renal system physiology Flashcards
What are the 2 key non-renal functions of the kidney?
Hormone release, Metabolic functions
What are the hormones released by the kidneys?
Erythropoietin, calcitriol (activated Vitamin D)
What is the role of the kidneys in acid-base balance?
Synthesis HCO3 to maintain pH, excrete non-volatile acids
What is the relationship between arterial blood pressure and glomerular hydrostatic pressue and GFR?
As blood pressure drops, glomerular hydrostatic pressure drops and so too does GFR
What are the intrinsic/autoregulation mechanisms thats regulate renal blood flow and GFR?
- Tubulo-glomerular feedback - sodium levels in the macula densa feedback to vasoconstrict the afferent or efferent arteriole to alter GFR
- Myogenic mechanism - afferent arteriole responds to stretch/pressure and contracts in response to high pressure/dilates in response to low pressure
What process occurs when the macula densa senses low sodium?
Activates renin, which triggers conversion of Ang I to Ang II, and results in constriction of the efferent arteriole to raise GFR
What process occurs when the macula densa senses high sodium?
Reduces renin releases, therefore vasodilating the efferent arteriole to reduce GFR
How do high levels of Ang II affect glomerular blood flow?
While low levels of Ang II cause efferent arteriole constriction for intrinsic auto-regulation of GFR, high levels will activate afferent arteriole vasoconstriction, which provides an extrinsic reduction in renal blood flow.
What are the extrinsic mechanisms that regulate renal blood flow?
- Angiotensin II - acts on afferent arterioles when in high doses to reduced glomerular blood flow to preserve blood volume.
- Sympathetic innervation - nerve activation acts to restrict afferent arterioles to reduce GFR
- Prostaglandins - Vasodilate afferent arterioles to increase renal blood flow.
What is the Glomerular Filtration Rate?
The rate at which blood is filtered at the glomerulus
What factors determine the effective filtration pressure?
Hydrostatic and osmotic pressures in the glomerular capillaries, and the Bowman’s capsule
What is hydrostatic pressure?
Pressure exerted by fluid (blood/filtrate)
What is colloid osmotic pressure?
Pressure exerted by proteins - drives fluid towards the protein
How is GFR calculated for a solute that is completely filtered by the kidneys with no secretion/reabsorption?
GFR = (Urine volume * Urine Concentration)/Plasma Concentration
GFR = (UV/P)
Which substances are completely filtered by the kidneys with no reabsorption or secretion?
Creatinine, inulin
Which clearance value can be used to determine GFR?
Creatinine clearance
Which parts of the nephron are involved in reabsorption?
Proximal tubule, Descending loop of Henle, Ascending loop of Henle, Distal tubule, Collecting Duct
Which solutes are only reabsorbed, but not secreted by the renal tubule?
Glucose, water, sodium, chloride, phosphate, calcium
Which solutes are only secreted, and not reabsorbed by the renal tubule?
organic cations/anions (includes drugs, monoamines, neurotransmitters, etc.)
Which solutes are secreted and reabsorbed by the renal tubule?
Potassium, ammonia, hydrogen ions, bicarbonate, urea
What is the main function of the proximal convoluted tubule?
Bulk reabsorption of water and many solutes, including bicarbonate, sodium, chloride, phosphate, potassium, amino acids and glucose.
(there is also some secretion of organic acids, H+ and drugs)
What structural features of the proximal tubule epithelium allow for its reabsorptive function?
Microvilli increase surface area, abundant mitochondria provide energy for sodium pumps for co-transport of sodium and glucose
How and where is glucose reabsorbed in the nephron?
Reabsorbed with sodium at co-transporters in the proximal tubule
How and where are amino acids reabsorbed in the nephron?
Reabsorbed with sodium at co-transporters in the proximal tubule
What are the 2 key functions of the Loop of Henle?
- Establishes concentration gradient for water reabsorption in the Collecting Duct
- Urine sodium dilution/concentration
What are the 3 functional parts of the Loop of Henle?
Descending limb, Thin ascending limb, thick ascending limb
How is the Hyper Osmotic Medullary Gradient generated, via the countercurrent multiplication system?
- Filtrate enters the descending loop, which is permeable to water but not sodium. Water moves down gradient into the interstitium which is hyperosmotic, increasing sodium concentration in the loop.
- Filtrate enters the thin ascending loop, which is permeable to sodium but not water. Sodium passes into the medulla interstitum.
- NKCC2 co-tranporters pump sodium into the interstitium, creating a gradient that drives water reabsorption, particularly in the collecting duct
How is the Hyper Osmotic Medullary Gradient generated, via the countercurrent vasa recta system?
- Blood enters the vasa recta, as it descends into the medullar it absorbs sodium from the hyperosmotic interstitium
- As blood ascends the medulla it secretes sodium that will be absorbed by the descending parts of the vasa recta that sit near by - keeping the sodium in the medulla
What is the structural significance of the epithelium of the thin limbs of the Loop of Henle?
Simple squamous epithelium - thin layer so that there is a short distance for solutes to travel between the limb and the vasa recta/medullary interstitium to generate the HOMG
What is the structural significance of the epithelium of the thick ascending limb of the Loop of Henle?
