)
What is the net filtration pressure in the glomerulosa?
What is the average hydrostatic pressure between capillaries and tubule?
• 50mmHG (about half of normal pressure)
What is the effect of charge on filtration?
• Neutral molecule - The bigger it is, the less likely to get through
• Anions - Negative charge also repels, more difficult to get through
• Cations - Positive charge allows slightly bigger molecules through
How is blood in afferent arteriole (going out) different to efferent (going in)?
• Oncotic (protein) pressure higher
• Blood is more concentrated
Give one cause of proteinuria involving filtration forces
• In many disease processes the negative charge is lost on the filtration barrier, so proteins are more readily filtered
What is osmotic pressure?
• Force generated because of solute within solvent
What is oncotic pressure?
• Oncotic force in generated because of protein within solute
Why is absorption in kidney called reabsorption?
• Already been absorbed once by GI tract
Give three mechanisms by which reabsorption occurs
• Active transport
What is tubular secretion?
• Substances secreted into renal tubular lumen from peritubular capillaries
By what mechanism are substances secreted into the tubular lumen?
• Active transport
What two main types of substances are secreted into the tubular lumen?
• Those present in great excess
• Natural poisons
What does secretion help to maintain?
• Blood pH
Give three examples of things actively secreted
What are two methods of secretion into the PCT?
• Entry by passive carrier
• Secretion into the lumen
What is entry by passive carrier?
• Diffusion across basolateral membrane down conc grad created by Na+/K+ ATPase
How does entry by active secretion differ to passive?
• Directly uses ATM and H+ gradient creat by Na+-H+ antiporter
Give two forms of reabsorption?
How easy is it for a cation to get through the filter compared to an anion?
• Positive charge of cation allows slighty bigger molecules through than anions
What is reabsorption in PCT driven by?
• Sodium uptake
How is Na+ reabsorbed in tubular cells
• 3Na-2K-ATPase (Na into ECF, K+ into cell)
• Na+ moves across the apical membrane from tubule lumen down its concentration gradient
• Water follows into cell
In what way do solutes move in the PCT?
• Tubular lumen -> Intersticium -> Capillaries
What are the three mechanisms via which tubular reabsorption occurs?
• Active transport
What does iso-osmotic mean when applied to reabsorption?
• Osmosis does not take effect
Where does unregulated absorption occur?
• Proximal convoluted tubule
What is the method via which reabsorption occurs?
• Co-transport, following active transport
What is the transport maximum?
• If plasma conc exceeds Tm, the rest spills over into urine
What is the reabsorption path?
• Lumen -> Intersticium -> Peritubular capillaries
How is reabsorption different from glomerula filtration?
• Occurs primarily through cells
What 7 main substances are secreted into glomerula filtrate?
• Ammonium ions
• Some hormones
• Some drugs
Why do we need kidney secretion?
• Only 20% of plasma filtered in renal corpuscle each time
From where does tubular secretion occur?
• From the epithelial cells that line the renal tubules and collecting duct into the glomerular filtrate
How are organic cations secreted?
1) Entry by passive carrier into tubular lumen cell
a. Positive cation from ECF moves into negative cell down electrical gradient. This is as a result of basolateral 3 Na+/2 K+ ATPase
2) Secretion into the lumen
a. H-OC exchanger driven by H+ gradient created by the Na+-H+ antiporter
b. Na+ into cell from lumen, H+ out cell into lumen
c. Drives H+ into cell from lumen by creating conc grad
d. Organic Cation out by active transporter
Name three endogenous cations
Name three cationic drugs
Name three endogenous anions
• Bile salts
• Fatty acids
Name two anionic drugs
What is secondary active transport?
• Na+/K+ ATPase used to generate Na+ gradient
Where is glucose reabsorbed in the nephron?
• Proximal convoluted tubule
Through what transporter is glucose reabsorbed in the proximal convoluted tubule?
What is SGLUT?
• 2 Na+ ions and 1 glucose
• Glucose travels from lumen of tubule to the peritubular capillaries (moves into peritubular capillaries by facillitated diffussion
What is Tm?
• Transport maximum from tubule to capillaries
What is the renal threshold for glucose?
