Renal System

Question 1

The Renal System

Answer 1

renal system- integrative system

uses-
excretion of waste

regulate h20 and electrolyte balance

hormones

Question 2

5 renal functions

Answer 2

Removing waste products and drugs from the body by filtering the blood

Regulating the body’s fluid and electrolyte balance by increasing or decreasing the urine production

Producing hormones that regulate blood pressure, stimulate bone marrow to produce blood cells, and promote bone health

Producing an active form of vitamin D that helps the body absorb calcium

Maintaining the acid-base balance of the body by excreting excess acids or bases

Question 3

Kidneys

Answer 3

One of a pair of organs in the abdomen. The kidneys remove waste and extra water from the blood (as urine) and help keep chemicals (such as sodium, potassium, and calcium) balanced in the body. The kidneys also make hormones that help control blood pressure and stimulate bone marrow to make red blood cells

Question 4

Renal artery

Answer 4

blood waste and water enter the Kidney through renal artery

Question 5

renal vein

Answer 5

filtered blood or excess water leaves through the vein

Question 6

ureter

Answer 6

excess water and toxic waste leave in the form of urine

Question 7

Nephron

Answer 7

Nephrons are the structural and functional units of the
kidney. Each kidney has over 1 million of these units.

Each nephron consists of a renal corpuscle, which
contains the glomerulus (which is a tuft of capillaries)
and a renal tubule.

The tubule forms a cup shape around the glomerulus
called the glomerular capsule (Bowman’s capsule).

Question 8

Juxtaglomerular Apparatus

Answer 8

The juxtaglomerular cells are
mechanoreceptors (they sense blood pressure) in the afferent arteriole.

The macula densa cells are
chemoreceptors that respond to changes in the NaCl content of the filtrate.

Question 9

Basic Renal Processes

Answer 9

1. Glomerular Filtration
   ~20% of plasma entering GC is filtered
   into BC
2. Tubular secretion
3. Tubular reabsorption

Question 10

Differential Handling in the Kidney

Answer 10

The excretion of a substance is equal to the amount filtered plus the amount secreted minus the
amount reabsorbed.

Question 11

In summary

Answer 11

A substance can gain entry to the tubule and be excreted in the urine by
glomerular filtration or tubular secretion, or both
Once in the tubule, however, the substance does not have to be excreted
but can be completely reabsorbed
Thus: Amount excreted=
Amount filtered+
Amount secreted-
Amount reabsorbed

Question 12

Glomerular Filtration (GFR)

Answer 12

The GFR is the amount of blood filtered by the glomeruli each minute.
Factor influencing GFR

Capillary permeability [+]
Surface area (the size of the capillary bed)
Hydrostatic pressure that drives fluid out of the capillaries
Osmotic forces within the capillaries, which oppose the exit of fluid

Net filtration pressure = ∆P - ∆∏

Where ∆P is the transcapillary hydrostatic pressure gradient, and ∆π is the colloid osmotic pressure gradient.

Question 13

Glomerular Filtration (GFR)

Question 14

Glomerular Filtration

Answer 14

The kidney’s glomeruli are far more efficient
filter than other capillary beds in the body
because:
Filtration membrane is a large surface area and very
permeable to water and solutes.
Glomerular pressure is higher (~55 mm Hg), so they produce
180 L/day vs. 3-4 L/day formed by other capillary beds.
That’s 125 mL/min of total plasma volume (~3 L total PV)
Thus, kidney’s filter the entire PV ~ 60 times in a day!
Important During filtration plasma proteins remain in
plasma to maintain osmotic pressure.
Blood cells or protein in the urine (proteinuria)
indicates a problem with the filtration membrane.
Common finding during diabetes and hypertension and
signals that kidney damage has occurred. If untreated, will
progress to end stage renal disease and renal failure.

Question 15

Tubular Reabsorption

Answer 15

Tubular reabsorption begins as soon as filtrate enters the
tubule cells.
Paracellular transport occurs between cells (even though
they have tight junctions) and is seen mainly with ions.
Transport can be active (requires ATP) or passive (no ATP).

