What is the typical composition of urine?
Composition:
95% water
5% solutes and nitrogenous wastes
pH: 4.5-8 (slightly acidic)
Solutes:
- urea (majority)
- Na+ (sodium), PO43 (phosphates), SO42 (sulphates)
Nitrogenous wastes:
- urea (breakdown of amino acids)
- uric acid (breakdown of nucleic acids)
- creatainine (metabolite of creataine phosphate)
What are examples of an abnormal urine constitution?
Cloudy
Containing:
- blood proteins
- pus (WBCs)
- bile pigments
- glucose
- ketones
What are the 3 steps of urine formation?
- glomerular filtration
- in renal corpuscle
- water, salts, nutrient molecules and waste molecules move from the flomerulus to the inside of the glomerular capsule
- produces a filtrate - tubular reabsorption
- in renal tubule
- acgtive reabsorption of nutrient and salt molecules, and passive reabsorption of water molecules, into peritubular capillary network - tubular secretion
- in renal tubule
- addition of substances from blood in peritubular capillary network into filtrate
What is the filtration membrane?
Membrane in glomerular capsule that allows the movement of filtrate components from the glomerular capillaries into the glomerular capsular space
Membrane formed by:
- fenestrated endothelium of glomerular capillaries
- basement membrane
- podocytes of glomerular capsule (slits allow passage of molecules into capsular space)
Passing across membrane:
- molecules < 3mm
- water
- electrolytes
- glucose
- amino acids
- nitrogenous wastes
What is the glomerular filtration rate, and examples of normal and abnormal rates?
glomerular filtration rate (GFR) = volume of filtrate formed each minute by kidneys
Normal: > 90 mL/min
Abnormal: < 89 mL/min
Mild dysfunction: 60-89
Kidney failure: < 15 mL/min
At what glomerular filtration rate does kidney failure occur?
< 15 mL/min
Which 3 factors affect the glomerular filtration rate, and which one is altered by the body in order to adjust the GFR?
1.net filtration pressure (NFP)
(main controllable factor and main determinant of NFP)
- hydrostatic pressure of glomerular capillaries
- can be altered by altering blood volume or diameter of afferent arteriole (increased BV or increased blood flow to kidneys increases GFR)
- total surface area available
- filtration membrane permability
What are the 3 intrinsic and 2 extrinsic mechanisms for the regulation of GFR?
Intrinsic:
- Myogenic:
- vasoconstriction in response to high BP / high GFR
- vasodilation in response to low BP / low GFR - Tubuloglomerular mechanism (vasoconstriction):
- when GFR is too high, macula densa cells detect high NaCL (sodium) levels, and release adenosine to cause vasoconstriction of afferent arterioles and lower GFR - Prostaglandin E2 (vasodilation):
- produced by renal cells, maintain GFR by causing vasodilation of afferent arterioles when GFR is too low
Extrinsic:
- Hormonal (RAAS):
- when BP and GFR are low, juxtaglomerular cells release renin, which causes the RAAS cascade to increase BP, renal perfusion and GFR - Neural mechanism / baroreceptor reflex (RAAS):
- when BP is low, SNS acts on kidneys (B1 adrenergic receptors on juxtaglomerular cells); juxtaglomerular cells release renin to cause RAAS cascade, increase BP and GFR
Which intrinsic and extrinsic regulation mechanisms of GFR increase GFR, and which decrease GFR?
Increase or decrease:
- intrinsic myogenic mechanism (vasodilaltion to increase GFR, vasoconstriction to decrease GFR)
Increase:
- extrinsic hormonal mechanism (RAAS) to increase BP and GFR
- extrinsic neural / baroreceptor mechanism (RAAS) to increase BP and GFR
- intrinsic prostaglandin E2 mechanism: produced by renal cells, causes vasodilation of afferent arterioles
Decrease:
- intrinsic tubuloglomerular mechanism: macula densa cells release adenosine to cause vasoconstriction of afferent arterioles
Which 4 mechanisms can be activated in response to low GFR?
- Intrinsic myogenic mechanism - low GFR causes vasodilation of afferent arterioles
- Intrinsic prostaglandin E2 mechanism - low GFR causes release of PGE2 by renal cells to cause vasodilation of afferent arterioles
- Extrinsic hormonal (RAAS) mechanism - juxtaglomerular cells release renin, initiates RAAS cascade to increase BP, renal perfusion and GFR
- Extrinsic neural / baroreceptor (RAAS) mechanism - SNS activates B1 adrenergic receptors in juxtaglomerular cells to release renin, initiates RAAS cascade to increase BP, renal perfusion, and GFR
Describe the steps and actions of the RAAS mechanism
- Renin is released into the bloodstream by juxtaglomerular cells in the kidney, in response to extrinsic hormonal mechanism or extrinsic neural / SNS / baroreceptor mechanism
- Renin converts angiotensinogen (produced by liver) into angiotensin 1
- angiotoensin 1 is converted into angiotensin II by the angiotoensin-converting enzyme (ACE) produced by vascular endothelial cells in lungs
- Angiotensin II:
- causes vasoconstriction
- stimulates thirst reflex via hypothalamus
- stimulates release of aldosterone from adrenal glands
- stimulates release of ADH (anti-diuretic hormone) from posterior pituitary gland - Aldosterone:
- causes renal tubules to increase the reabsorption of sodium and water, increasing blood volume (and therefore BP) - ADH:
- causes increased water reabsorption at renal tubules, increasing blood volume (and therefore BP)
What are the 4 active hormones sand enzymes involved in the RAAS system, and what are their actions?
