Renal System Flashcards
Describe the structure of the nephron
List the 6 main function of the kidneys
Regulation of ECF volume and BP
Regulation of osmolarity
Maintenance of ion balance
Homeostatic regulation of pH
Excretion of wastes
Production of hormones
Give an overview of nephron function
Renal corpuscle (glomerulus + Bowman’s capsule) = filtration of mostly protein-free plasma from the capillaries into the capsule
Proximal tubule = isoosmotic reabsorption of organic nutrients, ions, and water. Secretion of metabolises and xenobiotic molecules such as penicillin
Loop of Henle = reabsorption of ions in excess of water to create dilute fluid in the lumen. COuntercurrent arrangement contributes to concentrated interstitial fluid in the renal medulls
Distal nephron (distal tubule + collecting duct) = regulated reabsorption of ions and water for salt and water balance and pH homeostasis
What is Glomerular filtration pressure, what is it comprised of and how is it calculated?
The net filtration pressure between the glomerulus and nephron lumen
Comprised of:
Hydrostatic pressure (BP)
Colloid osmotic pressure (oncotic pressure) - osmotic pressure of water trying to stabilise molecular concentration (i.e. proteins)
Fluid pressure generated by fluid in Bowmans capsule (balloon expansion)
Describe glomerular filtration rate?
Only 20% of the plasma that passes through the glomerulus is filtered
Less than 1% of filtered fluid is excreted
Rate is relatively constant (despite BP changes)
What filtration barriers exist between the glomerulus and lumen of Bowmans capsule?
Podocyte = cell with feet.
Mesangial cell = supporting cell
- Contains actin and can change its shape, pulling capillaries, opening and closing gaps, altering blood flow
Blood filtered through glomerular capillary endothelium, basal lamina and Bowmans capsule epithelium
What factors impact glomerular filtration rate?
Influenced by two factors:
Net filtration pressure = Hydrostatic pressure - colloid osmotic pressure - fluid pressure
Filtration coefficient = SA of glomerular capillaries available for filtration; Permeability of interface between the capillary and Bowman’s capsule
What factors autoregulate glomerular filtration rate?
- Myogenic response
Intrinsic ability of vascular smooth muscle to respond to pressure changes (stretch receptors)
As BP goes up, diameter goes up. Myogenic response then contracts these arterioles
Similar to autoregulation in other systemic arterioles
- Tubuloglomerular feedback
Paracrine control
Macula densa cells sense distal tubule flow and release paracrines that impact afferent arteriole diameter. Can release ATP, nitric oxide, adenosine
Macula densa also detects Na concentration- signals granular cells which secrete the enzyme renin
- Hormones and autonomic neurons
By changing resistance in arterioles
By altering filtration coefficient
Describe the juxtaglomerular apparatus
Describe tubuloglomerular feedback
What are the tranepithelial and paracellular pathways for reabsorption in the proximal tubule?
Lumen surrounded by epithelial cells which have transporters
Active pumping of Na+ generates an electrochemical gradient which drives anion reabsorption. This then drags water across via osmosis which increases concentration of other solutes, causing them to diffuse
What are the transporters in the proximal tubule which reabsorb Na+?
Sodium hydrogen exchanger (NHE)
Epithelium sodium channel (ENaC)- selectively actively transports sodium
Sodium-glucose linked symporter (SGLT)
Sodium-potassium pump
Can renal transporters reach saturation and what form does this take?
Yes, all renal transporters share this characteristic. Their workload is proportional to plasma concentration until their transport maximum (Tm) is reached
Since filtration is proportional to the plasma concentration and doesnt have a maximum threshold:
Excretion = Filtration - Reabsorbtion
Why does peritubular capillary pressure favour reabsorption?
Pressure drops becuase capillaries start branching
Pressure favours filtration in glomerulus but reabsorption in peritubular capillaries
What is secretion and why is it important?
Secretion is the transfer of molecules from ECF back into the lumen of the nephron. It is an active process (primarily indirect) important in homeostatic regulation of K+ and H+. Increasing secretion enhances nephron excretion. It is a competitive process
What is the mechanism for organic anion secretion?
