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Responding to ill Health
Life Science
The Urinary System
Madhero88 (2009)
https://commons.wikimedia.org/wiki/File:FullUSys_copy.png
1
Learning Outcomes
•
Identify the body fluid compartments, and describe the gross and
microscopic structure of the kidney
•
Outline the multiple roles of the urinary system in maintaining homeostasis
•
Explain urine production related to nephron structure and the processes of
filtration, selective reabsorption and tubular secretion.
•
Explain the hormonal regulation of urine composition and volume, and the
homeostatic role of the kidney in producing renin and erythropoeitin
2
Functions of Kidney
• Excretion of nitrogenous waste (breakdown of
proteins)
• Regulation of blood pH (acidity/alkalinity)
• Regulation of electrolyte balance (salts)
• Regulation of blood volume and blood pressure
• Production of hormones
– Calcitriol – vit. D – maintains calcium levels
– Erythropoietin – red blood cell production
– Homeostasis!
3
Relevance
• Renal Disease indicates range of renal function
e.g.
•
•
•
•
•
•
•
fluid problems e.g. oedema
waste accumulation e.g. uraemia
electrolyte imbalance e.g. hyperkalaemia
acid/base imbalance e.g. acidosis
hypertension e.g. blood volume, renin
anaemia e.g. lack of erythropoietin
musculoskeletal e.g. gout
4
Kidney Function – Elimination of waste
– Nitrogen from protein breakdown
•
Amino acids contain Nitrogen atom which is
removed (Deamination) in liver, creating
Ammonia (NH3) - highly toxic
•
The liver further converts Ammonia to Urea
•
Urea is much less toxic than Ammonia, but
must still be excreted
•
Liver Disease
– can’t convert the toxic ammonia to urea
– encephalopathy
•
Kidney Disease – urea can be made but kidneys can’t excrete - uraemia
•
Both conditions may be fatal
5
Other nitrogenous waste
• Breakdown of Nucleic acids e.g. DNA forms
waste product URIC ACID
Hellerhoff (201)
https://commons.wikimedia.org/wiki/File:Gichtfuss_im_Roentgenbild_002.png
• Excess uric acid in blood causes gout
• Crystals of uric acid in joints – very painful!
Arnaudus (2004)
https://commons.wikimedia.org/wiki/File:AcideUrique.png
6
Bobjgalindo (2005)
https://commons.wikimedia.org/wiki/File:Fluorescent_uric_acid.JPG
2. Tubular selective
reabsorption
Madhero88 (2010) Physiology of Nephron
https://commons.wikimedia.org/wiki/File:Physiology_of_Nephron.png
Urine formation – 3 key processes
1. Glomerular
filtration
7
Madhero88 (2010) Physiology of Nephron
https://commons.wikimedia.org/wiki/File:Physiology_of_Nephron.png
Urine formation
1. Glomerular
filtration
8
Glomerulus
Blood :
• arrives at glomerulus via
afferent arteriole
• exits glomerulus via
efferent arteriole
• Each kidney receives 1200ml
blood/min
• 25% of cardiac output
• Renal blood flow kept at constant
pressure (independent of systolic
pressure)
• Controlled by juxtaglomerular
apparatus (part of DCT)
OpenStax College (2013)
https://commons.wikimedia.org/wiki/File:Juxtaglomerular_Apparatus_and_Glomerulus.jpg?uselang=en-gb
Glomerular Filtration
• Pressure in
glomerular
capillaries is
55mmHg
• Body capillaries
usually 25mmHg
• Glomerular
capillaries covered
in special
connective tissue –
Capsular
epithelium –
prevents bursting
NET filtration pressure
=55-(15+30) = 10 mmHg
3. Blood colloid osmotic
pressure = 30 mmHg
2. Capsular hydrostatic
pressure = 15 mmHg
1. Glomerular capillary pressure
= 55 mmHg
10
Henry Gray (1918) Gray1130
https://commons.wikimedia.org/wiki/File:Gray1130.svg + UWS Staff (2015)
Filter Layers of wall of capillaries
• Podocyte cells of capsular epithelium – interlocking mesh
• Cells and plasma proteins too big to filter - stay in blood
• Damage to capsular epithelium – wider holes - protein passes through Proteinuria
OpenStax College (2013)
https://commons.wikimedia.org/wiki/File:2613_Podocytes.jpg?uselang=en-gb
11
Glomerular filtration
Na+
glucose
proteins
BOWMAN’S
CAPSULE
filtrate
ClH 2O
H 2O
Na+
Cl-
N.B Concentration
of Glucose and
Sodium Chloride is
the same in filtrate
as plasma but not
plasma proteins.
