Renal Revision (Wk: 2)

Question 1

What are the kidneys located and at what level in the verebral column?

Answer 1

• retroperitoneal space, just behind the abdominal peritoneum.
• each side of vertebral column between T12 and L3.
• They are surrounded by a layer of adipose tissue, termed a capsule, and held in place by the renal fascia.
• R) kidney sits lower than L) due to position of liver.

Question 2

Estimate the general size of the kidney

Answer 2

• 12cm long, 6cm wide and 2.5cm thick
  Weight: 125-170 grams in men, 115-155 grams in women

Question 3

Recall the three major section of the kidney and their respective function?

Answer 3

1. Cortex
   - contains the majority of nephrons (functional units), glomeruli, convoluted tubules and the collection ducts.
2. Medulla
   - inner part comprised of columns, pyramids and calyces which together receive urine from the entry into the renal pelvis.
3. Renal pelvis
   - collects the ureters for urine to flow into the bladder.

Question 4

Describe the nephron and its components

Answer 4

= a tubular structure containing a funnel-shaped unit called the glomerular capsule (Bowman’s capsule). The capsule has two layers - parietal and visceral.
- The space between the layers is referred to as the glomerular space.

Question 5

What are the three layers the glomerular filtration membrane is comprised of? and describe the process though it

Answer 5

1. endothelium of the capillary
2. visceral layer of the glomerular capsule (contains podocytes)
   - holds the glomerulus, where blood enters the nephron to start the filtration process
3. basement membrane between the 2 layers
   - Fluid moves from capillaries into the capsule for filtration

Question 6

Describe the path of filtration through the nephron

Answer 6

• The glomerular capsule holds the glomerulus, where blood enters the nephron to start the filtration process. - Fluid moves from capillaries into the capsule for filtration.
• From there, fluid moves through the proximal convoluted tubule, loop of Henle (nephron loop), and the distal convoluted tubule.
• The distal convoluted tubule then drains into the collecting duct, which contributes to urine formation.

Question 7

Describe the blood supply to the kidney

Answer 7

• mimics the structure of the nephrons.
• Renal arteries divide into interlobar arteries and then into arcuate arteries, including the afferent and efferent arterioles which enter and exit the glomerulus.
• Glomerular capillaries carry blood to the peritubular capillaries which reabsorb fluid and solutes from the tubules which drain into the renal vein.

Question 8

What is the primary function of the kidney?

Answer 8

= maintain a stable internal environment for optimal cell and tissue metabolism by balancing outputs (solutes and water) with inputs, resulting in excreting metabolic waste products, conserving nutrients, and regulating acid and bases.

Question 9

What are some of the primary purposes of the kidney?

Answer 9

• Regulate body fluid volume and osmolality
• Regulate electrolyte balance
• Regulate acid-base balance (in conjunction with body buffer systems and respiratory system)
• Remove metabolic wastes such as urea, creatinine, uric acid, and more
• Regulate blood pressure
• Produce erythropoietin hormone (to regulate bone marrow production of red blood cells)
• Activate Vitamin D to its physiologically active form
• Perform gluconeogenesis (synthesis of glucose)
• Synthesise hormones, such as prostaglandins, endothlein, and nitric oxide,
• Excrete drugs and toxins from body fluids

Question 10

What hormones does the kidney help produce as a part of its endocrine involvement?

Answer 10

• renin for regulation of blood pressure
• erythropoietin for erythrocyte production
• activate Vitamin D for calcium and phosphate metabolism

Question 11

Summaries the RASS system

Answer 11

= initiates fluid balance.

Triggers: renal afferent arteriole pressure drops, or an decrease in serum sodium concentration is detected by the distal convoluted tubules.
- renin is released from the juxtaglomerular cells
- Renin is used to convert angiotensinogen to angiotensin I, which is then converted to Angiotensin II via the Angiotensin converting enzyme (ACE) produced in the lungs
- Angiotensin II is a potent vasoconstrictor, raising blood pressure. Angiotensin II also stimulates the release of aldosterone, which acts to increase water and sodium reabsorption in the kidneys to increase intravascular circulating volume. Figure 7 outlines the renin-angiotensin-aldosterone system.

Question 12

How does ADH influence fluid balance and why?

Answer 12

Antidiuretic hormone (ADH)
aka vasopressin
- produced in the hypothalamus and stored in the pituitary
- released by posterior pit gland
- released in response to
- hyperosmolarity/increased serum osmolality (increase in solute concentrations/decreased water concentration)
- decreased blood pressure
- volume depletion
- noxious stimuli
- hypovolaemia
- pyrexia
- medications
- emotional/physical stress
= ADH in the blood causes the distal convoluted tubules and the collecting ducts to become more permeable to water, increasing water reabsorption, reducing urine output, and improving overall circulating volume.

Summary
- Osmoreceptors (water) located in hypothalamus detecting serum osmolality levels greater than 285mOsm/kg
- ADH released and carried to nephrons
- Kidney distal tubules, connecting tubules and collecting ducts alter permeability to water by action of ‘aquaporins

Question 13

\What does aldosterone do and why?

