Renal Physiology 1 Flashcards
1
Q
What are the functions of the kidneys?
A
- Regulation of ECF volume and blood pressure.
- Regulation of osmolarity.
- Maintenance of ion balance.
- Regulation of pH → HCO3- and H+.
- Excretion of waste.
- Production of hormones.
2
Q
Approximately how many nephrons are found in each kidney?
A
- ~1000,000
- This number naturally declines with age or in disease.
3
Q
Describe the structure of a nephron.
A
- Each nephron contains:
- A tuft of glomerular capillaries (glomerulus), through which large volumes of fluid are filtered from the blood.
- A long tubule in which the filtered fluid is converted into urine on its way to the renal pelvis.
4
Q
Describe the structure of the glomerulus.
A
- Glomerulus contains a network of branching and anastomosing glomerular capillaries that have a high hydrostatic pressure (~60mmHg).
- Glomerulus is covered by epithelial cells → total glomerulus is encased in the Bowman’s capsule.
5
Q
Describe the system of tubules in the nephron.
A
- Fluid → filtered from the glomerular capillaries into the Bowman’s capsule → then into the proximal tubule → loop of Henle, which dips into the renal medulla.
- Thin segment of the loop → the walls of the descending limb and the lower end of the ascending limb are very thin.
- At the end of the thick ascending limb → a short segment that has a segment of specialised epithelial cells = macula densa.
- The fluid then enters the distal tubule, which similarly to the proximal tubule, lies in the renal cortex.
- The distal tubule is followed by the connecting tubule and the cortical collecting tubule, which leads to the cortical collecting duct.
- The initial parts of 8-10 cortical collecting ducts join to form a single larger collecting duct that runs downward into the mediulla and becomes te medullary collecting duct.
- The collecting ducts merge to form progressively larger ducts, that eventually empty into the renal pelvis through the tips of the renal papillae.
- In each kidney there are ~250 of the very large collecting ducts, each of which collects urine from ~4000 nephrons.
6
Q
Describe the structure of cortical nephrons.
A
- Cortical nephrons → glomeruli are located in the outer cortex, and have SHORT loops of Henle, that penetrate only a short distance into the medulla.
- Vascular structures of the cortical nephrons differ to the juxtamedullary → the entire tubular system is surrounded by an extensive network of peritubular capillaries.
7
Q
Describe the structure of juxtamedullary nephrons.
A
- LONG loops of Henle that dip deeply into the medulla.
- The vascular structure:
- Long efferent arteriolesextend down into the outer medulla and then divide into specialisedperitubular capillaries→the vasa recta → that extend downward into the medulla, lying side by side with the loops of Henle.
- As with the loop of Henle, the vasa recta return toward the cortex and empty into cortical veins → this specialisd network of capillaries in the medulla plays an essential role in the formation of highly concentrated urine.
8
Q
Describe glomerular filtration.
A
- ~180L / day is filtered in the Bowman’s capsule → most of this filtrate is reabsorbed, leaving ~1L fluid excreted each day.
- The high glomerular filtration rate depends on a high rate of renal blood flow, as well as the special properties of the glomerular capillary membranes.
- GFR → is ~20% of the renal plasma flow and is determined by:
- The balance of hydrostatic and colloid osmotic forces acting across the capillary membrane.
- The capillary filtration coefficient (Kf) → the product of the permeability and filtering surface area of the capillaries.
- The glomerular capillaries have a MUCH HIGHER rate of filtration that most other capillaries because of a high glomerular hydrostatic pressure and a large Kf.
- GFR is ~125ml/min OR 180L/day.
9
Q
Describe the structure of the glomerular capillary membrane.
A
- Glomerular capillary membrane is similar to that of other capillaries, except that it has 3 (instead of 2) major layers:
- The endothelium (innermost) layer.
- A basement membrane.
- A layer of epithelial cells (podocytes) surrounding the outer surface of the capillary basement membrane.
10
Q
Describe the structure of the glomerular capillary endothelium.
A
-
Fenestrated → they are relatively large fenestrae.
- Endothelial cell proteins are negatively charged → they repel the passage of plasma proteins.
11
Q
Describe the structure of the basement membrane of the glomerular capillaries.
A
- Consists of a meshwork of collagen and proteoglycan fibrillae that have large spaces through which large amounts of water and small solutes can filter.
- The basement membrane effectively prevents the filtration of plasma proteins.
12
Q
What are podocytes?
Describe them.
A
- Epithelial cells line the outer surface of the glomerulus → these cells are not continuous, but have footlike processes (podocytes) that encircle the outer surface of the capillaries.
