Structure and Function of the Kidney (1-2)

Question 1

What does the renal system consist of?

Answer 1

Kidneys, ureters and urethra

Question 2

What is the function of the renal system?

Answer 2

Contributes to homeostasis by controlling →
1. Blood ionic composition
2. Blood pH
3. Blood volume
4. Blood pressure
5. Blood osmolarity
6. Excretion of waste
7. Hormone production
8. Glucose levels

Question 3

What are the signs/symptoms of hypovolaemia (dehydration) and hypervolemia (fluid overload)?

Answer 3

Hypovolaemia:
Symptoms → thirst, dizziness on standing, confusion
Signs → low JVP, postural hypotension, weight loss, dry mucous membranes, reduced skin turgor, reduced urine output

Hypervolaemia:
Symptoms → ankle swelling, breathlessness
Signs → raised JVP, oedema, weight gain, hypertension

Question 4

How do the kidneys regulate fluid balance?

Answer 4

Kidneys play a major role in body fluid homeostasis → regulate both volume and composition

→ alter volume and composition of the plasma influencing other fluid compartments
→ mainly by changing extracellular sodium conc. and water - in turn controls blood pressure

Question 5

What is osmolarity?

Answer 5

The measurement of solute concentration or osmotically active solutes
→ units: osmoles (osmol/L)

1 osmole = 1 mole of any fully dissociated substance dissolved in water

high osmolarity = high conc = high osmotic pressure

Question 6

What is osmotic pressure?

Answer 6

The pressure which needs to be applied to the solution to prevent an inward movement of fluid across a semi permeable membrane

high osmolarity = high osmotic pressure (strong inward pull of fluid)

Question 7

What is the oncotic and hydrostatic pressure?

Answer 7

Oncotic → the osmotic pressure exerted by the proteins in the blood plasma or filtrate which attracts/pulls water into that compartment
→ to filter fluid out need to overcome oncotic pressure

Hydrostatic → the force exerted by a fluid against a capillary wall (pushes fluid out)

Question 8

What occurs if hydrostatic pressure (Pc) > osmotic pressure?

Answer 8

Fluid will leave the capillary promoting filtration of the plasma
→ large diameter of afferent arteriole entering the capillary bed (e.g. glomerulus), small diameter leaving
→ the high hydrostatic pressure (promotes filtration), as a result of different diameters, overcomes the inward pull of fluid due to osmotic pressure

Question 9

What occurs if hydrostatic pressure (Pc) < osmotic pressure?

Answer 9

Fluid leaving the capillary will be greatly reduced inhibiting filtration of the plasma
→ medium diameter of afferent arteriole entering capillary bed (e.g. glomerulus), medium diameter leaving
→ the low hydrostatic pressure as a result of similar diameters only just overcomes the inward pull due to osmotic pressure

Question 10

What is ultrafiltration and selective reabsorption?

Answer 10

Ultrafiltration = blood filtered out of the glomerulus at the Bowman’s capsule to form filtrate
→ non-specific, under high pressure

Selective reabsorption = usable materials reabsorbed in convoluted tubules (proximal and distal)

Question 11

How is blood supplied to the kidney nephrons?

Answer 11

Renal arteries takes blood to nephron
renal artery → segmental artery → interloper artery → arcuate artery → interlobular artery → afferent arteriole → glomerulus → efferent arteriole

(peritubular capillary)

Renal veins take blood away
interlobular vein → arcuate vein → interlobar vein → renal vein

Question 12

What is the vasa recta?

Answer 12

Capillary network that surround the nephew supplying blood to the medulla
→ forms parallel hairpin loop to the loop of Henle
→ maintains counter-current multiplier

Question 13

What is a nephron?

Answer 13

The functional unit of the kidney, it consists of:
- Renal corpuscle → blood filtering component
→ Bowman’s capsule, glomerulus
- Renal tubule → lead away from the glomerulus
→ proximal convoluted tubule, loop of Henle, distal convoluted tubule

Many nephrons collect to one collecting duct

Question 14

What are the 2 types of nephron?

Answer 14

Cortical nephron (85%) → short loop of Henle

Juxtamedullary nephron (15%) → long loop of Henle, involved in producing highly conc. urine
→ long loop produces large amount of reabsorption of fluid

Question 15

What is the overall function of nephrons?

Answer 15

1. Filtration → high hydrostatic pressure pushes fluid out of capillary (glomerulus) into Bowman’s capsule and PCT
2. Tubular reabsorption → 99% of water and many solutes reabsorbed back into blood
   → via passive and active processes (glucose, aa, urea, ions, Na+, K+, Ca2+, HCO3-, HPO42-)
3. Tubular secretion → renal tubule and duct cells secrete wastes, drugs, excess ions out of blood into filtrate
4. Urine excretion → out of the collecting duct - calyx - ureter

Question 16

How does blood move through the renal corpuscle?