Question 16

Tubular Secretion

Answer 16

Substances such as hydrogen ion, potassium, and organic anions move
from the peritubular capillaries into the tubular lumen.
Tubular secretion is an important mechanism for:
1. disposing of drugs and drug metabolites.
2. eliminating undesired substances or end products that have reabsorbed by
passive processes (urea and uric acid).
3. removing excess K+.
4. controlling blood pH.

Question 17

“Division of Labour” in the Tubules

Answer 17

The majority of the reabsorption is accomplished by the proximal
tubule and the loop of Henle.
Extensive reabsorption by the proximal tubule and Henle’s loop
ensures that the masses of solutes and the volume of water entering
the tubular segments beyond Henle’s loop are relatively small.
These distal segments then do the fine-tuning for most substances,
determining the final amounts excreted in the urine by adjusting their
rates of reabsorption and, in a few cases, secretion.

Question 18

Renal Clearance (RC)

Answer 18

Renal Clearance (mL/min) is the amount of a substance filtered per minute, divided
by its plasma concentration. The clearance for any substance can be calculated.
RC=(U*V)/P
U=concentration of the substance in the urine (mg/mL)
V=flow rate of urine formation (mL/min)
P=concentration of substance in the plasma (mg/mL)
If the substance is freely filtered and not reabsorbed or secreted, this ratio allows us
to estimate the rate at which fluid is filtered at the glomerulus (that is, the GFR).
To determine RC we use inulin ( it’s freely filtered and neither reabsorbed nor
secreted).
Creatinine can be used but is less accurate.

Question 19

Calculating GFR

Answer 19

GFR=125ml/min

normal GFR=120ml/min

Question 20

Filtration fraction

Answer 20

The filtration fraction is the proportion of the plasma that enters the
kidneys that is subsequently filtered at the glomerulus and passes into
the renal tubules.
It is calculated from the ratio GFR/Renal Plasma Flow (RPF)
Filtration fraction is typically 0.16-0.20
Meaning, 20% of the blood that enters the kidneys is filtered

Question 21

Summary

Answer 21

Renal Function
The kidneys regulate the water and ionic composition of the body, excrete waste products,
excrete foreign chemicals, produce glucose during prolonged fasting, and release factors
and hormones into the blood
Structure of the Kidneys and Urinary System
Each nephron in the kidneys consists of a renal corpuscle and a tubule.
Each renal corpuscle has a glomerulus and a Bowman’s capsule.
The tubule extends from the Bowman’s capsule and is subdivided into the proximal
tubule, loop of Henle, distal convoluted tubule, and collecting-duct system.
At the level of the collecting ducts, multiple tubules join and empty into the renal pelvis,
from which urine flows through the ureters to the bladder.
Each glomerulus is supplied with blood by an afferent arteriole, and an efferent arteriole
leaves the glomerulus to branch into peritubular capillaries, which supply the tubule.

Question 22

summary

Answer 22

Basic Renal Processes
The three basic renal processes are glomerular filtration, tubular reabsorption, and
tubular secretion.
Glomerular filtrate contains all plasma substances other than proteins (and substances
bound to proteins) in virtually the same concentrations as in plasma.
Glomerular filtration is driven by the hydrostatic pressure in the glomerular capillaries and
is opposed by both the hydrostatic pressure in Bowman’s space and the osmotic force due
to the proteins in the glomerular capillary plasma.
As the filtrate moves through the tubules, certain substances are reabsorbed either by
diffusion or by mediated transport.
Tubular secretion, like glomerular filtration, is a pathway for the entrance of a substance
into the tubule.
Summary
The Concept of Renal Clearance
The clearance of any substance can be calculated by dividing the mass of the substance
excreted per unit time by the plasma concentration of the substance.
GFR can be measured experimentally by means of the inulin clearance and estimated
clinically by means of the creatinine clearance.

