The Kidneys

Question 1

Kidneys are largely associated with

Answer 1

The removal of wastes, but among the most important function are the regulation of proper fluid water and electrolyte/ion continent which will influence homeostasis of blood pressure and osmolarity/ph

Question 2

The functions of the kidneys rely on

Answer 2

The concept of mass balance one in one out. I generally lump most of the functions and to what I called the urine production but keep in mind that I’m referring to many of these functions.

Question 3

Primary functions of the kidneys (6)

Answer 3

1. Regulation of extracellular fluid volume and blood pressure
2. Regulation of osmolarity
3. Maintenance of ion balance
4. Homeostatic regulation of pH
5. Excretion of waste
6. Production of hormones

Question 4

Regulation of extracellular fluid volume and blood pressure

Answer 4

Primary function of the kidneys: ECF , blood volume, and mean arterial pressure and remember that proper MAP is critical to perfusion of the organs.

Question 5

Regulation of osmolarity

Answer 5

Ideal blood/ECF osmolarity is about 290 Mili Osmo‘s which is maintained through removal of ions (eg. behavioral mechanisms examples thirst fluid intake,) when too high and retaining/absorbing them when Too low

Question 6

Maintenance of ion balance

Answer 6

Certain ions mainly sodium are closely monitored to maintain proper levels. Potassium and calcium are also monitored.

Question 7

Homeostatic regulation of pH

Answer 7

In addition to mechanisms in the respiratory system kidneys help maintain plasma PH through balance of removal and retention, excretion and reabsorption of hydrogen and bicarbonate

Question 8

Excretion of wastes

Answer 8

Metabolic wastes such as creatinine urea and uric acid along with certain chemicals, food preservatives, artificial sweeteners, Is removed from the body in urine which is hopefully you already know produced by the kidneys

Question 9

Production of hormones

Answer 9

Hormones such as EPO and enzymes such as renin and those responsible for converting Calcidiol into calcitriol (vitamin D3) for a calcium homeostasis

Question 10

Recall that there are two types of nephrons

Answer 10

Cortical and juxtamedullary that form urine by filtering fluids from plasma and then regulate what to keep/reabsorb and want to get rid of/secrete through actions within the regions of the nephron. PCT, nephron loop, DCT

Question 11

Thick and thin regions (of the nephron tubules)

Answer 11

have different permeability‘s to ions and water

Question 12

Blood enters the

Answer 12

Renal corpuscle through and an afferent arterial into the glomerulus and leaves through the Efferent arterial where it forms a portal system with the peritubular capillaries and Vasa Recta of juxtamedullary nephrons before returning blood to the general circulation.

Question 13

Another important structure is the

Answer 13

Juxtaglomerular apparatus (JGA A.k.a. Juxtaglomerular complex JGC) which is made up of the final region of the ascending nephron loop and the afferent an Efferent arterials. The JGA is a major point of monitoring and comparing fluid in the nephron to plasma that allows communicating what changes may need to take place in order to maintain proper fluid/ion levels

Question 14

There are three basic processes involved with urine production

Answer 14

1. Filtration/bulk movement of fluid from blood into renal tubule‘s
   2. Reabsorption/pulling stuff from the tubule back into the blood that we want to keep
2. Secretion/for the removal of stuff from blood into the tubule that we want to get rid of.
3. And finally excretion which is the final removal of urine from the body through micturition.

Overall you may think of urine production as: excreted urine = filtration - reabsorption + secretion

Question 15

Filtration occurs in the

Answer 15

Renal corpuscle as fluid is pushed out of the glomerulus into the glomerular capsule a.k.a. Bowmans capsule forming filtrate. This process is non-specific about 20% of the plasma term of the filtration fragment moves into the capsule, larger elements such as blood cells and plasma proteins do not leave the blood, so most of the filtrate is water small molecules such as amino acids glucose urea and ions

Question 16

Fluid passes through three layers between glomerulus and capsule

Answer 16

Fenestrated capillary endothelium, basement membrane (between the endothelium and capsular layer), and between the processes of the podocytes that form filtration slits.

