Module 4: Renal System and Ageing

Question 1

Functions of Kidneys

Answer 1

• Regulates the ECF
• ECF volume: water and sodium balance
• Electrolyte composition
• Osmolarity: 300 mOsm
• Acid/base balance
• Waste disposal (e.g. urea or foreign compounds)
• Hormone production
• Urine composition varies as the kidneys maintain homeostasis

Question 2

Structure of Kidneys

Answer 2

• Outer cortex
• Inner medulla (renal pyramids)
• Urine drains from renal pyramids into renal pelvis
• Urine leaves via the ureter
• Urine is produced in the nephrons

Question 3

Function and Structure of Nephron

Answer 3

= functional units of the kidneys

• Three components of the nephron:
  1. Renal corpuscle
  2. Renal tubule
  3. Collecting duct/system
• Renal corpuscle is the glomerulus and Bowman’s capsule

Question 4

Two Types of Nephrons

Answer 4

1. Cortical Nephrons
   - 80%
   - Short loop of Henle
   - Mostly in cortex
2. Juxtamedullary Nephrons
   - 20%
   - Long loop of Henle
   - Dips deep into medulla

Question 5

How Urine is made

Answer 5

1. Glomerular filtration (GF)
2. Tubular reabsorption (TR)
3. Tubular Secretion (TS)

GF occurs first
TR and TS occur simultaneously

Question 6

Glomerular Membrane

Answer 6

• Filtrate must pass through three layers of glomerular membrane:
  1. Glomerular capillary wall
  2. Basement membrane
  3. Podocyte filtration slits

1. Glomerular Capillary Wall
   - Has fenestrations (pores)
   - Allows passage of most plasma components except large proteins and cells
2. Basement Membrane
   - Gel like zone
   - Physical barrier: proteins can’t fit through
   - Electrical barrier: negative charge repels proteins
3. Podocyte Filtration Slits
   - Capillaries lined with podocytes (cells with long foot processes)
   - Adjacent podocytes interlace
   - Spaces between processes called filtration slits

Question 7

Function of Glomerulus

Answer 7

= Filtrate is similar to blood plasma and contains water, electrolytes and glucose.
In healthy people, filtrate does not contain much proteins. To produce filtrate, blood plasma needs to pass through the capillary wall, basement membrane and filtration slit

Question 8

Filtration Force: Glomerular Hydrostatic Pressure (GHP)

Answer 8

• Pressure of blood inside the glomerular capillaries
• Efferent arteriole has a smaller radius than afferent arteriole = high pressure
• 50 mmHg
• Favours filtration

Question 9

Filtration Force: Blood Colloid Osmotic Pressure (BCOP)

Answer 9

• Plasma proteins suck in glomerular capillaries
• Osmolarity is greater inside the capillaries than Bowman’s capsule
• Pulls fluid back into capillaries
• Opposes filtration

Question 10

Filtration Force: Capsular Hydrostatic Pressure (CsHP)

Answer 10

• Pressure of fluid inside Bowman’s capsule

- Opposes filtration

Question 11

Transepithelial Transport

Answer 11

• Tight junctions between tubular cells prevents substances from moving between cells
• Five barriers must be crossed during reabsorption:
  1. Luminal membrane of tubular cell
  2. Cytosol of tubular ell
  3. Basolateral membrane of tubular cell
  4. Interstitial fluid
  5. Capillary wall

Question 12

Process of Water Reabsorption

Answer 12

• Passive process
• Water reabsorption is osmotically linked to sodium reabsorption
• EXCEPTION: water reabsorption is hormonally controlled in distal tubule and collecting duct

Question 13

Aquaporins

Answer 13

Proximal Tubule
- In the proximal tubule, aquaporins are permanently inserted in the tubular cell membrane. As sodium is reabsorbed, water follows

Distal Tubule & Collecting Duct
- The water permeability of the distal tubule and collecting duct is controlled by vasopressin-dependent insertion of aquaporins in the luminal membrane