Question 23

Renal Sodium and Water Regulation
Renal response to exercise

Answer 23

title

Question 24

Fluid compartments of the body

Answer 24

Water makes up approximately 60% of our lean body weight
Our total body water is distributed within and outside our cells
2/3 of our total body water
is located within our cells
 intracellular fluid
The remaining 1/3 is
outside the cells
 extracellular fluid

Question 25

Basic Renal Processes for Sodium and Water

Answer 25

Sodium reabsorption is an active process occurring in all tubular segments except the descending limb of the Loop of Henle and the medullary collecting duct. Water reabsorption is by diffusion (i.e., osmosis) and is dependent upon sodium reabsorption (but not exclusively). Water moves through aquaporin channels. The presence of these aquaporins varies throughout the tubule segments. They are highly expressed in the proximal nephron. They are absent in the collecting ducts unless Anti-diuretic hormone (ADH) is active.

Question 26

Primary Active Sodium Reabsorption

Answer 26

Key points: * Active transport out of cells into interstitial fluid. * Transport achieved by Na+/K+-ATPase pump * Keeps intracellular conc. of Na+ low to allow ‘downhill’ movement of Na+ from lumen * Mechanism of Na+ movement across luminal membrane varies between tubule segments, whereas always via Na+/K+-ATPase pump for basolateral membrane * Proximal tubule (a): co-transport / counter- transport of organic molecules (glucose, aa) * Cortical collecting ducts (b): via Na+ channels

Question 27

Aquaporins: Key point summary

Answer 27

The regulation and function of AQPs in the medullary-collecting-duct cells is to increase water reabsorption. Anti-diuretic hormone (ADH) [aka vasopressin]) initiates a cascade of event within the collecting duct cells that leads to an increased number of AQP2 channels in luminal membrane, This allows increased passive diffusion of water into the cell. Water exits cell through AQP3 and AQP4, which are not vasopressin sensitive

Question 28

Antidiuretic hormone (ADH) and urine formation

Answer 28

ADH uses cAMP systems to cause the insertion of aquaporins into the membranes of the principle cells of the collecting ducts. So water flows out of the collecting ducts to be reabsorbed by the body. Regulation of ADH release from posterior pituitary gland. Most important of the inputs come from osmoreceptors (primarily) and baroreceptors Note – ADH is sometimes called Vasopressin

Question 29

Control of Sodium Reabsorption

Answer 29

Control of absorption is more important than the control of GFR for long-term regulation of Na+ excretion. Three factors determining the rate of tubular Na+ reabsorption: 1) Aldosterone (most major) 2) Atrial Natriuretic Peptide (ANP) 3) Local effect of blood pressure on the tubules High pressure also inhibits Na+ reabsorption (as well as reducing renin release – see next slide)

Question 30

1) Aldosterone and the Renin-Angiotensin System The Renin-angiotensin-aldosterone cascade

Answer 30

The release of the enzyme renin converts the peptide angiotensinogen to angiotensin I. Angiotensin I then converted to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II acts on angiotensin receptors located in several target tissues including the adrenal glands, kidneys, brain, and vasculature Activation of angiotensin receptors in the adrenal glands stimulates aldosterone release from these glands, which increase Na+ and H2O reabsorption

Question 31

2) Atrial Natriuretic Peptide (ANP)

Answer 31

ANP is synthesized and sorted in atrial myocytes ANP is released in response to stretching of the atria This occurs when our circulating blood volume increases An increase in circulating levels of ANP causes ↑ Na+ excretion

Question 32

Summary of Na+ and H20 regulation

Answer 32

Pathways by which decreased plasma volume leads to increased Na+ reabsorption; via the renin-angiotensin system and aldosterone

Question 33

Renal system’s role in regulating blood pressure

Answer 33

Sodium and H20 key in regulating blood pressure Note: » The regulation of body fluid osmolarity requires separation of water excretion from Na+ excretion » Made possible by two physiological factors: i. Osmoreceptors ii. Anti-diuretic hormone (ADH) dependent water reabsorption without Na+ reabsorption in the collecting ducts