glucose
•Glomerular damage – Nephrotic syndrome
• Proteinuria (protein in urine)
• Plasma protein ↓
• Fluid movement: blood → tissue - Oedema
• e.g. Pre-eclampsia – hypertension during pregnancy
James Heilman, MD (2010)
https://commons.wikimedia.org/wiki/File:Combinpedal.jpg
UWS Staff (2015)
GLOMERULUS Blood cells
blood
Plasma
Glomerular filtration rate (GFR)
• Each kidney receives 1200ml blood/min
• Glomerular filtration rate – amount of filtrate formed per
minute ~120ml/min
• But ~119ml/min reabsorbed leaving 1ml/min of urine =
60ml/hour = 1440ml/day
• GFR can be measured to assess kidney function
• Patient drinking normally – 60ml urine/hour
• Less than 30ml/hour = kidneys not functioning properly
13
Glomerular Filtration
• If GFR = 120ml/min then would mean
180 litres formed per day (but we
only have 5L of blood!)
• Must reabsorb the majority or we’d
die from hypovolaemic shock in
minutes
• Reabsorption occurs in tubules of
nephron
• Filtrate returned to blood in
peritubular capillaries
Burton Radons (2012)
https://commons.wikimedia.org/wiki/File:Nephron_illustration.svg?uselang=en-gb
2. Tubular selective
reabsorption
Madhero88 (2010) Physiology of Nephron
https://commons.wikimedia.org/wiki/File:Physiology_of_Nephron.png
Urine formation
15
Reabsorption
• Active or passive
• Passive - depends on concentration/or pressure
gradients
• Osmosis (water movement) important
– Plasma osmotic pressure is higher than the filtrate – due
to plasma proteins
• Active transport systems use energy
Selective tubular reabsorption
• Reabsorption of important filtrate components
into blood (via peritubular capillaries)
• Mainly in proximal convoluted tubule (PCT)
• As plasma moves along peritubular capillaries
[glucose] and [sodium] gets higher
– (so [water] is lower)
• Water follows by osmosis from PCT to peritubular
capillaries
17
Selective Reabsorption
•
•
•
•
Sodium is filtered yet most of it reabsorbed
Requires energy
So why filter it??
Homeostasis requires precise control of
sodium levels
• In deficiency, reabsorb more
• If in excess, reabsorb less
Selective Reabsorbtion
Glucose & amino acids
• normally completely reabsorbed (none in urine)
Sodium & chloride
• reabsorbed - both active & passive transport
Diabetes mellitus
• Excess blood glucose
• Too much glucose filtered - can’t all be
reabsorbed – Glycosuria
• Less water is reabsorbed as a result – dilute urine
Reabsorption
• Substances not reabsorbed in the
PCT now move into the Loop of
Henle
• Further 20% water and salt are
reabsorbed here
• High [Solute] concentration in
medulla - helps osmosis from
collecting ducts (to concentrate
urine)
OpenStax (2013)
https://commons.wikimedia.org/wiki/File:2621_Loop_of_Henle_Countercurrent_Multiplier_System.jpg?uselang=en-gb
Urine formation
3. Tubular secretion
• Active process
Madhero88 (2010) Physiology of Nephron
https://commons.wikimedia.org/wiki/File:Physiology_of_Nephron.png
• Opposite direction to
reabsorption
• Substances not required by
body secreted in urine
• Drug secretion (e.g. penicillin,
aspirin)
• Hydrogen ion secretion,
removes excess acid from
body (controls blood pH)
21
Tubular Secretion
• Blood pH range 7.35 - 7.5
• Blood pH ↓ - then H+ ions secreted from plasma
• Bicarbonate (buffer) ions reabsorbed into plasma
• Urine pH indicates health of DCT
• If plasma pH low, urine pH even lower (H+ secretion)
Kidney disease
• Plasma pH falls below 7.35 - acidosis
• Patient may be acidotic but urine pH normal as DCT not
secreting
Summary - TUBULAR PROCESSES
Glomerular filtration :
(plasma minus plasma proteins
PCT :
Fixed reabsoption
Glucose
Amino Acids
65% of
Sodium
Chloride
Water
DCT :
Controlled reabsorption of
sodium by ALDOSTERONE
LOOP OF HENLE :
Fixed reabsorption
20%
Sodium
Chloride
Water
NOTE THAT FIXED REABSORPTION HAPPENS AUTOMATICALLY !
CONTROLLED REABSORPTION OCCURS THROUGH HORMONAL EFFECTS !