Question 17

Structural mesangial cells

Answer 17

Help hold the capillaries together in the glomerulus and are able to modify filtration by altering the surface area of filtration slits

Question 18

Glomerular filtration rate GFR

Answer 18

The amount of fluid moves from the blood into the capsule per unit time (average 180 L per day) and is largely influenced by outward pushing hydrostatic blood pressure (PH) from within the glomerular capillaries. However colluded osmotic pressure (pie) and fluid pressure from the capsule (Pfluid) oppose (pH) and want to to pull/push fluid back into the capillaries.
*similar to the bulk exchange in capillary beds

Question 19

The main goal of GFR

Answer 19

Is to always have a net filtration/positive GFR from the blood into the capsule, if you have fluid moving from the capsule into the blood that’s not good

Question 20

Homeostatic controls will do everything they can to maintain

Answer 20

A high enough hydrostatic pressure (pH) to outweigh the pressures of (pie) and (Pfluid) and keep things moving in the right direction and maintaining a relatively constant GFR

Question 21

Net filtration pressure

Answer 21

}GFR =Ph-pie-Pfluid

Question 22

How does the body make sure hydrostatic pressure is greater than

Answer 22

Pie-Pfluid? Mean arterial pressure: within a normal range of mean arterial pressure greater than 80 less than 180 MMHG, GFR remains relatively constant through micro controls of the following mechanisms in general increase map causes an increase in GFR similarly if blood is diverted away from the kidneys decrease renal perfusion causes a decrease in GFR

Question 23

If mean arterial pressure changes

Answer 23

The kidneys can adjust blood flow into the glomerulus to maintain GFR through
•vasoconstriction of afferent arterial: decrease glomerular blood flow which decreases GFR
•Vasodilation of afferent arterial: increase glomerular blood flow which increases GFR
• vasoconstriction of Efferent arterial: decreases glomerular blood flow which increases GFR (this one is weird so think about it for a minute, by slowing the outward flow blood backs up in the glomerulus which increases glomerular pH and increases GFR)

Question 24

Blood loss dehydration, overhydration etc. will influence

Answer 24

MAP, so if/when MAP changes the kidneys modulate renal blood flow to maintain GFR.

Question 25

Regulation of GFR occurs through a few mechanisms (3)

Answer 25

1. Auto regulation takes place through two mechanisms:
   - myogenic responses: stretching of vascular smooth muscles due to increased MAP stimulates contraction/ Vasoconstriction this only works with MAP above 80 MMHG.
   - tubuloglomerular feedback: complex interaction between macula densa and granular cells (a.k.a. juxtaglomerular cells) of the JGA; monitoring the tubular filtrate flow and osmolarity cause macula densa to release paracrine signals causing construction of Afferent arterial which decreases blood flow causing a decrease and GFR.
2. Hormonal control: includes angiotensin two (vasoconstrictor) and prostaglandins (vasodilator‘s) which affect overall systemic arterial resistance (including MAP and GFR)
3. Sympathetic nervous system: normally has a small role in GFR, but if sudden drop in MAP occurs due to blood loss, vasoconstriction of afferent an efferent arterials occurs to lower GFR conserve fluid loss and maintain blood pressure.