Answer 16

Blood enters via the afferent arteriole into the glomerulus (tuft of capillaries) and leaves via the efferent arteriole

Question 17

What are podocytes?

Answer 17

Inner surface cells of the visceral layer of the Bowman’s capsule
→ have extensions called pedicels that wrap around the blood vessels of the glomerulus
→ the gaps are important for filtration

Between the podocytes and the glomerulus is the basement membrane (glycoprotein matrix) - which filters blood

Question 18

What is the juxtaglomerular apparatus?

Answer 18

JGA consists of:
→ macula densa cells (small part of the distal tubule located beside the glomerulus)
→ extraglomerular mesangial cells
→ granular cells of the afferent arteriole

Involved in feedback control of renal blood flow and glomerular filtration rate
→ JG granular cells secrete enzyme renin in response to falls in extracellular volume/low sodium
→ falls in ECF volume detected by baroreceptors around the body
→ aim of the response is to increase sodium reabsorption and therefore water reabsorption

Question 19

What is the process of glomerular filtration?

Answer 19

1. Fenestrated (pores) glomerular capillary endothelium allows everything but RBC and platelets through
   → fenestrations 0.07-0.1um diameter
2. Basal lamina of glomerulus prevents filtration of larger proteins
   → basal membrane - collagen and -ve charged proteins - repels -ve molecules
3. Spaces between pedicels (of the visceral layer of the Bowman’s capsule) prevents filtration of medium proteins
   → water, glucose, vitamins, ammonia, urea, ions, small plasma proteins, albumin pass through

Glomerular filtrate ends up in capsular (Bowman’s) space then heads to the proximal convoluted tubule

Question 20

Are the capillaries of the glomerulus leaky?

Answer 20

Yes - glomerulus capillaries have fenestrations (pores)
→ allows for fluid to be pushed out by hydrostatic pressure

Question 21

Why does filtration happen to a greater extent in the renal corpuscle?

Answer 21

• Large surface area of the glomerular capillaries - regulated by contractile properties of mesangial cells
• Endothelial capillary membrane is thin and and fenestrated ~50X leakier than other capillaries
• Blood pressure is higher owing to the differences in diameter of afferent and efferent arterioles (big hydrostatic pressure forcing fluid out)

Question 22

What is the net filtration pressure?

Answer 22

NFP = the total pressure that promotes filtration

NFP = GBHP - CHP - BCOP

GBHP → glomerular blood hydrostatic pressure (PGC)
CHP → capsular hydrostatic pressure (PBC)
BCOP → blood colloid osmotic pressure

Question 23

What is the glomerular filtration rate?

Answer 23

GFR = amount of filtrate formed by all the nephrons (renal corpuscles) of both kidneys per minute

→ dependent on the difference between the hydrostatic pressures of the Glomerular capillary and Bowman’s capsule (PGC and PBC) and the oncotic pressure of the capillary and capsule (πGC and πBC)
GFR = (HPGC – HPBC) – (πGC - πBC )

→ also affected by the permeability of the filtration barrier and filtration surface area = filtration coefficient Kf
GFR = Kf (HPGC – HPBC) – (πGC - πBC )

Question 24

What are the 3 mechanisms that control glomerular filtration rate?

Answer 24

1. Renal auto regulation (1 - myogenic, 2 - tubuloglomerula feedback) → intrinsic
2. Neuronal regulation → extrinsic
3. Hormal regulation → extrinsic
   → GFR needs to be controlled and maintained at correct level

Work in 2 different ways:
1. Adjustment of blood flow into and out of the glomerulus
2. Alteration of glomerular capillary surface area (mechanical)

Question 25

How is renal auto regulation done by myogenic mechanisms?

Answer 25

Control of GFR by muscle within the arteries → increase or decrease pressure - change diameter 1. Increased BP stretches the walls of afferent arterioles 2. Activates the juxtaglomerular apparatus - smooth muscle fibres contract 3. Narrowing of the afferent arteriole lumen 4. Decreased blood flow and GFR (opposite happens in response to low blood pressure)

Question 26

How is renal auto regulation done by tubuloglomerular feedback?

Answer 26

Negative feedback regulation via Macula densa cells - slower mechanism 1. Increased BP - increase in hydrostatic pressure so more fluid being pushed out of capillary - increased GFR 2. Macula densa cells of JGA detect increased delivery (decreased reabsorption) of Na+, Cl- and water 3. JGA decreased secretion of NO (vasodilator) 4. Afferent arteriole constricts - decreases blood flow through glomerulus → decreases GFR - return to homeostasis

Question 27

What substance should be fully reabsorbed by the kidneys?

Answer 27

Glucose → should be no glucose in the urine

Question 28

How is water reabsorbed in the kidneys?