- Podocytes have slit pores through which the glomerular filtrate moves.
- The epithelial cells also have negative charges, providing additional restriction of the filtration of plasma proteins.
- Allows free passage of solutes up to ~60kDa.
- Opposes movement of cells and large proteins.
- Negatively charged molecules are filtered less easily than positively charged molecules.
13
Q
- What comprises:
- Renal blood flow?
- Renal plasma flow?
A
- Renal blood flow = the total volume of blood that transverses the renal artery or vein per unit time = 1100ml/min.
-
Renal plasma flow = the total volume of plasma that transverses the renal artery or vein per unit time.
- Haematocrit = 45%
- RPF = 55% x 1100
- = 600ml/min.
- Intra-renal differences may occur between nephrons in the cortex and medulla and change with hydration state.
14
Q
How do the kidney tubules produce filtrate?
A
- There is a balance of pressures → Starling’s forces.
- States that fluid movement due to filtration across the wall of a capillary is dependent on the balance between the hydrostatic pressure gradient and the oncotic pressure gradient across the capillary.
-
Favouring movement into the tubule:
- Glomerular hydrostatic pressure of the blood → +55mmHg.
- Bowman’s capsule colloic oncotic pressure of the tubule → 0mmHg.
-
Opposing movement into the tubule:
- Bowman’s capsule hydrostatic pressure of the TUBULE (-15mmHg).
- Glomerular capillary colloid oncotic pressure of the BLOOD (-30mmHg).
15
Q
What is autoregulation of glomerular filtration?
A
- Autoregulation mechanisms → intrinsic or local control → enables the kidneys to maintain a relatively constant GFR and to allow precise control of renal excretion of water and solutes.
- There are 2 mechanisms:
- Myogenic mechanism
- Tubuloglomerular feedback (nephrogenic)
16
Q
Describe the myogenic mechanism of the autoregulation of glomerular filtration.
A
- The ability of the individual blood vessels to resist stretching during INCREASED arterial pressure.
- Individual vessels throughout the body (especially small arterioles) have been shown to respond to increased wall tension by contraction of the vascular smooth muscle.
- Prevents excesive stretch of the vessel and also raises vascular resistance.
- Individual vessels throughout the body (especially small arterioles) have been shown to respond to increased wall tension by contraction of the vascular smooth muscle.
- It is thought that the myogenic mechanism may be important in protecting the kidney from hypertension-induced injury → sudden increases in BP cause the afferent arteriole to constrict → attenuating the transmission of increased arterial pressure to the sensitive glomerular capillaries.
- Control of GFR:
- Major changes to blood flow / pressure
- Afferent arteriole dilation → increases GFR
- Efferent arteriole dilation → decreases GFR
- In reality, both happen at the same time.
- Renal blood flow:
- 1-1.2L/min (20-25% of CO) → renal blood flow is essentially constant over a wide range of blood pressure, hence, GFR is essentially constant over a wide BP range.
24
Q
Describe tubular reabsorption and excretion.
A
- Unlike glomerular filtration → tubular reabsorption is HIGHLY selective.
- Glucose and amino acid reabsorption is almost complete, so excretion is ZERO.
- Many ions e.g. sodium, chloride and bicarbonate are also highly reabsorbed, but their rates of reabsorption and thus excretion are highly variable and controlled.
- Waste products e.g. urea and creatinine → poorly absorbed and EXCRETED in large amounts.
- Thus, controlling the rate at which the tubules REABSORB different substances independently of one another permits the control of body fluid composition.
25
Q
Describe tubular reabsorption of water and solutes.
A
-
Active transport
- Active transport → can move a solute against an electrochemical gradient and REQUIRES energy derived from metabolism → it needs a pump that uses ATP.
- Tubular cells are an example of this → the transport of sodium through the tubular epithelia.
- The sodium-potassium pump transports sodium from the INTERIOR of the cell across the basolateral membrane, creating a LOW INTRACELLULAR [sodium] and NEGATIVE intracellular electrical potential.
- This causes sodium to diffuse from the tubular lumen into the epithelial cells through the BRUSH BORDER.
-
Secondary active transport → simultaneous facilitated diffusion
- 2 or more substances interact with a specific membrane protein (carrier molecule) and are transported together across the membrane.
- As one of the substances diffuses DOWN ITS electrochemical gradient (e.g. sodium), the energy RELEASED is used to drive another substance (e.g. glucose) against its electrochemical gradient.
- SGLT - sodium glucose co-transporter.
- NHE → Na+ and H+ exchanger → excrete H+ to make acidic urine and reabsorb Na+.
