Block 8 - Renal physiology

Question 1

Give a simple explanation of how the kidney works to regulate extracellular fluid volume and its electrolyte concentrations (4 steps)

Answer 1

1) Blood enters the kidney through the renal artery

2) Blood is then filtered by the kidney and the filtrate is collected by the ureter

3) Filtered ‘clean’ blood leaves the kidney through the renal vein

4) Excess of electrolytes, toxic waste and water leaves the kidney in the form of urine through the ureter and fills up the bladder

Question 2

List the 4 basic renal processes

Answer 2

1 - Glomerular filtration
2 - Tubular reabsorbtion
3 - Tubular secretion
4 - Urine excretion

Question 3

Explain the process of glomerular filtration

Answer 3

Non-discriminant filtration of a protein-free plasma from the glomerulus into the Bowman’s capsule.

• Afferent arterile carrives the blood (plasma) to the capillaries of the glomerulus
• Pressure forces the plasma from capillaries into the bowman’s capsule (most of the proteins are removed by this filtration process)
• filtered plasma enters the proximal tubule

Question 4

Explain the process of tubular reabsorbiton

Answer 4

Selective movement of filtered substance from the tubular lumen into the peritubular capillaries

E.g.) Active Na+ reabsorbtion:
- occurs throughout tubule (except for descending limp of the loop of Henle)
- keeps intracellular Na+ low and builds high Na+ in the lateral space
- 80% of kidney energy requirement

99.5% of Na+ filtered is reabsorbed
- 67% through the proximal tubule
- 25% ascending loop of Henle
- 8% through distal tubule and collecting duct (can vary due to hormonal control

Question 5

Explain the process of tubular secretion

Answer 5

Selective movement of non-filtered substances from the peritubular capillaries into the tubular lumen

E.g.) Active K+ excretion: Na+K+ ATPase pump
- K+ flows through graduent to enter the tubular lumen through the luminal membrane (range of K+ channels)
- K+ follows the concentration gradient to exit the peritubular capillary and enter in the extracellular spcae

Question 6

Explain the process of urine exretion

Answer 6

Creation of the medulla verticle osmotic gradient

Question 7

What benefit does the nephron being surrounded by the peritubular capillary network have?

Answer 7

Allows for easy fluid transfer between the fluid inside the tubules and the blood within the peritubular capillaries

Question 8

Explain the process of renal reabsorbtion (transepithelial transport steps)

Answer 8

To be reabsorbed a substance needs to cross:
1 - The luminal membrane of the tubular cells
2 - The cytosol of the tubular cells
3 - Basolateral membrane of the tubular cells
4 - The interstitial fluid through diffusion
5 - Capillary wall to eneter the blood plasma

Question 9

What is the rate of glomerular filtration (GRF)?

Answer 9

125 ml/min
180L per day

80% of the plasma that enters the glomerulus is not filtered and leaves through the efferent arteriole

20% of the plasma that enters is filtered

123.75 ml is reabsorbed into the body to prevent death by dehydration (22mins to excrete all adult plasma volume if everything filtered was removed)

Question 10

Explain the hormonal modulation of Na+ reabsorbtion in the distal tubule and collecting ducts

Answer 10

Na+ reabsorbtion is subject to hormonal control and is inversely dependent on the total amount of Na+ in the body fluids

• too much Na+ = no reabsorbtion = excreted
• too little Na+ = most or all reabsorbed

Long-term control of arterial blood pressure depends on the renin-angiotensin-aldosterone system

Question 11

What role does the juxtaglomerular apparatus and where is it found?

Answer 11

The origin of the hormone renin

It is found where the distal tubule passes through the fork fomed by the afferent and effertent arterioles on the same nephron

Question 12

What functions do the granular cells in the juxtaglomerular have?

Answer 12

They secrete renin.

• Acts as intrarenal baroreceptors - if bp drops within the afferent arteriole then the granular cells will secrete more renin.
• They are also innervated by sympathetic nervous system. When systematic BP decreases, sympathetic activity increases and stimulates granular cells to secrete more renin.
• The macula densa senses [Na+] and [Cl-] passing thorugh the distal tubule. If the concs decrease then macula densa cells stimulate granular cells to secrete more renin.

Question 13

How is aldosterone formed in the RAA system (renin-angiotensin-aldosterone system)?

Answer 13

When renin (from kidneys) and angiotensinogen (from liver) interact in the bloodstream they form angiotensin 1.

Angiotensin 1 interacts with angiotensin-converting enzyme (from lungs) to form angiotensin II.

Angiotensin II stimulates the adrenal cortex to produce aldosterone.

Aldosterone acts on the kidney and controls arteriole blood pressure.

Question 14

How does aldosterone control arteriole blood pressure?

