Urinary Lecture 3.1 Flashcards
State the function of the nephron and which 3 processes allow this function
Regulation of plasma composition.
1) Filtration - forms glomerular filtrate
2) Reabsorption - movement from tubular fluid to blood
3) Secretion - movement from blood to tubular fluid
What are the two main pathways for absorption and secretion in the nephron?
1) Transcellular route - tubular cells, secondary active transport
2) Paracellular route - between cells, concentration gradient, electrical gradient
What two structures make up the filtration unit of the kidneys?
How is the glomerulus adapted for efficient filtration?
Where does the glomerular filtrate get stored before moving into PCT?
Glomerulus + Bowman’s capsule
Fenestrated glomerular capillaries (pores)
High surface area, thin of capillary walls
Visceral layer, (inner layer of Bowman’s capsule in direct contact with glomerulus) direct contact with glomerulus, made up of podocytes
Bowman’s space - area between visceral + outer layers of Bowman’s capsule. Glomerular filtrate collects here before moving to proximal convoluted tubule
Bowman’s space
What three layers make up the glomerular filtration membrane?
Endothelium of glomerular capillaries (innermost). Fenestrated endothelial cells. Blocks cells + large proteins
Glomerular basement membrane: Middle. Dense. -ve charged layers made of proteins (e.g. collagen). Filter, blocks large molecules +ve charged molecules, albumin (SIZE SELECTIVE, CHARGE SELECTIVE BARRIER)
Podocytes: Outermost, specialised cells, make up the visceral layer of Bowman’s capsule. Foot like extensions called pedicels, wrap around capillaries. Spaces between pedicels = filtration slits, restrict passage of large molecules.
What are the two main factors which determine filtration?
Size, charge
Size:
Small substances: <7kDa freely filtered through filtration barrier into urine
Large >70kDa: too big to pass through filtration barrier, retained in blood
Medium: partially filtered
Why aren’t proteins filtered through the glomerular filtration membrane?
What is the main factor which drives the filtration process?
Barrier of basement membrane - PROTEIN FIBRILS THAT FORM BASEMENT MEMBRANE IS MAIN BARRIER
Charge: filtration barrier less permeable to -ve proteins, albumin kept in blood, not filtred out
Hb: small enough to be filtered out, but stays in blood because contained in RBCs
BLOOD PRESSURE
- What is the role of Starling forces?
- Describe the filtration process
- Regulate movement of fluid across capillary membranes
- High glomerular blood hydrostatic pressure forces water + solutes through filtration membrane into Bowman’s space (GBHP)
Filtration process opposed by capsular hydrostatic pressure (CHP) (pressure exerted by filtrate already in Bowman’s space + blood colloid osmotic pressure (BCOP), osmotic pull by proteins in glomerular capillaries)
Net Filtration Pressure (NFP):balance of these pressures determines NFP, which drives movement of fluid from blood into Bowman’s capsule
NFP = GBHP - (CHP + BCOP)
What is the glomerular filtration rate (GFR)?
How is eGFR calculated?
Filtration formed per minute
GFR = NFP x Kf (usually 125 ml/min)
Estimated GFR
Simple blood test for Serum creatinine
Patient factors need to be considered, age, sex, race
Why is creatinine important when measuring GFR?
Creatinine is a waste product created by muscle metabolism
Released into blood
Freely filtered by glomerulus, minimal reabsorbed, therefore, level of creatinine in the blood directly reflect how well kidneys are filtering - concentration of creatinine in blood is a good indicator of kidney function, if a lot is reabsorbed, poor kidney function
What is autoregulation of renal blood flow?
How does autoregulation work?
Blood leaves efferent arterioles via ………. Capillaries
The ……. Is the main site of reabsorption
Kidneys maintain consistent blood flow + GFR, despite changes in BP
Protection of glomeruli from damage due to sudden changes in BP
Afferent, efferent arterioles - afferent arterioles bring blood to glomeruli. Different arterioles carry blood away. Kidneys adjust tone (tightness) of arterioles to regulate blood flow + pressure in glomeruli
Constriction of either = drop RBF (increase vascular resistance)
Constriction of afferent arterioles - less blood into glomeruli. Reduces CHP, decreases GFR.
Constriction of efferent arterioles - blood flow out of glomeruli restricted, increases CHP, increases GFR. More blood being filtered
Peritubular capillaries
PCT
Describe glucose reabsorption in the PCT
SGLT-1 SGLT-2 reabsorb glucose from filtrate back into blood, using energy from sodium gradient
When does glucosuria occur?
Plasma concentration >10mM = more glucose being filtered that reabsorbed, glucose appears in urine
Describe reabsorption of Bicarbonates (HCO3-)
H+ combines with filtered bicarbonates
Forms carbonic acid
Carbonic acid dissociates into CO2 + Water
CO2 diffuses back into PCT cells, where it is converted back into bicarbonates + reabsorbed into blood stream
Describe how kidneys reabsorb sodium (Na+) and water from filtrate
The most water reabsorption occurs through …….
….. Is the most common aquaporin
and is located in ………… of the nephron
Na+
Basolateral Na+/K+ ATPase Pump: This pump is in nephron. Keeps Na+ levels low inside the cell by pumping Na+ out and K+ in.
Na+ moves into cells: Na+ from filtrate moves into cells (down conc gradient)
Water
-Movement of ions / osmotic forces: Na+ moves into cells, then into surrounding spaces (ECF), on peritubular capillary side creating osmotic force. Water naturally follows sodium to balance out concentration, osmotic forces generated
- Pulls water through cell + tight junctions between cells (moderately leaky) (For understanding: Water moves through the cells, follow sodium until ECF, reabsorbed into blood by peritubular capillaries)
PCT
AQP1
PCT
Describe reabsorption and secretion in the loop of Henle
What is the name of the system involved in reabsorption and secretion in the loop of Henle?
Descending limb: Permeable to water not to solutes (AQP1 Channels). Urea + Na+ diffuse into filtrate from medullary interstitium (surrounding tissue)
Thin ascending limb: Impermeable to water, allows passive NaCl reabsorption, Na+/K+/2Cl- cotransport.
Thick ascending limb: Actively transports Na+, K+, Cl- out of tubular fluid. K+ transported back into tubules by ROMK. Cl- transported into tissue fluid via CLC-NKB channels
Filtrate becomes hyperosmotic - loss of solutes but not water. Na+ pumped into interstitial space, makes medulla hyperosmotic
Countercurrent multiplier system
What is renal clearance?
How quickly a substance is removed from the plasma by the kidney and excreted in urine
(If substance is neither reabsorbed / secreted in nephron, renal clearance is same as glomerular filtration rate e.g. insulin, creatinine, Insulin clearance, creatinine clearance, used to estimate GFR)