- Basolateral Na+-K+ ATP pump is generated the Na+
26
Q
Describe the primary transport in the proximal tubule.
A
- 65% of filtered load of Na+ and water are reabsorbed here.
- PCT has a high capacity for reabsorption with highly metabolically active cells.
- Lots of co-transport
- Secretion also occurs
- Organic acids / bases
- Metabolic products
- Drugs and toxins
27
Q
Describe the cellular ultrastructure and transport characteristics of the loop of Henle.
A
- 20% of filtered water and 25% of filtered sodium, chloride and potassium are reabsorbed.
- Thin descending segment → permeable to water.
- Ascending limb → impermeable to water.
- Thick ascending limb → has active transporters and absorbs NaCl and potassium.
- Other ions are absorbed too.
- Co-transporters are important here.
28
Q
Describe the mechanisms of sodium, chloride and potassium transport in the thick ascending limb.
A
- The sodium-potassium ATPase pump in the basolateral membrane maintains a low intracellular [Na+] and NEGATIVE electrical potential in the cell.
- The 1-sodium, 2-chloride, 1-potassium co-transporter in the luminal membrane transports these 3 ions from the tubular lumen (filtrate) into the cells, using the potential energy released by diffusion of sodium DOWN an electrochemical gradient into the cells.
- Sodium-hydrogen counter-transporter → also transports sodium from the tubular lumen (filtrate) into the cell.
- The positive charge (+8mV) of the tubular lumen relative to the interstitial fluid FORCES CATIONS (repels) such as Mg2+ and Ca2+ to diffuse from the filtrate into the interstitial fluid via the paracellular (between the epithelial cells) pathway.
29
Q
Describe the characteristics of the early and late distal tubule.
A
- 5% of the filtered load of sodium is reabsorbed here.
- It is impermeable to water.
- Pumps / absorbs sodium, chloride and potassium just like the thick ascending limb.
- Urine becomes MORE DILUTE.
- The late section of the distal convoluted tubule has 2 cell types:
- Principal cells → absorb water and sodium ions.
- Intercalated cells → absorb potassium and secrete H+ ions.
30
Q
Describe the mechanism of NaCl transport in the early distal tubule.
A
- From the filtrate, Na+ and Cl- are co-transported by the sodium-chloride co-transporter into the tubular cell.
- Sodium is ACTIVELY pumped out at the basolateral membrane by the sodium-potassium ATPase.
- Chloride DIFFUSES into the interstitial fluid via the chloride channels.
31
Q
Describe the mechanism of NaCl transport in the late distal and CORTICAL collecting ducts.
A
- Principal cells → sodium REABSORPTION and potassium SECRETION depend on the activity of the sodium-potassium ATPase on the cell’s basolateral membrane.
- The pump maintains a low intracellular [Na+] → this favours sodium diffusion into the cell through the Na+ channels on the apical membrane.
- Secretion of potassium → high intracellular [K+] → K+ ions then diffuse down their concentration gradient across the apical surface and into the tubular lumen (filtrate) for excretion in the urine.
32
Q
Describe the characteristics of medullary collecting ducts.
A
- Absorbs LESS than 10% of filtered water and sodium ions.
- It is the final site for processing urine - medullary collecting ducts determine URINE OUTPUT and COMPOSITION.
- It is vital for producing dilute or concentrated urine.
- The medullary collecting ducts are impermeable to water unless ADH is present.
- They are permeable to urea and has urea transporters A1 that are activated by ADH.
- Medullary collecting duct is capable of secreting H+ ions against a large concentration gradient, as also occurs in the cortical collecting tubule → plays a role in acid base balance.
34
Q
Describe the role of aldosterone.
A
- It is released from the adrenal cortex - important regulator of sodium reabsorption and potassium EXCRETION.
- Major target of aldosterone is on the principal cells of the cortical collecting duct.
- Stimulates basolateral sodium-potassium ATPase - i.e. more sodium reabsorption and increased potassium excretion.
- Aldosterone also increases the sodium permeability of the apical (luminal) side of the principal cell.
- Aldosterone stimulates the apically located H+-ATPase in the intercalated cells, resulting in proton secretion.
36
Q
Describe the role of anti-diuretic hormone.
A
- ADH increases the water permeability of the DCT, collecting tubule and collecting duct (+ increased urea permeability in the medullary collecting ducts).
- In the absence of ADH, the permeability of the distal tubules and collecting ducts to water is low.
- ADH binds to specific V2 receptors → signal transduction mechanisms → stimulates the movement of a vesicular-associated intracellular water channel (aquaporin 2) to the apical (luminal) surface.
- This is reversible to allow control of water permeability of these distal sections of the tubule.