Answer 14

• Aldosterone increases Na+ reabsorbtion by the distal tubules and collecting ducts.
• Additional Na+K+ ATPase pumps form in the basolateral membrane.
• Additional Na+ channels (Enac) from in the luminal membrane of tubular cells.
• Cl- flows passively through different types of transporters to re-establish the charge equilibrium
• The increase of Na+ and Cl- in the bloodstream and tissues leading to extracellular fluid (ECF) rise as H2O follows to re-establish the isotonic equilibrium.

Question 15

Explain the hormonal control of arterial blood pressure and urine concentration

Answer 15

Angiotensin II increases levels of vasopressin/ ADH which causes an increase in H2O reabsorbtion by kidney tubules.

Leads to H2O conservation, affecting arterial bp and urine conc.

Question 16

How much urine is formed in a healthy hydration condition and bp?

What about excess water and high bp?
Dehydration and low bp?

Answer 16

Healthy:
1.25ml/min of isotonic urine, 300 mosm/l
Isotonic because there’s the same conc as solute conc in ECF

Over+high:
25ml/min, hypotonic urine at 100 mosm/l

Under+low:
0.3ml/min, hypertonic urine at 1200 mosm/l

mosm/l = milliosmoles per litre

Question 17

What role does the vertical osmotic gradient have?

Where is it found and what mediates it?

Answer 17

Enables the kidenys to produce urine concentrations ranging between 100 and 1200 mosm/l - either more or less dilute than the average EFC tonicity (300 mosm/l).

Found in the renal medulla and mediated by vasopressin (ADH) which increases the reabsorbtion of water.

Question 18

What 3 things does the control of urine concentration regulate?

Answer 18

• The level of hydration in the body
• Extracellular fluid (EFC) solute concentration
• Arterial blood pressure

Question 19

Explain how and where the medullary vertical osmotic gradient is created.

Answer 19

• Established by the juxtamedullary nephrons’ loops of Henle (very long, go deep into medulla)
• Ascending part of LoH is impermeable to water (active reabsorbtion of Na+), descending part is permeable to water (however no Na+, K+ or Cl- transport).

Question 20

Explain how the active reabsorbtion of Na+ occurs in the ascending limb of LoH.

Answer 20

Na+/K+ ATPase on the basolateral membrane of the tubular cells pump Na+ into the interstitial fluid (increasing osmolarity)

Na+/K+/Cl- co-transporter on the luminal membrane of tubular cells allow the ions to move from the tubule lumen into the cytosol of these cells (decreases osmolarity in the asc limb of LoH)

Cl- follows Na+ (via hCIC-Kb channels) to maintain the electrical neutrality of interstital fluid and further increasing osmolarity.

Question 21

What is the role of the vasa recta (peritubular capillaries) in the renal medulla?

Answer 21

Allows for:
- Gas exchange (O2/CO2) and nutrients
- Reabsorbtion of water and solutes

The capillary wall is permeable to ions and water allowing the blood to equillibrate its osmolarity with the interstitial fluid and LoH at every level, allowing reabsorbed water and ions back into the body.

This also aids the establishment and sustainability if the vertical osmotic gradient.

Question 22

Explain the mechanism of action of vasopressin (ADH): water reabsorbtion.

Answer 22

ADH reaches the kidneys via the peritubular capillaries - it binds to vasopressin receptors located on the basolateral membrane of the distal tubular and collecting duct cells.

ADH induces the relocation of additional aquaporins (water channels) to the apical membrane of the tubular cells.

Additional aquaporins increase the permeability of the luminal membrane to H2O and allow the entry of more water into tubular cells and interstitial fluid in order to reach isotonicity between the tubular fluid (urine) and the interstital fluid and plasma.

• Tubular fluid concentration is increased as water is absorbed into the tubular cells and body.

Question 23

How many types of aquaporins are expressed in the kidney?

Answer 23

7 types.

AQP 1, 2, 3, 4, 6, 7 and 11.

Question 24

Where is vasopressin produced and secreted?

Answer 24

Vasopressin is produced in the hypothalmus by secreted by the posterior pituitary.

Question 25

Explain the homeostatic control of urine concentration.

Answer 25

Healthy hydration:
Some ADH secreted
- distal tubules and collecting ducts are partially permeable to H2O

Excess water:
No ADH secreted
- distal tubules and collecting ducts are impermeable to H2O

Dehydration:
A lot of ADH secreted
- distal tubules and collecting ducts become highly permeable to H2O

Question 26

What is nephrogenic diabetes insipidus (NDI)?

Answer 26

A genetic disorder in which the distal tubules and colecting ducts of the kidneys do not show a normal increase in water permeability in response to vasopressin.

