Kidney structure 1+2

Question 1

What does the urinary system do?​

Answer 1

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​

Question 2

What is the structure of the kidneys?

Answer 2

Renal​ pyramid​, Renal​ medulla​, Renal​ cortex​, Renal​ pelvis​ and Ureter​.

functional unit in kidney= nephron

Question 2

More structure and function

Answer 2

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.

Question 2

The nephron​

Answer 2

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​

Question 3

What are the two types of nephrons?

Answer 3

cortical nephrons =found in outer cortex
juxta medullary=responsible for making counter current mechanism

Question 4

What is the normal osmolarity of the blood
what’s the pH of blood?

Answer 4

300 mmHg (osmoles)
7.4

Question 5

nephron​ Blood supply​​
what is cardiac output of heart to the kidneys

Answer 5

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)

Question 6

What is the Urine formation​ equation?
What do you get rid of in?
what does not get filtered?

Answer 6

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​

Question 7

Glomerular filtration rate (GFR)​

Answer 7

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.​

Question 8

How much GFR per minute

Answer 8

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​

Question 9

Glomerular filtration​

Answer 9

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.​

Question 10

What determines GFR

Answer 10

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​

Question 11

What are the pressures?

Answer 11

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.

Question 12

Equation incorporating GFR, KF and net filtration pressure

Answer 12

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.

Question 13

Give equation for GFR, filtration fraction and renal plasma flow

Answer 13

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​

Question 14

Definition and normal values of GFR​

Answer 14

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! ​

Question 15

What happens to GFR when you get older

Answer 15

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​

Question 16

Describe processes of blood going into the kidneys

Answer 16

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.

Question 17

Glomerular Capillary​

Answer 17

Podocyte foot process​
Filtration​ slit​
Basement​ membrane​
Capillary​ pore​

all slightly negatively charged

Question 18

Albumin

Answer 18

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.

Question 19

Effect of Increased Blood Pressure on Filtration​

Answer 19

Arterial blood ​pressure​ (increases blood ​flow into the ​glomerulus)​
so GFR has higher glomerular capillary blood pressure and higher net pressure therefore higher GFR.

Question 20

Vasoconstriction​ (decreases blood flow into the glomerulus)
So what happens to the GFR​

Answer 20

It will also decrease

Question 21

Vasodilation​ (increases blood flow​ into the glomerulus)​

Answer 21

GFR increases too

Question 22

autoregulation

Answer 22

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.

Question 23

Summary

Answer 23

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​

Question 24

The molecular basis of solute transport ​

Answer 24

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

Question 25

What is inulin

Answer 25

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.​

Question 26

Creatine, cystatin C and iothalamate

Answer 26

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

Question 27

Tubular Processing​

Answer 27

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

Question 28

Tell me about filtration and reabsorption

Answer 28

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. ​

Question 29

Active transport​

Answer 29

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.​

Question 30

sodium active transport

Answer 30

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. ​

Question 31

Transport maximums​

Answer 31

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

Question 32

What about substances that are passively reabsorbed?

Answer 32

Substances that are passively reabsorbed do not have a Tmax, and depend on:​

The electrochemical gradient​
Membrane permeability​
Tubular flow rate​

Question 33

Osmosis​

Answer 33

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​

Question 34

Sodium reabsorption

Answer 34

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​

Question 35

PT (proximal tubule) reabsorption​

Answer 35

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)​

Question 36

Graph

Answer 36

massive amount of reabsorption

Question 37

Loop of Henle​

Answer 37

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

Question 38

DT reabsorption​

Answer 38

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​

Question 39

Medullary Collecting duct (MCD)​

Answer 39

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.