Question 14

Vasopressin Action

Answer 14

1. Blood-borne vasopressin binds with its receptor sites on the basolateral membrane of a principal cell in the distal or collecting tubule
2. This binding activates the cyclic AMP (cAMP) second messenger system within the cell
3. cAMP increases the opposite luminal membrane’s permeability to water by promoting the insertion of AQP-2 water channels into the membrane. This membrane is impermeable to water in the absence of vasopressin
4. Water enters the tubular cell from the tubular lumen through the inserted water channels
5. Water exits the cell through a different water channel (either AQP-3 or AQP-4) permanently positioned at the basolateral border and then enters the blood, in this way being absorbed

Question 15

Location of Osmotic Gradient

Answer 15

= Renal Medulla

Question 16

How does Osmotic Gradient work?

Answer 16

• Interstitial fluid in medulla becomes more concentrated towards the renal pelvis
• Gradient allows selective reabsorption of water in the distal tubule and collecting duct as the filtrate moves towards the renal pelvis

Question 17

Loop of Henle

Answer 17

• Plays an important role in establishing and maintaining the osmotic gradient in the renal medulla
• The juxtamedullary nephrons span the depth of the medulla and control the osmotic gradient
• Descending limb:
• High permeable to water (lots of aquaporins)
• Does not reabsorb sodium
• Ascending limb:
• Actively reabsorbs NaCl
• Impermeable to water (no aquaporins)
• Different reabsorption capabilities of the descending and ascending limbs allow the gradient to be formed
• The filtrate equilibrates with the medullary interstitial fluid in the descending loop of Henle as water leaves the tubule through aquaporins
• The filtrate concentration decreases in the ascending limb of the loop of Henle as sodium and chlorine are pumped out of the filtrate
• Filtrate leaving the loop of Henle has a lower concentration than interstitial fluid (100 mOsm)

Question 18

Over-Hydration

Answer 18

= No further reabsorption of water occurs in the distal tubule or collecting duct if vasopressin is absent

Question 19

De-Hydration

Answer 19

= Release of vasopressin (ADH) causes the insertion of aquaporins and reabsorption of water in the distal tubule and collecting duct

Question 20

Location of Sodium Reabsorption

Answer 20

• Nearly all sodium is reabsorbed from the filtrate

- It is reabsorbed along the length of the tubule and plays different role at each site

Question 21

Mechanism of Sodium Reabsorption

Answer 21

1. Sodium transport across the basolateral membrane is active (Na/K pump) and produces a sodium concentration gradient (low in cell, high in interstitial fluid)
2. Transport across the luminal membrane is passive and down the concentration gradient

Question 22

Hormonal Control

Answer 22

• 8% of sodium reabsorption is hormonally controlled
• Distal convoluted tubule and collecting duct
• RAAS
• RAAS is triggered by:
• Decreased NaCl in plasma
• Decrease blood pressure/volume
• Reabsorption of sodium through RAAS = reabsorption of water = increase blood pressure/volume

Question 23

Activation of the RAAS

Answer 23

• Granular (juxtaglomerular) cells release renin in response to a decrease in NaCl, plasma volume or blood pressure (enzymatic hormone)
• Three triggers for renin release:

1. Granular Cells are baroreceptors
   - Detect a drop in blood pressure in the afferent arteriole
2. Macula Densa cells detect a fall in NaCl in the distal tubule
   - Stimulate granular cells to release renin
3. Sympathetic activation of granular cells
   - Decrease blood pressure stimulates baroreceptor reflex

Question 24

RAAS Process

Answer 24

1. Granular cells secrete renin
2. Renin activates angiotensinogen into angiotensin 1
   - Angiotensinogen is a plasma protein (high concentration but inactive)
3. In lungs; angiotensin 1 converted into angiotensin 2 by angiotensin-converting enzyme (ACE)
4. Angiotensin 2 triggers release of aldosterone (hormone) from adrenal cortex
5. Aldosterone stimulates sodium reabsorption from distal tubule and collecting duct