Answer 28

Most water is reabsorbed in proximal convoluted tubule (65%) and Loop of Henle (20%) → all water movement is passive - no energy, no transporters → water is polar so can't move through membranes - has to go through channels called aquaporins (controlled by ADH) → moves down osmotic gradients out of tubules through aquaporins

Question 29

How is concentrated urine produced by the collecting ducts?

Answer 29

1. Insertion of water channels (aquaporins) regulated by ADH 2. An osmotic gradient - generated by the countercurrent system in the loop of Henle

Question 30

What do substances moving out of tubules (reabsorption) have to pass through?

Answer 30

tubule lumen → membrane → cytosol → membrane → interstitial fluid → membrane → capillary

Question 31

How is glucose reabsorbed in the PCT?

Answer 31

Sodium glucose transporters (SGLTs) → con-transported with Na+ at the luminal membrane by a Na+/glucose co-transporter → diffuses from the cell into interstitial fluid into the peritubular capillaries

Question 32

What is the renal threshold for glucose?

Answer 32

The plasma glucose conc. above which glucoseuria occurs (glucose in urine) ~300mg/100ml → glucose transporters can be saturated - can't move glucose quick enough - leads to excretion

Question 33

How are sodium ions reabsorbed?

Answer 33

Na+ is co-transported with H+ → Na+ reabsorbed, H+ secreted → helps to maintain pH levels Also via Na+ K+ ATP pump

Question 34

What is reabsorbed at the distal part of the PCT?

Answer 34

Certain ions (Cl-, K+, Ca2+, Mg2+) and urea are passively reabsorbed

Question 35

How does reabsorption occur in the loop of Henle?

Answer 35

Descending limb → permeable to water Ascending limb → impermeable to water → cells have Na+ - K+ - 2CL- symporters in the apical membrane

Question 36

What is reabsorbed in the DCT and CD?

Answer 36

The amount of water and solute reabsorption in the late DCT and CD varies depending on the body's needs → water is heavily influences by ADH

Question 37

How is ADH release controlled?

Answer 37

ADH (vasopressin) release increases water reabsorption Peripheral volume receptors: low pressure sensors in atria and pulmonary vasculature, high pressure sensors in carotid sinuses and aortic arch, stretch receptors in afferent arterioles → detect a decrease in pressure/stretch - cause increase of ADH made by hypothalamus

Question 38

What is ADH?

Answer 38

Antidiuretic hormone → made by supraoptic and paraventricular nuclei of hypothalamus, released by posterior pituitary, acts on kidney → short half-life = flexible system Functions: 1. Reduces water excretion (increase blood vol.) 2. Stimulate vasoconstriction (keep enough blood going to organs)

Question 39

What is the minimum volume of urine production?

Answer 39

~500mL/day → obligate urine volume required to remove waste products ~600mOsm/day osmotic strength of plasma ~300mOsm/L → osmotic gradient needs to reach ~1200mOsm/L in the loop of Henle to allow reabsorption to pass 300

Question 40

How is the counter current multiplier produced in the loop of Henle?

Answer 40

Descending limb → permeable to water Ascending limb → impermeable to water → Na+ and Cl- are transported by symporters in the thick ascending limb - concentrated medulla interstitial fluid Continual movement of fluid through the tubules means there is a constant build-up of ions - forming an osmotic gradient from 300-1200mOsm/L Vas recta network around the loop of Henle flows in the opposite direction

Question 41

How does counter current multiplication work?

Answer 41

Active movement of Na+ (and other solutes) out of the thick ascending limb into interstitial fluid → makes fluid in upper tubules more dilute → increases conc. interstitial fluid The increase in osmolarity in the middle interstitial fluid pulls water out of the descending limb → concentrates lower part of tubules Builds osmotic gradient

Question 42

How is dilute urine formed?

Answer 42

Low reabsorption of water The ascending limb is relatively impermeable to water → pumps move solutes out of tubule leaving behind dilute tubular fluid - dilute urine excreted

Question 43

How is concentrated urine formed?

Answer 43

The distal and collecting tubules are permeable to water in presence of ADH → water will move out so their is osmotic equilibrium with surrounding interstitial → osmolarity of medullary interstitum ~1200mOsm/L created by Juxtamedullary nephron → concentrated urine excreted

Question 44

What is the renin-angiotensin-aldosterone system?

Answer 44

When blood volume and BP is low walls of the afferent arteriole are less stretched → juxtaglomerular cells secrete enzyme renin (breaks down angiotensin) → produces angiotensin II (potent vasoconstrictor) → vasoconstriction of afferent and efferent arterioles - lower GFR → increases reabsorption of Na+, Cl- and water by activating Na+/H+ anti porters → stimulate the adrenal cortex to release aldosterone - reabsorption of water - increasing blood volume and BP (draw diagram for revision)

Question 45

How are ACE inhibitors used pharmacologically?

Answer 45

ACE (angiotensin converting enzyme produced by renal and lung epithelia) inhibitors block angiotensin → hypertension drugs → end in pril e.g. ramipril, knalapril, lisinopril