Renin:
- enzyme released by juxtaglomerular cells in kidney
- converts angiotensinogen into angiotensin
Angiotensin II
- conoverted from angiotensin I by ACE (angiotoensin converting enzyme)
- causes vasoconstriciton
- stimulates thirst reflex via hypothalamus
- stimulates release of ADH and aldosterone
ADH:
- hormone released by posterior pituitary gland
- increases water reabsorption at renal tubules
Aldosterone:
- corticosteroid hormone released by adrenal glands
- stimulates increased water and sodium reabsorption at renal tubules
What are the 4 main actions of the RAAS system to increase BP, and what triggers these actions?
Vasoconstriction:
- initiated by angiotensin II
Thirst reflex:
- via hypothalamus
- triggered by angiotensin II
Increased reabsorption of water at renal tubules:
- ADH
- released by posterior pituitary gland (in response to angiotensin II)
Increased reabsorption of water and sodium at renal tubules:
- aldosterone
- released by adrenal glands (in response to angiotensin II)
Which mechanisms can activate the RAAS?
Extrinsic neural mechanism:
- baroreceptors in the carotid sinus and aortic arch detect low BP
- SNS activation via CNIX glossopharyngeal and CNX vagus stimulate juxtomedullary cells in kidneys to release the enzyme renin (triggering RAAS cascade to increase blood volume, renal perfusion, and blood pressure)
What are the direct renal mechanisms in response to high or low blood volume / GFR rates in the kidneys/
High blood volume / blood pressure = high GFR:
- if too high, kidneys can’t reabsorb filtrate rapidly enough
- more filtrate leaves the body as urine, causing BV / BP to drop
Low blood volume / blood pressure / GFR:
- water conserved by kidneys and returned to bloodstream
- causes BV / BP / GFR to increase
Which substances are reabsorbed at the 3 different components of the renal tubules and duct?
- Proximal collecting tubule
- water (passive)
- chloride, potassium, calcium (passive)
- urea (passive)
- sodium, bicarbonate (active)
- glucose, amino acids, vitamins (active) - Descending loop of Henle
- water (passive) - Ascending loop of Henle
- calcium (passive)
- sodium, chloride, potassium (active) - Distal convoluted tubule and collecting duct
- water and electrolytes (hormone mediated)
In which parts of the renal tubule and collecting duct is water reabsorbed into the bloodstream?
- proximal convoluted tubule (passive)
- descending loop of henle (passive)
- distal convoluted tubule and collecting duct (hormone-mediated)
Which 4 hormones mediate the reabsorption of water and electrolytes at the distal convoluted tubule and collecting duct?
- ADH (anti-diuretic hormone)
- released by posterior pituitary gland
- increases reabsorption of water - by increasing permeability of DCT and CD to water (inserts aquaporins into apical membrane of tubule cells) - Aldosterone
- released by adrenal gland as part of RAAS cascade in response to low BV / BP
- enhances reabsorption of sodium at DCT and CD - Atrial Natriuretic Peptide (ANP)
- released by cardial atrial cells when BP / BV is elevated
- inhibits reabsorption of sodium at DCT and CD - Parathyroid hormone
- increases passive reabsorption of calcium at DCT
What are the actions of ADH, and when is it released into the bloodstream?
ADH = anti-diuretic hormone
- released by posterior pituitary gland in response to dehydration (low BV / BP) or increased ECF osmolarity
- increases reabsorption of water at distal convoluted tubule and collecting duct
What are the actions of atrial natriuretric peptide (ANP)?
- produced by cardiac atrial cells when BP / BV is too high
- inhibits reabsorption of sodium at distal convoluted tubule and collecting duct
What are the actions of parathyroid hormone on the kidneys?
- increases reabsorption of calcium at the distal convoluted tubule
Describe the difference between active and passive reabsorption in the renal tubules and collecting ducts.
Passive:
- osmosis, diffusion and facilitated diffusion across the membrane of the tubule into the bloodstream
Active:
- primary and secondary active transport
What are the 4 types of substances that are secreted from the bloodstream back into filtrate in the renal tubules and collecting duct?
- some drugs
- metabolites reabsorbed passively:
- urea and uric acid - Excess potassium (K+)
- driven by aldosterone at the DCT and CD (aldosterone increases reabsorption of sodium Na+, which must be balanced by potassium) - acids and bases
- dependent on blood pH
- hydrogen, hydrochloride, ammonium
In which areas of the renal tubules and collecting duct are substances secreted back into the filtrate?
Distal convoluted tubule:
- ions
- acids
- drugs
- toxins
Collecting Duct:
- sodium (Na+)
- potassium (K+)
- hydrogen
- bicarbonate ions