Vasopressin is produced by unable to induce H2O reabsorbtion due to defective vasopressin receptors or deficient aquaporins

Leads to excessive secretion of dilute urine (polyuria), dehydration and thirst.

• Unrelated to blood-sugar level
• Nephrogenic - orginates in the kidney
  Insipidus - latin for ‘tasteless’ = weak urine conc

Question 27

How does alcohol consumption affect hydration?

Answer 27

Alcohol consumption inhibits vasopressin secretion in the posterior pituitary leading to diluted urine and the urge to urinate.

This leads to dehydration and thirst.

Question 28

How do human nephrons and those of desert animals differ?

Answer 28

In order to keep as much H2O desert animals have:
- Longer nephrons
- Nephron that goes deeper into the medulla
- Greater osmotic gradient
- Urine is more concentrated
- More H2O is preserved by the body

Question 29

What is the process of micturition?

Answer 29

Micturition is the excretion of urine.

Urine, moves out of the collecting ducts into the renal pelvis, it then leaves the kidney through the ureter and enters the bladder where it is stored until excretion.

Question 30

How does the reflex control of micturition work?

Answer 30

Urination:
1) Bladder fills activating the stretch receptors
2) Stimulates the parasympathetic nerve and inhibits action potential from the motor neuron to the external spincter.
3) External urethral sphincter opens when motor neuron is inhibited.
4) Parasympathetic nerve stimulates bladder to contract and internal urethral spincter mechanically opens.

Question 31

How does the voluntary control of micturition work?

Answer 31

No urination:
1) Cerebral cortex stimulates action potential from the motor neuron to the external sphincter
2) External sphincter remains closed when motor neuron is stimulated

Question 32

What is chronic kidney disease (CDK)?

Answer 32

Chronic disease - lasting 3 months or more and cannot be prevented by vaccines, cured by medication or disappear.

Progressive and irresversible loss of kidney structures.

Many types:
- genetic
- polycystic kidney disease
- cancer

Can be secondary to other disease e.g. hypertension or diabetes.

Question 33

Explain the 5 stages of kidney disease.

Answer 33

% = of normal kidney function

Stage 1: 90% or more
Stage 2: 60-89%
Stage 3: 30-59%
- No specific symptoms but kidney function may decline.

Stage 4: 25-29%
- Kidney function is very low and treatment for kidney failure may be needed soon

Stage 5: <15%
- Kidneys can no longer keep up with removing waste products and extra water. Kidney failure.
- No cure but treatment available.

Question 34

What are the 8 main symptoms of end-stage renal disease?

Answer 34

• dehydration/ thirst
• electrolyte imbalance
• acid-base disturbances
• anorexia, nausea (accumulation of waste products)
• anaemia due to decrease in erythropoietin secretion, bleeding
• hypertension and oedema due to RAA system activation (inc in plasma vol)
• weakened muscles and bones due to calcium and other mineral imbalance (impaired activation of vitamin D)
• uremic encephalopathy (accumulation of ammonia and nitrogenous waste leading to delirium, seizure and coma)

Question 35

How is CDK treated?

Answer 35

Kidney transplant:
- optimal treatment, however not many available

Dialysis
- not a cure but prolongs life while waiting transplant
- uses semipermeable membrane to allow small solutes to exchange freelu netween the blood and a dialysing solution (eliminates contaminants from blood)

2 types of dialysis:
- haemodialysis (haemodialysis system/ artifical kidney)
- peritoneal dialysis (uses peritoneum as dialysis membrane)

Question 36

What are the types of diabetes related to blood-sugar levels?

Answer 36

Type 1 diabetes:
- lifelong autoimmune disease where the immune system attacks and destorys the pancreatic cells which normally produce insulin. (8%)
- High blood glucose.

Type 2 diabetes:
- Lifelong metabolic disease where pancreas can’t produce enough insulin or insulin doesn’t work properly (90%)
- High blood glucose

Gestational diabetes:
-The hormones produced during pregnancy and foetus demand on the mother’s body make it difficult for the body to use or produce insulin properly
- High blood glucose
- Usually disappears after giving birth

Other types:
- monogenic diabetes
- cystic-fibrosis related diabetes
- caused by rare syndromes
- surgery, hormonal disregualtion and medication related (incl steroids and antipsychotics)
- Maturity Onset Diabetes of the Young (MODY)
- Neonatal diabetes
- Wolfram and Alström syndromes
- Latent Autoimmunse Diabetes in Adults (LADA)

Question 37

What is central diabetes insipidus (neurogenic diabetes insipidus)?

Answer 37

Failure of production of vasopressin by the hypothalamus or the failure of excretion by the pituitary gland.

Leads to excessive excretion of dilute urine (polyuria), dehydration and thirst.

• Not related to blood-sugar levels
• Can be aquired or genetic.