Answer 13

= released by adrenal gland cortex and acts on distal tubules to reabsorb sodium from the tubular lumen into the circulation.
When sodium is retained so is water several factors stimulate the release of aldosterone including;
- Thypovolaemia,
- hyponatraemia
hyperkalemia
- stress.

Question 14

Explain Atrial Natriuretic Peptide Hormone and its effect

Answer 14

= secreted from the atria of the heart in response to hypernatremia, stimulation of stretch receptors due to increased volume and increased pressure on the heart.
- Acts by blocking Aldosterone and ADH production, initiating vasodilation and stimulating increased sodium and water excretion by the collecting ducts.

This produces diuresis, decreased cardiac workload and reduction in cardiac preload and after load.

Question 15

Where is potassium exchanged and in what way? What are some factors that affect absorption and secretion of potassium?

Answer 15

Potassium is reabsorbed from the filtrate by proximal tubules and secreted back into the filtrate in the distal tubules. It’s all about the filtrate!

1. Sodium deficit = potassium loss
2. Acidosis: Hydrogen into cell and potassium out to be excreted
3. Diuretics: Increased loss of potassium in the distal tubule
4. Insulin: Promotes movement if potassium into cell
5. Adrenaline: Enhances potassium resorption (this is not a typo!) from proximal tubule.

Question 16

Where is sodium exchanged and what does this result in?

Answer 16

Sodium balance regulated by kidneys, adrenal glands (aldosterone secretion) and posterior pituitary gland (ADH).
- Most reabsorption in distal tubule under the influence of aldosterone.
- When diuretics are administered, sodium absorption is inhibited and sodium is eliminated in the urine.
- This active process is regulated by site specific sodium transporters.

Question 17

Where is phosphorous exchanged and in what ways?

Answer 17

• 90% in plasma is filtered by glomerulus and 80% is reabsorbed by the proximal tubules.
• This resorption is increased when phosphorus levels are low.

Question 18

Where is chloride exchanged and in what ways?

Answer 18

• actively transported out of tubules into interstitium with sodium to help maintain the high tubular interstitial osmolality and the mechanism for concentrating the urine.

Question 19

Where is bicarbonate exchanged and in what ways?

Answer 19

• Reabsorption of bicarbonate takes place primarily from the proximal tubule into peritubular capillaries.
• Bicarbonate is also produced in the distal tubule and reabsorbed into the blood in response to acid-base balance need.
• Bicarbonate is a major ECF acid base buffer.
• More bicarbonate is reabsorbed when large numbers of hydrogen ions are present, and more bicarbonate is excreted when fewer hydrogen ions are present.

Question 20

What is normal serum pH?

Answer 20

7.35-7.45

Question 21

How do the kidneys maintain serum pH?

Answer 21

= a buffering process through altering reabsorption and secretions of acids (H+ ions) and bases (HCO3-) when changes to pH are detected.

carbonic acid- bicarbonate buffering system equation representation
CO2 + H20 ↔ H2CO3- ↔ H+ + HCO3-
- Normally, carbon dioxide is eliminated by the lungs, however, when it remains in the plasma it combines with water to form carbonic acid, a weak acid.
- Carbonic acid then dissociates to form hydrogen ions (an acid) and bicarbonate (a base). In order to maintain normal pH, the kidneys respond by increasing the secretion of H+ and the reabsorption of HCO3-.
- The renal response to changes in blood pH requires several hours to days to take effect.
- During acidosis kidney raises H+ secretion by active transport to combine with ammonia in the renal tube to produce ammonium which is unable to be reabsorbed
- Raised H+ excretion increases the reabsorption of sodium which increases HCO3- resorption
- During alkalosis the resorption of H+ ions is increased

Question 22

What do the kidneys remove as a part of their waste product removal role?

Answer 22

• By-products of protein metabolism:
  - Urea - End product of breakdown of protein, so volume influenced by amount of protein in diet. Urea is filtered in the glomerulus but can also be secreted and reabsorbed in the tubules. Is an indicator of renal function.
  - Creatinine - end product of metabolism. Exclusively excreted by kidneys, so indicator of kidney function. Creatinine is filtered in the glomerulus and a small amount is excreted in the tubules.
  - Uric acid
• Metabolic acids
• Bilirubin
• Medications/metabolites

Question 23

How do the kidneys regulate blood pressure?

Answer 23

RAAS and the stimulation of angiotensin 2 which
- increases blood pressure via vasoconstriction.
- stimulated adrenal cortex to release aldosterone and cause tubules to increase reabsorption fo sodium and water= increase volume and pressure.
- blood viscosity is modulated by this system

Question 24

What is the relationship between RASS and high blood pressure?

Answer 24

If the renin-angiotensin-aldosterone system is too active, blood pressure will be too high.

Many drugs interrupt different steps in this system to lower blood pressure.

These drugs are one of the main ways to control high blood pressure (hypertension), heart failure, kidney failure, and the harmful effects of diabetes.

Question 25

What is the kidney’s involvement in vit D activation?

