Kidney structure 1+2 Flashcards
What does the urinary system do?
Remove wastes from blood
Kidneys make urine, while other organs store & transport urine
Maintain water and electrolyte balance
Maintain acid-base balance
Regulates BP renin-angiotensin-aldosterone system (RAAS)
Help in RBC production (EPO)
Kidneys involved in gluconeogenesis
What is the structure of the kidneys?
Renal pyramid, Renal medulla, Renal cortex, Renal pelvis and Ureter.
functional unit in kidney= nephron
More structure and function
proxomal tubule=reabsorption
loop of Henle=good for building up osmolarity.
counter current multiplier effect
any dessert animal os more likely to have longer loops of Henle so that they can have a greater osmolarity in their kidney and absorb more water, pee is more concentrated.
The nephron
The nephron is the structural and functional unit of the kidney
Each kidney has approximately 1 million
They cannot be regenerated
After 40 years of age, they decrease in number
What are the two types of nephrons?
cortical nephrons =found in outer cortex
juxta medullary=responsible for making counter current mechanism
What is the normal osmolarity of the blood
what’s the pH of blood?
300 mmHg (osmoles)
7.4
nephron Blood supply
what is cardiac output of heart to the kidneys
first set of capillary is used for filtering and peritubular capillaries are used for reabsorption.
The nephron is covered with capillaries.
cardiac output=22% (1/5)
What is the Urine formation equation?
What do you get rid of in?
what does not get filtered?
Urine = Filtration - Reabsorption + Secretion
we filter sugar through the bowman’s capsule as its small and uncharged. No sugar should be passed as urine.
Urea and water
large proteins, red or white blood cells
All substances in the plasma, undergo a form of filtration, reabsorption and secretion.
These 3 basic renal processes determine the rate at which substances are excreted in the urine.
These processes are all regulated according to body needs
Glomerular filtration rate (GFR)
biomarker of kidney health it is the filtration rate
An advantage of the GFR is that waste products use a high GFR to get filtered, secondly, the entire plasma volume (3 l) can be filtered 60 times/day to allow precise control on volume and composition of body fluids.
How much GFR per minute
Glomerular Filtration Rate
GFR = 125ml/min
= 180 l/day in humans
Urine production = 1.5 l/day
GFR is usually accepted as the best overall index of kidney function in health and disease
Glomerular filtration
Glomerular capillaries are relatively impermeable to proteins, so the glomerular filtrate is free from proteins and cells
Salt and organic molecule concentrations in this filtrate are the same as plasma, except, some
substances which are bound to plasma proteins.
About half [Ca2+] and most fatty acids are attached to these proteins and they are not filtered through the glomerular capillaries.
What determines GFR
GFR is determined by:
The balance of hydrostatic and colloid osmotic forces across the capillary membrane (net filtration pressure)
The capillary filtration coefficient (Kf), which is the permeability multiplied by the filtering surface area of the capillaries
What are the pressures?
Glomerular hydrostatic pressure 60mmHg
glomerular colloid osmotic pressure 32mmHg
Bowman’s capsule pressure 18mmHg
Glomerular Hydrostatic Pressure (GHP): Promotes filtration of fluid and solutes from blood into Bowman’s capsule.
Capsular Hydrostatic Pressure (CHP): Opposes movement of additional fluid and solutes into renal tubules.
Blood Colloid Osmotic Pressure (BCOP): Due to proteins in blood, it opposes filtration by pulling water back into glomerular capillaries.
Capsular Colloid Osmotic Pressure (CCOP): Osmotic pressure in renal tubules that encourages reabsorption of water and solutes.
4 pressures interstitial fluid which would have osmotic pressure but not in kidney as membrane is very selective and does not allow for loads of larger proteins to come through.
Equation incorporating GFR, KF and net filtration pressure
GFR = Kf x net filtration pressure
Due to a high hydrostatic pressure & Kf, glomerular capillaries have a filtration rate more than other capillaries.
capillaries in kidney are leaky and very permeable unlike capillaries elsewhere in the body.
Give equation for GFR, filtration fraction and renal plasma flow
19 % of the plasma flowing through the glomerular capillaries is filtered. Therefore the filtration fraction = 0.19.
filtration fraction= GFR/renal plasma flow
So, renal plasma flow ≈ 650 ml/min
Definition and normal values of GFR
Definition = Volume of fluid filtered from the renal glomerular capillaries into the Bowman’s capsule in both kidneys per unit time.
The normal range of GFR is:
Males: 97 to 137 ml/min
Females: 88 to 128 ml/min
If GFR would grossly change, then this would affect water and solute excretion e.g. if arterial BP increased from 100 to 125 mmHg, GFR would also go from 180 to 225 l/day
If tubular reabsorption was constant, at 178.5 l/day, 46.5 litres would have to be excreted daily!