*Sodium reabsorption “pulls” more water into the ECF (more salt and water in blood)

Question 25

Tubular Secretion

Answer 25

- Transfer of substances from the capillaries into the tubule - Allows the kidneys to selectively transfer substances that are too concentrated in the blood - Most important secretory systems are for: * Hydrogen = important in regulating acid-base balance * Potassium = keeps plasma potassium concentration at appropriate level to maintain normal membrane excitability in muscles and nerves * Organic ions = accomplish more efficient elimination of foreign organic compounds from the body

Question 26

Draw Renal Response to Haemorrhage

Answer 26

** See notebook for diagram

Question 27

Micturition Reflex

Answer 27

- Micturition reflex is involuntary and controlled at the spinal cord - Filling of the bladder stimulates stretch receptors - Triggers parasympathetic stimulation of the bladder muscle (contraction) - Internal sphincter opens - Micturition reflex inhibits motor neuron innervating the external urethral sphincter - Voluntary signals from cerebral cortex over-rides inhibition of motor neurons

Question 28

Function of Urinary System

Answer 28

= Urine formation and carry urine

Question 29

Innervation of Urinary System

Answer 29

- Parasympathetic (S2-4) - Sympathetic (T12 - L2) - Sympathetic (bladder neck) - Somatic (S2-4) Pudendal nerve

Question 30

Incontinence

Answer 30

- Involuntary loss of urine or stool in sufficient amount or frequency to constitute a social and/or health problem - A heterogenous condition that ranges in severity from dribbling small amounts of urine to continuous urinary incontinence

Question 31

Risk Factors of Incontinence

Answer 31

- Older age - Female - Pregnancy - Childbirth - Benign prostate hyperplasia and prostate cancer - Type 2 diabetes - Neurological disorders (e.g. stroke, PD) - Dementia - Possibly menopause

Question 32

Stress Incontinence

Answer 32

- Leaking of small amounts of urine due to pressure on the bladder during certain activities (i.e. coughing, lifting) - Relaxed pelvic floor - Increased abdominal pressure

Question 33

Urge Incontinence

Answer 33

- Involuntary urination is proceeded by feelings of urgency - Bladder muscle becomes overactive > involuntary contractions during filling - Bladder oversensitivity from infection or neurological disorders

Question 34

Overflow Incontinence

Answer 34

- Bladder does not completely empty and becomes distended - Increased pressure overcomes sphincter control - Urethral blockage - Bladder unable to empty properly

Question 35

Functional Incontinence

Answer 35

- Lack of recognition of need to urinate or inability to get to the toilet - Causes: dementia, mobility issues, eyesight issues

Question 36

Lifestyle and Behavioural Interventions as Treatment for Urinary Incontinence

Answer 36

- Weight loss - Reduction of caffeine and alcohol intake - Kegel exercise - Bladder training - Timed voiding

Question 37

Pelvic Floor Exercises as Treatment for Urinary Incontinence

Answer 37

- Use right muscle and right technique - Set exercise routine - Maintain routine

Question 38

Bladder Training as Treatment for Urinary Incontinence

Answer 38

- Behavioural intervention to re-establish bladder control in adults - Program takes 3-6 months or more

Question 39

Pharmacotherapy as Treatment for Urinary Incontinence

Answer 39

- Anticholinergics: relaxes detrusor muscle - Alpha - Adrenergic Agonists: increases tone of internal sphincter - Alpha - Adrenergic Blockers: relaxes the internal sphincter - 5-alpha-reductase inhibitors: reduces sizeof prostate

Question 40

Surgery as Treatment for Urinary Incontinence

Answer 40

Slings - Provide support to the urethra and closure at times of exertions - Used for treatment of stress incontinence Suspension Procedures - Bladder and urethra are elevated and sutured to the pelvic bone Surgery-Bulking Agents - Injected into tissue surrounding the urethra to keep the urethra closed