Burton Radons (2012)
https://commons.wikimedia.org/wiki/File:Nephron_illustration.svg?uselang=en-gb
COLLECTING DUCT :
Controlled reabsorption of
water by –
ADH
Hormonal control of reabsorption
• Fluid passes from loop of
Henle into the Distal
Convoluted Tubule (DCT)
• DCT is site of final
reabsorption of Na+
• Regulated by Aldosterone
secreted by adrenal glands
Burton Radons (2012)
https://commons.wikimedia.org/wiki/File:Nephron_illustration.svg?uselang=en-gb
Hormonal control
Aldosterone 
– increased reabsorption of sodium and
water
– increased potassium secretion into
urine
– Ion exchange
– Result: ↑ Blood pressure (BP)
– Aldosterone production regulated by
kidneys
– Low BP, Na+ or blood volume → kidney
secretes enzyme RENIN (enzyme)
– Initiates Renin-Angiotensin System
(RAS)
25
EEOC (2006)
https://commons.wikimedia.org/wiki/File:Illu_adrenal_gland.jpg
Renin Angiotensin System
Angiotensin II
powerful vasoconstrictor (↑ BP)
 also stimulates adrenal cortex
to produce aldosterone
 Aldosterone ↑ Na+ reabsorption
in DCT
26
UWS Staff (2015)
Final stage of urine formation
• Collecting duct (CD)
receives the filtrate from
DCT
• CD moves through the renal
medulla toward renal pelvis
• Final reabsorption of water
occurs
• Under hormonal control
from Antidiuretic Hormone
(ADH)
Burton Radons (2012)
https://commons.wikimedia.org/wiki/File:Nephron_illustration.svg?uselang=en-gb
ADH concentrates urine
• High blood osmotic pressure  ADH
secretion
• ↑ permeability of walls of DCT & collecting
ducts (channels opened)
• ↑ osmosis & water reabsorption
• Urine becomes more concentrated
Diabetes insipidus
• Insufficient ADH
• Collecting ducts less porous
• Large volume of dilute urine produced
28
ADH
• If you drink too much (overhydrate)
• levels of ADH drop
• less water is reabsorbed from CD
• large volume DILUTE urine produced
• If drink too little (dehydrated)
• high ADH levels
• maximal reabsorption water from CD
• CONCENTRATED urine
The Kidneys and Hypertension
• Hypertension can be due to
– Excess ADH causing increased blood volume
– Excess Aldosterone causing Na+ retention
• Hypertension is both an effect of renal disease
and a cause of renal disease
• Patients with kidney disease
– Malignant Hypertension (Hypertensive Emergency)
– CNS, CVS, kidneys impaired
– May be irreversible damage
• Stimulates production of red blood cells
from bone marrow
• Low oxygen levels → kidneys release EPO
(altitude training)
• ‘Doping’ in sport
Calcitriol
• Hormonal form of vitamin D
• Aids calcium absorption in GIT
• ↑ tubular reabsorption of calcium from glomerular filtrate
(prevents excretion)
de:Benutzer:Hase (2002)
https://commons.wikimedia.org/wiki/File:Lance_Armstrong_MidiLibre_2002.jpg
Erythropoietin (EPO)
Erik van Leeuwen (2013)
https://commons.wikimedia.org/wiki/File:Mo_Farah_(2)_Moscow_2013.jpg?uselang=en-gb)
Hormones released by kidney:
31
WATER AND ELECTROLYTE BALANCE
Electrolytes
• salts & ions dissolved in water
• Osmotic pressure of body fluids
• Essential roles in physiology
UWS Staff (2015)
Biezl (2008)
https://commons.wikimedia.org/wiki/File:Gibbs-donnan-en.svg
Water Balance
• Need to avoid dehydration/overhydration
– Usual intake 2500ml/day
• Causes of dehydration :
–
–
–
–
–
Poor intake
Sweating
Diarrhoea
Diuretics
Diabetes
Water Gain
Water Loss
Metabolism (200 ml)
Food (700 ml)
Drinking (1600 ml)
Faeces (100 ml)
Exhaled (300 ml)
Evaporation from skin (600
ml)
Urine (1500 ml)
• Overhydration can be caused by
UWS Staff (2015)
– Excessive intake
– Insufficient excretion from kidneys (kidney failure or excess ADH)
• Acute renal failure patients usually need
restricted fluid intake
Electrolyte Balance
Sodium
• Na+ is major (+) ion in extracellular fluid (ECF) and essential for nerve
and muscle function
• Excess salt removed by kidneys (↓ aldosterone)
• XS sodium retention → water retention to maintain osmotic pressures
→ increases ECF and plasma volume → increased blood pressure
Potassium
• K+ major intracellular ion (ICF) (ECF levels are low)
• Essential for normal nerve and muscle function
• Changes in K+ harmful to the heart (lethal injection – potassium
chloride)
Electrolyte Balance - calcium
•
•
•
•
Ca2+ abundant in dairy and fish
Absorption in GIT is inefficient - Vit D aids this
Most stored in bone but some in ECF and ICF
Parathyroid hormone major controller
• Ca2+ roles:
–
–
–
–
Muscle contraction
Blood clotting
Activation of complement immunity
Nerve and muscle (including cardiac) function
Hypocalcaemia
• ↑ excitability of nerve /muscle → muscle spasms
Hypercalcaemia
• muscle weakness
• Kidney stones
• Bone softening