What happens to GFR when you get older
As you get older, the average GFR number drops. So age, sex, race and body size affect GFR
However, a GFR with a value < 60 ml/min suggests some kidney damage has occurred
When Kf (coefficient of permeability) is compared on a weight-for-weight basis with other organs, it is 400 times greater in the kidney.
This helps these capillaries rapidly filter blood
In DM (diabetes mellitus) and chronic hypertension, Kf is reduced, as the basement membrane thickness is increased
Eventually, capillaries are damaged, and their function is severely affected, which decreases their permeability
Describe processes of blood going into the kidneys
When blood comes from the heart to the kidneys through the afferent arteriole, it’s loaded with oxygen and nutrients. In the tiny capillaries of the kidney, about 90% of the fluid in the blood (now called filtrate) will leave. This filtrate is very similar to blood in terms of sodium, glucose, urea, potassium, and osmolarity.
However, it’s important to note that the filtrate won’t contain cells, plasma proteins, or fatty acids, which are normally found in the blood. The kidney is like a smart filter, allowing essential substances to pass through while holding onto important components your body needs.
Glomerular Capillary
Podocyte foot process
Filtration slit
Basement membrane
Capillary pore
all slightly negatively charged
Albumin
albumin (proteins)
used as biomarker
with patients with kidney disease there higher albumin filtered, reabsorbed. In a normal person there shouldn’t be any proteins in the urine but with kidney disease there is.
Effect of Increased Blood Pressure on Filtration
Arterial blood pressure (increases blood flow into the glomerulus)
so GFR has higher glomerular capillary blood pressure and higher net pressure therefore higher GFR.
Vasoconstriction (decreases blood flow into the glomerulus)
So what happens to the GFR
It will also decrease
Vasodilation (increases blood flow into the glomerulus)
GFR increases too
autoregulation
The kidney always try to keep GFR to a level.
Eventually with high pressure they can become leaky and lose proteins
you can also have the efferent artery vasodilating and vasoconstricting.
Summary
Kidney function is part of the bigger process of salt and water balance
Fundamental processes are filtration, reabsorption, tubular synthesis, secretion
Loop of Henle is for producing hyper-osmotic urine
The molecular basis of solute transport
Inulin used to estimate GFR
Inulin is as freely filtered as water and it is not reabsorbed or secreted
So, its urinary excretion rate is equal to its kidney filtration rate
it can be a good marker for GFR
What is inulin
Inulin is a plant polysaccharide that is used to estimate GFR. Its mol. Wt. is ≈ 5200 and it is given intravenously.
When inulin = 1 mg/ml, inulin = 125 mg/ml and urine flow rate is 1 ml/min, then 125 mg of inulin pass into the urine per min (see fig.).
Higher GFR high concentration of inulin in the urine as higher amount of inulin gets filtered.
The only disadvantage is that its invasive and you have to inject intravenously.
GFR = Uinulin x V Pinulin
GFR = 125 x 1 = 125 ml/min
1
Inulin clearance is the urinary excretion rate divided by the plasma [inulin], equaling 125 ml/min. So, 125 ml of plasma must be filtered by the kidneys to deliver the inulin that is secreted in the urine.
Creatine, cystatin C and iothalamate
Clinically, creatinine, cystatin C and iothalamate are used to estimate GFR. As creatinine is a muscle metabolite, and is normally found in plasma, it is commonly used
However, a small amount is secreted by the tubules, so the amount in the urine is more than actually filtered
sometimes EGFR as its estimate GFR
Creatinine clearance measurement requires collection of a timed urine sample; can be inconvenient/inaccurate
Repeat measurements can overcome some of the errors
So overall, creatinine clearance does give a satisfactory estimate of GFR
its non-invasive, not foreign so no risk of allergic reactions
Tubular Processing
Urinary excretion is equal to glomerular filtration and tubular secretion minus tubular reabsorption. For most substances, reabsorption is more important, though for others, like H+ and K+, secretion is more important.
The filtration rate of freely filtered substances = GFR x PS. However, the substance must be freely filtered and must not be bound to plasma proteins.
For example: P glucose = 1 g/l
Glucose filtered/day = 180 l/day x 1 g/l = 180 g/day
This is also the amount reabsorbed as 100 % of glucose is reabsorbed.
the brain needs lots of glucose
The main electrolyte in our body and brain cells is potassium. Plant and meat products also contain lots of potassium so we have a lot of that and protons in our diet therefore secretion of these electrolytes is more important
amino acids are very important, they are an expensive commodity
bicarbonate is almost all reabsorbed
sodium and chloride are also highly reabsorbed
Tell me about filtration and reabsorption
Filtration and reabsorption are quantitatively large for many substances
Reabsorption, unlike filtration, is highly selective
So, by controlling reabsorption the kidneys regulate body fluids.