Question 34

3) Local effect of blood pressure on the tubules

Answer 34

Baroreceptor regulation of blood pressure simultaneously regulates total-body sodium » See figure summarising major mechanisms wherein Na+ loss elicits a decrease in GFR. Recall: GFR is the volume of filtrate formed each minute. » This is affected by the volume of surface available, filtration membrane permeability and NFP (net filtration pressure), blood pressure / blood flow to the glomerular capillaries. » GFR is directly proportional to NFP. Therefore, increases (or decreases) in systemic blood pressure causes increases (decreases) in GFR

Question 35

Inputs Controlling Thirst

Answer 35

Because the kidney cannot create new Na+ or water, deficits must eventually be compensated for by ingestion of these substances

Question 36

Diuretics

Answer 36

Alcohol acts like a diuretic by inhibiting the release of Vasopressin from the pituitary gland. Diuretics can be medications use to help the body remove excess sodium and waterand help control blood pressure » Osmotic diuretics; carbohydrates that are filtered but not reabsorbed (ex. Mannitol). » Loop diuretics (lasix, furosemide) are the most powerful diuretics because they inhibit the formation of the medullar gradient by inhibiting Na+ reabsorption. » Hydrochlorithiazide acts on the distal collecting duct. » Spironolactone is an aldosterone receptor antagonist. This is known as a K+ sparing diuretic. It acts because the K+ in the urine is from aldosterone-driven active tubular secretion into the late DCT and collecting ducts. Diuretics are substances that promote the loss of Na+ and H2O

Question 37

Renal function during exercise

Answer 37

Renal blood flow decreases as soon as exercise starts Linear relaƟonship: ↑ exercise intensity = ↓renal blood flow However, GFR is only affected at exercise intensities above 50% VO2max A steady ↓ in GFR, down to 60% of the basal rate at maximal exercise.

Question 38

Renal Blood Flow

Answer 38

Increase sympathetic nervous system activity during exercise causes vasoconstriction of the renal arterioles. ↑ exercise intensity = ↑ sympatheƟc nervous system acƟvity = ↓renal blood flow Increase ADH (or vasopressin) release also reduces renal blood flow ADH causes renal vasoconstriction Remember that ADH release activity due to renin-angiotensin-aldosterone system Despite  renal blood flow, increase work for the kidney during exercise

Question 39

During exercise the kidneys

Answer 39

Maintain pH via loss of excess H+ in the urine Kidneys removes a small amount (2%) of total lactate produced during exercise Conserve body water fluid regulatory hormones act to increase water and Na+ reabsorption in the kidney Excrete metabolites H+ Creatinine (excess created from muscle breakdown) Other proteins

Question 40

Rhabdomyolysis

Answer 40

A condition where skeletal muscle cell damage can cause acute renal failure and sometimes death

Question 41

Rhabdomyolysis

Answer 41

Rhabdomyolysis is most often observed with novel, strenuous, overexertion » heat stress ↑ risk U.S. soldiers hospitalized for serious heat illness, 25% had rhabdomyolysis and 13% had acute renal failure. Carter et al., (2005) Med. Sci. Sports Exerc. 37:1338–1344 » dehydration likely ↑ risk When working or exercising in extreme or unusually hot conditions it is important to: » Maintain hydration by drinking water or rehydration solutions when thirsty » Stop if you feel unwell » Slow down your work rate or rest if needed

Question 42

Summary

Answer 42

Basic Renal Process for Sodium and Water The body gains H2O via ingestion and metabolism, it loses H2O via urine, the gastrointestinal tract, and evaporation from the skin and respiratory tract. The body gains Na+ and Cl− by ingesƟon and loses them via the skin (in sweat), the gastrointestinal tract, and urine The renal system is the major homeostatic control point for controlling H2O and Na+ Renal Na+ reabsorption Baroreceptor regulation of blood pressure simultaneously regulates total-body Na+ Aldosterone controls tubular Na+ reabsorption The renin–angiotensin system is one of the two major controllers of aldosterone secretion ANP also controls Na+ reabsorption Renal H2O reabsorption Baroreceptor regulation of blood pressure simultaneously regulates H2O excretion Main controller of water reabsorption is ADH