- Na/K ATPase pumps Na+ out of ICF
- NaDC symporter transports aKG (alpha keto glutarate) with Na into the ICF using energy stored in the Na concentration gradient
- OAT antiporter transports organic ions into the ICF and aKG out of the ICF using energy stored in the aKG concentration gradient
- Organic anions enter the lumen via facilitated diffusion (some debate over exact mechanism)
What is excretion and how does it relate to renal clearance?
Excretion = filtration - reabsorption + secretion
Clearance:
- Rate at which a solute disappears from the body by excretion or by metabolism
- Non-invasive way to measure GFR (easy work out filtration rate, since we known the concentration in the blood and the amount secreted)
- Inulin (not insulin) and creatinine are used to measure GFR (these molecules are not reabsorbed or secreted)
Describe the integrative response to a change in blood volume
Homeostasis of water and electrolytes depends on the integration of kidneys, respiratory and cardiovascular systems
Thirst and craving for salt are behavioural mechanisms
Intake and loss of water are balanced
How does osmolarity vary between the Loop of Henle, distal tubule and collecting duct?
- In descending loop of Henle, primarily only water is reabsorbed (increases osmolarity)
- In ascending loop of Henle, primarily only ions are reabsorbed via active transport (decreases osmolarity)
- In distal tubule, reabsorption is variable and is regulated by hormones
- Final urine osmolarity depends on reabsorption in collecting duct (also variable and regulated by hormones)
What role does vasopressin play in water reabsorption in the nephron?
Vasopressin is a hormone released from the posterior pituitary. It triggers increased water reabsorption in the nephron to conserve water.
It does this by inserting water pores into apical membranes of the collecting duct, making them permeable to water. Water leaves by osmosis and is carried away by the vasa recta capillaries. Urine is concentrated. Linked to the countercurrent exchange mechanism
Describe the renal countercurrent exhange mechanism
- The renal countercurrent exchange system consists of closely associated tubules and capillaries of the vasa recta
- Countercurrent multiplier transfers solutes by active transport into the medulla
- Vasa recta removes water and prevents dilution of the medulla interstitial fluid
On the way up, blood is meeting filtrate at lower osmolarity. This causes water to enter the blood, decreasing its osmolarity, and increasing the osmolarity of the filtrate
At the same time blood going down at low osmolarity is in close proximity with blood going up at high osmolarity. This causes osmosis again, increasing osmolarity at the bottom of the loop and decreasing it at the top
Describe the pathway by which vaspressin is released and used
Describe the collecting duct in the prensence of vaspressin
Describe the collecting duct in the absence of vaspressin
What is the general response to salt ingestion?
What is the primary action of aldosterone
Aldosterone is a steroid hormone released from the adrenal cortex in response to Angiotensin II from the renin-angiotensin system.
It responds to low salt in kidney/ decreased BP, increased K+ concentration by increasing Na reabsorption and K secretion
Describe the mechanisms of aldosterone
Describe the Renin-Angiotensin System (RAS) in depth
What are natriuretic peptides?
Biomarkers for heart failure
Sodium loss = natriuresis
Water loss = diuresis
Natriuretic peptides work to excrete salt
Opposite of renin-angiotensin system
Describe the homeostatic compensation to severe dehydration
*CVCC = cardiovascular control centres;
*normally ANG II causes adrenal cortex to release aldosterone, but not in this case. Osmolarity inhibits this release. Integration
What is normal plasma pH and how does pH imbalance impact the body?
Normal pH of plasma is 7.38-7.42
H+ concentration is closely regulated
- Changes can alter three-dimensional structure of proteins
Abnormal pH impacts the nervous system
- Acidosis = neurons become less excitable; CNS depression
- Alkalosis = hyperexcitable
pH disturbances
- Associated with K+ disturbances (H+/K+ exchange)
What are the inputs and outputs of H+ in the body?
CO2 + H2O <–> H2CO3 <–> H+ + HCO3-
What 3 ways is pH regulated in the renal system?
Receptor-mediated endocytosis
Directly by excreting or reabsorbing H+
Indirectly by changing in the rate at which HCO3- buffer is reabsorbed or excreted
What role does the proximal tubule play in pH regulation?
It reabsorbs filtered bicarbonate and secretes H+
What role does the distal tubule play in pH regulation?
Controls the majority of acid secretion
*CA = carbonic anhydrase
List the transporters involved in kidney pH regulation