Simple cuboidal epithelium with basolateral indigitations, improves active sodium transport via NKCC2 co-transporters
What is the nature of the filtrate when it leaves the loop of Henle?
Filtrate is fairly dilute - electrolytes will be added back in in the distal tubule
What is the function of the distal tubule?
Electrolyte fine tuning - sodium and water reabsorption, K and H+ secretion. Sodium levels influence macula densa for RAAS activation
What is the main difference between the epithelium of the proximal and distal tubules?
Both are simple cuboidal - but proximal has microvilli for glucose and amino acid reabsorption, and distal does not
What are the electrolyte/acid-basebalancing processes that occur in the distal tubule?
- Sodium and chloride are actively reabsorbed by a co-transporter
- Potassium is secreted.
- pH maintained by secreting H+ ions and reabsorbing bicarbonate ions to alkalise the blood if necessary
What are the electrolyte/acid-basebalancing processes that occur in the distal tubule?
- Sodium and chloride are actively reabsorbed by a co-transporter
- Potassium is secreted.
- pH maintained by secreting H+ ions and reabsorbing bicarbonate ions to alkalise the blood if necessary
Which hormone influences electrolyte balance in the distal tubule, and how?
Aldosterone - increases sodium reabsorption and increases potassium secretion
What is the main function of the collecting duct?
Water reabsorption
What are the 2 factors that drive water reabsorption in the Collecting Duct?
- Hyper-Osmotic Medullary Gradient drives water from inside collecting ducts to the osmotic medulla
- ADH alters permeability of CD by inserting aquaporins that facilitate water reabsorption
What type of epithelium is found in the collecting ducts?
Simple columnar
What are the 2 key cell types of the Collecting Duct, and what are their functions?
Intercalated cells - H+/K+ exchange (for acid-base and potassium balance)
Principal cells - Site of Anti Diuretic Hormone activity (aquaporin insertion). Na/K exchange stimulated by aldosterone
What is the body water percentage for males?
60%
What is the body water percentage for females?
55%
What are the two compartments of body water, and their proportions?
Intracellular fluid (2/3), Extracellular Fluid (1/3)
What are the predominant solutes in the extracellular fluid?
Sodium, chloride
What are the predominant solutes in the intracellular fluid?
Potassium (+ organic anions)
What are the two components of the ECF, and what are their relative proportions?
20% plasma, 80% interstitial fluid
What feature of body water allows for free movement of water from the ECF to ICF via a semipermeable membrane?
The osmolarity of the ECF and ICF are normally the same - this allows for fluid to move if the osmolarity of one compartment changes to equalise
What is the effect on osmolarity if water is lost from a compartment?
Osmolarity increases - concentration of solutes becomes higher
What mechanisms detect and correct changes in plasma/ECF osmolarity?
- osmoreceptors in the hypothalamus detect a rise in plasma osmolarity
- signals to posterior pituitary to secrete ADH
- ADH increases permeability of the collecting duct via aquaporins to drive water reabsorption and restore plasma osmolarity
What are the 2 major stimuli for the release of ADH?
- Increased ECF osmolarity
- Decreased blood volume/drop in blood pressure
What are the 2 main sources of acid in the body?
Carbon Dioxide produced by cells, Non-volatile acids produced by metabolism
What are the 2 ways that the kidneys handle bicarbonate?
- ‘reabsorption’ of filtered bicarb by synthesising HCO3 in the PT to replace filtered ions
- replacement of HCO3 consumed by buffering by synthesising it in the tubules
What is the process of bicarbonate ‘reabsorption’ in the kidneys?
- Bicarb is filtered and enters the lumen of the proximal tubule
- Bicarb binds with hydrogen ions secreted by the tubular cells into the lumen forming H2O and CO2.
- H2O and CO2 move into the tubular cells and are converted to bicarb’
- Bicarb is reabsorbed into the blood stream to replace filtered ions
What is the process of the replacement of bicarbonate consumed in buffering the kidneys?
During the excretion of non-volatile acids, HCO3- and H+ will be formed from CO2 and H2O. The H+ will bind to the acid and be excreted, while the remaining bicarb can be absorbed into the bloodstream.
What triggers the production of aldosterone?
Ang II from RAAS activation
Where is aldosterone formed?
The zona glomerulus of the cortex of the adrenal gland.
What part of the nephron does aldosterone act on?
The distal tubule and collecting duct
What are the functions of Angiotensin II (Ang II)?
- potent vasoconstrictor to increase blood pressure
- Triggers aldosterone release
- Tiggers ADH release
- Increases GFR by constricting efferent arteriole
- At HIGH doses due to severe haemorrhage or hypotension, will constrict afferent arteriole to reduce renal blood flow and preserve blood pressure/volume
What are the the 3 triggers for renin release?
- Decreased flow through the afferent arteriole
- Decreased blood pressure in the carotid bodies/aortic arch and sympathetic nerve activation
- Decreased sodium delivery to the distal tubule, sensed by the macula densa
What is the process of formation of Ang II?
Renin causes release of Ang I, which is converted to Ang II by ACE (Angiotensin Converting Enzyme)