Reabsorption of water and solutes occurs across tubular cells, interstitium, and finally the peritubular capillary membrane, using active and passive mechanisms. They can follow several routes to enter the interstitium:
Transcellular (through cell)
or
Paracellular (through tight junctions)
From the interstitium, solutes and fluid enter the blood by bulk flow or ultrafiltration; helped by hydrostatic and colloid osmotic forces.
Active transport
Active moves a solute against its electrochemical gradient and needs energy e.g. 1o active transport for Na+ reabsorption in the PT, on the basolateral side. This keeps Na+ low inside the cell, so more Na+ can enter from the luminal side.
sodium active transport
It is also electrogenic, attracting more Na+ inside. 2o active transport also occurs, e.g. Na+/glucose or amino acid reabsorption (see fig.). The energy is the movement of Na+ down its electrochemical gradient. H+ is secreted into the tubules using 2o active transport.
Transport maximums
some solutes have transport maximums
Substances that are actively reabsorbed or secreted, are limited by the number of carrier proteins e.g. glucose
The filtered load of glucose = GFR x Pglu
= 125 x 1 = 125 mg/min. The Tmax is 320 mg/min. If either GFR or Pglu go up,
above the Tmax, then glucose will not be totally reabsorbed & it will enter the urine. However, when the load rises above 220 mg/min, some glucose does enter the urine (threshold). This can be due to not all nephrons having the same transport maximum, as the Tmax is an overall value for the kidneys.
(if glucose level goes higher, there are limited number of glucose transport proteins so there is a transport maximum so it won’t get reabsorbed and get excreted).
every substance has a transport maximum
What about substances that are passively reabsorbed?
Substances that are passively reabsorbed do not have a Tmax, and depend on:
The electrochemical gradient
Membrane permeability
Tubular flow rate
Osmosis
Osmosis of water follows the direction of the solutes being transported
Osmosis takes place through tight junctions and also the cells (paracelularly)
The tight junctions in the PT are not very tight (they are called leaky) to water and solutes
Osmosis also takes solutes with it (solvent drag), though this is affected by sodium reabsorption
In the latter parts of the nephron, the junctions become more tight (less leaky)
ADH (antidiuretic hormone) can affect water permeability in the DCT (distal cortical tubule) (end of nephron) and collecting tubules
Sodium reabsorption
Sodium reabsorption makes chloride ions follow paracellularly. Chloride and urea also get concentrated in the tubule as osmosis is taking place
This helps them get passively absorbed, though chloride reabsorption is a lot more than urea
PT (proximal tubule) reabsorption
Here, 65 % of sodium and water is reabsorbed. The cells are rich (lots of organelles, large and thick) and have brush border
In the first half of the PT, sodium is reabsorbed with glucose & amino acids, and in the other half, chloride comes with it
As the tubular fluid moves across the PT, the [sodium] and osmolarity are constant, as both water and sodium are being reabsorbed
PT also secretes bile salts, oxalate, urate, PAH, catecholamines (dopamine), toxins and drugs (including aspirin & penicillin)
Graph
massive amount of reabsorption
Loop of Henle
The thin descending & ascending segments have thin epithelia, though the thin descending is highly permeable to water and moderately so to solutes
About 20 % of water is reabsorbed here
The thin and thick ascending are almost impermeable to water
The thick ascending segment reabsorbs 25 % of all sodium, chloride and potassium. Cations also are reabsorbed here paracellularly, as the lumen has a positive charge (due to K+ ions)
As water is not reabsorbed here, the tubular fluid is dilute as it goes to the DT
basolateral side=renal interstitial fluid side
DT reabsorption
The first part of the DT is part of the JGA. The early part of the DT absorbs most ions but is impermeable to water and urea, so it again dilutes the tubular fluid
The late DT and the cortical collecting tubule (CCT) are similar but can reabsorb water
Both have two types of cells: to help us get rid of acids (H+)
Principal cells
Intercalated cells
Principal cells reabsorb water and sodium and secrete potassium. The intercalated cells reabsorb potassium and secrete hydrogen using an ATPase (useful in acid base control)
The DT and CCT can alter their sodium reabsorption by aldosterone
Also, water reabsorption can be affected by ADH, as with no ADH, these parts are almost impermeable to water
Medullary Collecting duct (MCD)
The MCD absorbs less than 10 % of water and sodium, but is important to form the final urine
ADH can affect water reabsorption and also hydrogen can be secreted here. Urea can also be absorbed to help concentrate the urine.