Question 26

Reabsorption is a specific process

Answer 26

Compared to filtrate which is non-specific, 180 L per day of fluid is filtered at the glomerulus but only 1.5 L of urine is excreted per day. Meaning that 99% of the filtered fluid is reabsorbed back into the body

Question 27

Why does the body filter everything then reabsorb

Answer 27

Rather than simply secrete stuff it doesn’t want, think about cleaning out a closet it makes more sense to pull everything out then only keep the select things you know you want to hold onto. Another consideration is that if the body selectively secreted substances if you were given something that the body didn’t know how to secrete didn’t have a specific transporter for that substance would accumulate in the body better to get rid of everything just in case

Question 28

Most reabsorption occurs in the

Answer 28

PCT proximal convoluted tubule and is driven by the active transporter using ATP of sodium from filtrate into the ECF, other molecules use sodium to hitch a ride via cotransporters (symporters and antiporters) or follow the gradient (electro chemical or concentration) that’s created when sodium is removed from the filtrate. First sodium is actively removed, then anion‘s passively follow the electrical chemical gradient created, then water passively follows The concentration gradient created. Then because the filtrate concentration has changed other ions will passively diffuse into the ECF

Question 29

Primary active (direct) transport of sodium

Answer 29

The first part of sodium reabsorption is actually passive sodium concentration in the filtrate is higher, but low inside the tubular epithelial cell, so it diffuses into the cell. However because ICF sodium concentration will keep increasing and stop this process, sodium needs to be removed on the basal lateral side of the cell into the ECF through sodium potassium pump using ATP directly

Question 30

Secondary (indirect) active transport

Answer 30

Some molecules Glucose, amino acids, lactate, ions use the driving energy that moves sodium into the cell to hitch a free ride into or out of the sell by using cotransporters.
Example glucose is transported into cells against its concentration gradient using the sodium glucose cotransporter SGLT proteins symporter. On the basal lateral side of the cell, glucose then diffuses out of the cell down its concentration gradient through facilitated diffusion using the GLUT proteins transporter. Other molecules use similar mechanisms to glucose transport some transporters use hydrogen instead of sodium

Question 31

Passive transport

Answer 31

As other molecules, ions, water leave the filtrate, urea becomes more concentrated in the filtrate, creating osmotic concentration gradient. Because of this area well then possibly diffuse from filtrate into the ECF in intracellular or paracellular pathways

Question 32

Endocytosis

Answer 32

Small proteins and polypeptides with a small enough to be filtered are we absorbed through receptor mediated endocytosis. Cells take up the proteins into lysosomes where they are broken down into amino acids -one way that peptide signal molecules are broken down

Question 33

Reabsorption is limited by

Answer 33

Saturation (transport maximum Tm) of transporters- if there is too much of a substance in filtrate, the transporter cannot move it all in and it gets excreted in urine. Glucose is an example of this especially in diabetics the bodies cells are unable to absorb all of the circulating glucose so it ends up being filtered at the glomerulus, ends up in filtrate, transporters get maxed out, and glucose ends up in the urine termed glucosuria

Question 34

Normal Blood Glucose range is between

Answer 34

100 to 200 mg/dL and is 100% reabsorbed in the PCT (at a maximum rate of about 375 mg/min = Tm)

Question 35

If blood glucose exceeds transport maximum (Tm)

Answer 35

Transporters become saturated and glucose is excreted in urine. This level when glucose levels exceed what is able to be fully reabsorbed is termed *renal threshold representing the point at which TM is reached and excretion of the substance begins

Question 36

Once substances are reabsorbed from filtrate into the ECF

Answer 36

The low pH in peritubular capillaries favors absorption back into the blood. Recall book exchange in capillary beds from chapter 15. Peritubular pH= 10 MMHG; pie= 30mm Hg> pressure gradient =-20 mmHg (=net absorption)

Question 37

Secretion is a mostly selective process that relies on

Answer 37

Active transporters along the PCT, DCT, and nephron loop to remove substances from ECF and put them into the filtrate and allow concentrating substances in the urine that we want to get rid of example potassium and hydrogen can be selectively secreted to help maintain their homeostatic levels. Likewise organic tablets or xenobiotics foreign are secreted into filtrate to become excreted in urine

Question 38

Note that some substances may be secreted in one part

Answer 38

Of the nephron and then reabsorbed in another part allowing fine-tuning of what is removed and what is kept.
The processes are complex and rely on multiple indirect active transporters to move substances up against a concentration gradients example primary active transporters use ATP secondary, tertiary transporters use gradients established by the primary transporters to do their work