What occurs if transport maximum for glucose exceeded?
• Rest of glucose spills over into urine
• Causes polyuria
Where does reabsorption of amino acids occur?
• Proximal convoluted tubule via Na+ co-transporters
What is clearance?
• The volume of plasma from which any substance is completely removed by the kidney in a given amount of time (usually 1 minute)
What is the clearance calculation?
• Clearance rate = Urine concentration of substance x Urine flow rate / Plasma concentration of the substance
What is excretion rate?
• Amount in urine x Urine flow rate
When are the inputs and outputs of the kidney?
• One input - Renal artery
• Two outputs - Renal vein and Ureter
What can we measure from the rate at which a substance appears in the urine, provided that that substance is completely cleared
• The GFR
What is the Tm for glucose in males and females?
• Males - 375mg/min
• Female 300 mg/min females
What is glomerular filtration rate?
• The volume of plasma from which any substance (X) is completely removed by the kidney in a given amount of time
What is GFR a measure of?
• Kidneys ability to filter a substance (overall function)
What does a fall in GFR indicate?
• Kidney disease is progressing
In order to measure GFR, what properties must a substance have?
• Must be freely filtered across the glomerulus
• Must not be reabsorbed, secreted or metabolised
• Must pass directly into the urine
What is standard renal blood flow?
How can we find out renal plasma flow?
• Heamatocrit is the volume (%) of RBC in blood
• Normally 45%
• 0.55 x 1.1 (RBF) = 605ml - Plasma flow
What is the filtration fraction of 605 ml plasma?
• 605ml x 0.2 = 125ml (20% blood processed per minute)
What is GFR for males?
• 115-125 ml/min
What is GFR in females?
• 90/100 mi/min
Outline the GFR of inulin, glucose and para-aminohippurate
Inulin - 125ml/min - Not reabsorbed, not secreted
Glucose - 0 - Completely reabsorbed
Para-aminohippurate - 625 ml/min (Secreted!)
Outline use of urea
• Used as an active osmol by the kidney
What is filtration fraction?
• Proportion of a substance actually filtered
• If renal plasma flow is 605ml/min, 20% of all plasma is filtered, 125ml filtered through into bowman's space and 480ml passes through into peritubular capillaries
• Filtration fraction = Glomerular filtration rate/Renal plasma flow
• Filtration fraction about 20%
What is autoregulation?
• Auto-regulatory mechanisms keep GFR within normal limits when arterial BP within physiological limits (80-120 average BP)
What is myogenic autoregulation?
• Smooth muscles of afferent capillaries of glomerulus (those going in) contract to increase or decrease pressure
What are the limits of myogenic autoregulation?
• Normal average blood pressure between 80-120 mmHG
What is GFR?
• Glomerular filtration rate
• A measure of the kidney's ability to filter a substance
Give two mechanisms of controlling blood flow to glomerulosa
• Smooth muscle control in afferent and efferent arterioles
• Tubular Glomerular feedback
What happens to smooth muscle in afferent arterioles to glomerulosa if blood pressure drops?
What happens to smooth muscle in afferent arterioles to glomerulosa if blood pressure increases
Outline tubular glomeruola feedback
• If arterial pressure too high
• Increases glomerular capillary pressure
• Increased glomerula filtration rate
• More Na+ and Cl- in distal convoluted tubule
• Macula densa cell in the JGA respond
How do the macula densa cells in the JGA oppose high GFR
• Release adenosine (vasoconstrictor) or prostaglandin (Vasodilator)
How much blood is received by the kidney each minute?
• 1.1 litres of blood
What is general overflow aminoaciduria?
• All amino acids present in urine
• Due to inadequate deamination in the liver, or increased GFR
When is general overflow aminaciduria often seen?
• Early pregnancy
What is specific overflow aminoaciduria?
• Only a specific AA is present in the urine.
• This is usually do to a genetic inability to break down one AA
How can kidney stones develop as a result of renal aminoaciduria?
• Caused by dibasic acids, due to failure of transport system
• Cystein abnormally insoluble, and is strongly associated with kidney stone formation
• Cysteinuria associated with stone formation