Module 4: Renal System and Ageing Flashcards
Functions of Kidneys
- 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
Structure of Kidneys
- 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
Function and Structure of Nephron
= 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
Two Types of Nephrons
- Cortical Nephrons
- 80%
- Short loop of Henle
- Mostly in cortex - Juxtamedullary Nephrons
- 20%
- Long loop of Henle
- Dips deep into medulla
How Urine is made
- Glomerular filtration (GF)
- Tubular reabsorption (TR)
- Tubular Secretion (TS)
GF occurs first
TR and TS occur simultaneously
Glomerular Membrane
- Filtrate must pass through three layers of glomerular membrane:
1. Glomerular capillary wall
2. Basement membrane
3. Podocyte filtration slits
- Glomerular Capillary Wall
- Has fenestrations (pores)
- Allows passage of most plasma components except large proteins and cells - Basement Membrane
- Gel like zone
- Physical barrier: proteins can’t fit through
- Electrical barrier: negative charge repels proteins - Podocyte Filtration Slits
- Capillaries lined with podocytes (cells with long foot processes)
- Adjacent podocytes interlace
- Spaces between processes called filtration slits
Function of Glomerulus
= 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
Filtration Force: Glomerular Hydrostatic Pressure (GHP)
- Pressure of blood inside the glomerular capillaries
- Efferent arteriole has a smaller radius than afferent arteriole = high pressure
- 50 mmHg
- Favours filtration
Filtration Force: Blood Colloid Osmotic Pressure (BCOP)
- Plasma proteins suck in glomerular capillaries
- Osmolarity is greater inside the capillaries than Bowman’s capsule
- Pulls fluid back into capillaries
- Opposes filtration
Filtration Force: Capsular Hydrostatic Pressure (CsHP)
- Pressure of fluid inside Bowman’s capsule
- Opposes filtration
Transepithelial Transport
- 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
Process of Water Reabsorption
- Passive process
- Water reabsorption is osmotically linked to sodium reabsorption
- EXCEPTION: water reabsorption is hormonally controlled in distal tubule and collecting duct
Aquaporins
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
Vasopressin Action
- Blood-borne vasopressin binds with its receptor sites on the basolateral membrane of a principal cell in the distal or collecting tubule
- This binding activates the cyclic AMP (cAMP) second messenger system within the cell
- 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
- Water enters the tubular cell from the tubular lumen through the inserted water channels
- 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
Location of Osmotic Gradient
= Renal Medulla
How does Osmotic Gradient work?
- 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
Loop of Henle
- 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)
Over-Hydration
= No further reabsorption of water occurs in the distal tubule or collecting duct if vasopressin is absent
De-Hydration
= Release of vasopressin (ADH) causes the insertion of aquaporins and reabsorption of water in the distal tubule and collecting duct
Location of Sodium Reabsorption
- Nearly all sodium is reabsorbed from the filtrate
- It is reabsorbed along the length of the tubule and plays different role at each site
Mechanism of Sodium Reabsorption
- Sodium transport across the basolateral membrane is active (Na/K pump) and produces a sodium concentration gradient (low in cell, high in interstitial fluid)
- Transport across the luminal membrane is passive and down the concentration gradient
Hormonal Control
- 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
Activation of the RAAS
- Granular (juxtaglomerular) cells release renin in response to a decrease in NaCl, plasma volume or blood pressure (enzymatic hormone)
- Three triggers for renin release:
- Granular Cells are baroreceptors
- Detect a drop in blood pressure in the afferent arteriole - Macula Densa cells detect a fall in NaCl in the distal tubule
- Stimulate granular cells to release renin - Sympathetic activation of granular cells
- Decrease blood pressure stimulates baroreceptor reflex
RAAS Process
- Granular cells secrete renin
- Renin activates angiotensinogen into angiotensin 1
- Angiotensinogen is a plasma protein (high concentration but inactive) - In lungs; angiotensin 1 converted into angiotensin 2 by angiotensin-converting enzyme (ACE)
- Angiotensin 2 triggers release of aldosterone (hormone) from adrenal cortex
- Aldosterone stimulates sodium reabsorption from distal tubule and collecting duct
*Sodium reabsorption “pulls” more water into the ECF (more salt and water in blood)
Tubular Secretion
- 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
Draw Renal Response to Haemorrhage
** See notebook for diagram
Micturition Reflex
- 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
Function of Urinary System
= Urine formation and carry urine
Innervation of Urinary System
- Parasympathetic (S2-4)
- Sympathetic (T12 - L2)
- Sympathetic (bladder neck)
- Somatic (S2-4) Pudendal nerve
Incontinence
- 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
Risk Factors of Incontinence
- Older age
- Female
- Pregnancy
- Childbirth
- Benign prostate hyperplasia and prostate cancer
- Type 2 diabetes
- Neurological disorders (e.g. stroke, PD)
- Dementia
- Possibly menopause
Stress Incontinence
- 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
Urge Incontinence
- Involuntary urination is proceeded by feelings of urgency
- Bladder muscle becomes overactive > involuntary contractions during filling
- Bladder oversensitivity from infection or neurological disorders
Overflow Incontinence
- Bladder does not completely empty and becomes distended
- Increased pressure overcomes sphincter control
- Urethral blockage
- Bladder unable to empty properly
Functional Incontinence
- Lack of recognition of need to urinate or inability to get to the toilet
- Causes: dementia, mobility issues, eyesight issues
Lifestyle and Behavioural Interventions as Treatment for Urinary Incontinence
- Weight loss
- Reduction of caffeine and alcohol intake
- Kegel exercise
- Bladder training
- Timed voiding
Pelvic Floor Exercises as Treatment for Urinary Incontinence
- Use right muscle and right technique
- Set exercise routine
- Maintain routine
Bladder Training as Treatment for Urinary Incontinence
- Behavioural intervention to re-establish bladder control in adults
- Program takes 3-6 months or more
Pharmacotherapy as Treatment for Urinary Incontinence
- 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
Surgery as Treatment for Urinary Incontinence
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