Question 39

Organic anion transporters OATS

Answer 39

Are a class of transporters used to secrete a variety of organic substances through indirect active transport

Question 40

The four types of organic anion transporters

Answer 40

1. Sodium potassium pump primary direct active transport it moves sodium from ICF to ECS keeping ICF sodium concentration low
2. Sodium die carboxylate cotransporter (NADC, secondary indirect active transporter) uses the sodium Gradient established by the primary transporter to move dicarboxylate anions (metabolic intermediates such as alpha -ketoglutarate from the citric acid cycle) into the ICF creating a concentration gradient
3. Organic anion transporter (OAT 1-3 3• indirect active transporters) move organic anion from ECF into ICF using concentration gradient established by secondary transporter.
4. OAT4 (facilitated diffusion transporter) move organic anions from anions from ICF into filtrate.

Question 41

Excretion is the removal of

Answer 41

Everything left infiltrate that either hasn’t been reabsorbed or was secreted into it, basically urine

Question 42

The composition of urine will change depending on

Answer 42

The metabolic state in order to maintain homeostasis

Question 43

How the kidneys deal with a particular substance

Answer 43

Filtration rate and what extent is reabsorbed, secreted or both is termed renal handling

Question 44

Glucose is normally

Answer 44

100% actively reabsorbed in the PCT, none is excreted if it is it’s pretty clear indication of a problem

Question 45

Sodium, chloride, potassium, calcium are mostly reabsorbed

Answer 45

In the PCT, nephron loop, and DCT. Again depending on levels in the body their reabsorption and excretion are regulated

Question 46

Urea is reabsorbed in the

Answer 46

PCT and DCT, but secreted in the nephron loop so the amount excreted will vary between 30 to 50%

Question 47

PAH para Aminohippurate is used for

Answer 47

An organic anion used in physiological test for renal clearance, None is reabsorbed and 100% is actively secreted in the PCT 100% is excreted

Question 48

Renal handling and GFR have clinical significance

Answer 48

Drugs must be analyzed for how they are processed by the kidneys before getting FDA approval. Likewise GFR can indicate kidney function which can indicate how close someone is to their end-stage Death

Question 49

Clearances one way to estimate

Answer 49

GFR/kidney function and renal handling of substances by comparing it to other known substances just by comparing the concentration of a substance and blood to its concentration in urine

Question 50

Clearance of X =

Answer 50

Excretion of X (mg/min) / plasma [X] (mg/ml plasma)

This is a little tricky concept to wrap your head around clearance is the rate of a substance that is removed from plasma by the kidneys

Question 51

Inulin

Answer 51

Not to be confused with insulin as a plant polysaccharide that can be used administered via IV to estimate GFR. It has a clearance of 100%. It is filtered at the glomerulus and is neither reabsorbed nor secreted. Compared to PAH which is not reabsorbed but Is actively secreted.

Question 52

Filtered load

Answer 52

The amount of a substance that is removed/excreted by clearance.

Filter load (excretion) of inulin = plasma [inulin] x GFR 

Question 53

We can calculate the amount filtered by using the concentration of inulin found

Answer 53

In urine/the amount excreted, we know the concentration in plasma because we’re administering that amount so if we’re rearranging the equation we get:

GFR = excretion of inulin /plasma [inulin] = inulin clearance

Question 54

Take home messages for clearance

Answer 54

If clearance of substance X < GFR = net absorption of X

If clearance of substance X > GFR = net secretion of X

If clearance of substance X = GFR = neither (no net change) 

Question 55

Creatinine is used as a proxy to estimate GFR by

Answer 55

The breakdown of phosphocreatine and constantly excreted in urine, does not need to be administered intervenous it’s less per size fits relatively easy way to estimate GFR and again GFR is important diagnostic tool