Answer 25

• Kidneys convert Vitamin D from food sources into active form for use in the body by hydroxylation - calcitriol.
• Active Vitamin D (calcitriol) stimulates absorption of calcium by the intestine and resorption of calcium by the tubules.
• When kidneys fail, their ability to activate vitamin D is lost.
• Without the activated vitamin D to control calcium and phosphorus levels in the blood, PTH will try to overcompensate and go out of range. - PTH is secreted by the parathyroid glands that are located in the neck near the thyroid glands. When kidney failure occurs, the kidney is unable to convert Vitamin D to its active form, this results in poorly absorbed calcium, bone disease and other immunological issues.

Question 26

What is the kidney’s involvement in prostaglandin synthesis?

Answer 26

Kidneys produce 2 vasodilatory prostaglandins - PGE1 and PGI2.

Prostaglandins are produced in all nucleated cells.

Both vasodilators act on afferent arterioles to maintain blood flow and glomerular filtration and perfusion.

PGF2 - not produced by kidney, but acting on the kidney, contributes to vasoconstriction in times of volume depletion

Question 27

Define GFR

Answer 27

is related to renal blood flow and perfusion pressure in the glomerular capillaries. When blood pressure decreases, renal blood flow decreases and GFR decreases. The opposite occurs for an increase in blood pressure. Normal GFR is approximately 120-125 mL/min

Question 28

What mechanisms affect GFR?

Answer 28

A number of mechanisms maintain renal blood flow and GFR:
- renal autoregulation (vasoconstriction or vasodilation of renal artery)
- tubuloglomerular feedback (afferent arteriole vasoconstriction or vasodilation based on Na+ levels)
- sympathetic nervous system (decreased blood pressure detected by carotid sinus and baroreceptors of aortic arch leading to vasoconstriction afferent arterioles)
- Renin-Angiotensin-Aldosterone system

Question 29

What actually happens in glomerular filtration?

Answer 29

• Within the glomerulus, blood is filtered, to excrete waste, and form urine.
• Filtration occurs via a passive process.
• The layers of the glomerular filtration membrane lining the arterioles are ‘fenestrated’ which means they have small ‘holes’ or ‘windows’ through which solutes and small proteins can pass.
• Red and white blood cells, and large proteins, cannot pass through the fenestrations due to their size.
• Fluid and solutes are forced through these fenestrations by hydrostatic pressure (blood pressure). Opposing the hydrostatic pressure, and therefore impacting on filtration, are interstitial fluid hydrostatic pressure and oncotic pressure.
• Fluids and solutes that pass through the glomerular filtration membrane are known as filtrate. The filtrate contains electrolytes (e.g. sodium, chloride, potassium) and other molecules (e.g. creatinine, urea, glucose) in the same concentration as in plasma.
• Filtrate is collected in the Bowman’s capsule, then flow on through the renal tubules in the nephron to form urine. The renal tubules are responsible for the majority of the secretion of substances into, and the reabsorption of substances from, the filtrate, in order to form urine.
• Reabsorption may occur passively, down concentration gradients (such as water), or may be actively undertaken by specialised transport cells (includes transport of sodium, chloride, glucose and bicarbonate). Different substances are secreted and reabsorbed at various points along the proximal and distal convoluted tubules and loop of Henle.

The proximal convoluted tubule is where approximately 60-70% of filtered water and solutes are reabsorbed via diffusion, active transport (e.g. glucose), and osmosis (See Figure 5).
- Sodium is reabsorbed here by active transport using the sodium-potassium-ATP pump.
- Water and many electrolytes (potassium, chloride, calcium, phosphate) are co-transported with sodium (i.e., when sodium is reabsorbed, so are they).

In the loop of Henle, approximately 15% of water is reabsorbed.
- By the time the filtrate reaches the distal convoluted tubule, the majority of water and solute reabsorption has occurred.

The distal convoluted tubule and collecting duct are involved in adjusting the solute concentration and the amount of water, and this is mainly done via hormone control.
- The anti-diuretic hormone (ADH) causes water to be absorbed from the urinary filtrate so that more water returns to the blood.

Whilst the vast majority of substances which enter the urine do so as a result of glomerular filtration, some substances require active secretion via the tubular cells. These substances include acids and bases, food additives, drugs and chemicals present in the blood.

Question 30

Define glomerular filtration

Answer 30

= water and solutes smaller than proteins are forced though the capillary walls and pores of the glomerular capsule into the renal tubule.

Question 32

Define tubular reabsorption

Answer 32

Water, glucose, amino acids and needed iron are transported out of the filtrate into the tubule cells and then enter the capillary blood.

Question 33

Define tubular secretion

Answer 33

= creatine and drugs are removed from the peritubular blood and secreted by the tubule cells into the filtrate.

Question 34

What are some fun filtration facts?

Answer 34

• Entire blood volume is filtered 60 to 70 times a day
• 180 Litres of Filtrate produced/day!!
  Glomerular Filtrate Rate or amount of filtrate formed in the nephrons is 125mls/min
• 99% of filtrate reabsorbed only 1% excreted as urine which is 1 to 2 L of urine a day.