Renal Flashcards
Major renal functions
Regulation of water and electrolyte balance.
Hydrogen ion regulation (long term regulation of pH)
Excretion of wastes (metabolic and bio active substances)
Regulation of arterial blood pressure
Regulation of RBC production due to release of EPO
Regulation of vit D production
Gluconeogenesis
Anatomy of kidneys and urinary system
Medulla (external surface)
Cortex (internal surface, houses nephrons, urine drains into renal pelvis and down into ureter)
Parietal fat is protective mechanism
Renal corpuscle:
- glomerulus- bed, tuff of capillaries
- Bowmans capsule- surround glomerulus for protection
Proximal tubule- high reabsorption
Descending limb/ ascending limb (loop of Henle)
Collecting duct- more towards bladder
Vascular elements of kidneys
Two sets of capillaries: glomerular capillaries, peri tubular capillaries
Unique blood vessel arrangement: renal artery- small arteries- afferent arterioles- glomerulus (capillaries) - efferent arterioles- peri tubular capillaries / vasa recta- veins
Nephron function
Glomerulus supplied blood by an afferent arteriole
Renal corpuscle forms a plasma derived fluid filtrate
Around 20% of plasma volume filters into capsule, remaining blood leaves the glomerulus by the efferent arteriole
Filtration barrier ensures filtrate is free of cells and most proteins
Filtrate leaves Bowmans capsule and enters the tubule
Fluid reaching end of nephron combines in the collecting ducts
Fluid drains from end of collecting duct into renal pelvis which is continuous with the ureter
Renal processes
Glomerular filtration
- filtration of fluid from plasma
- initial filtrate has same composition as plasma but does not contain cells and most plasma proteins
Once in nephron tubule, filtrate composition adjusted by:
- tubular reabsorption: movement of substances from tubule to peritubular capillary plasma
- tubular secretion: movement of substances from peritubular capillary plasma to tubule
Purpose of filtration
- clears body of wastes and foreign substances rapidly
- allows constant and rapid adjustments to maintain individual substance balance (eg. Maintain ion levels at set point)
- retain 100% glucose
- 50% urea
- more secretion than filtration of penicillin (try to get rid of drugs)
Nephron filtration
- osmolarity in glomerulus is the same as plasma, but decreases at the end of loop of Henle to ~100- higher the osmolarity, the higher the urine concentration
- bulk of reabsorption occurs in proximal tubule all the way up to Distal tubule
- collecting duct is where fine tune filtration occurs
Renal blood flow
Kidneys receive 1L/ min
All of this blood flows through glomeruli in cortex. The vast majority continues on via efferent arterioles to peritubular capillaries in cortex and then into renal venous system.
The vasculature of the cortex is unusual due ton2 sets of arterioles and 2 sets of capillaries
Renal blood flow
RBF = change in pressure / resistance
R varied by changing arteriolar radii. Normally afferent and efferent are equal, but not always.
If either afferent or efferent constrict- decreased RBF
If either afferent or efferent dilate- increased RBF
Glomerular filtration barriers
Filtration structures; renal corpuscles (glomerulus and Bowmans)
Filtrate composition = plasma, except filtration barrier prevents entry of RBC and proteins.
3 layers: fenestrated capillaries, basement membrane, podocytes- foot processed extensions
Each of these surfaces is neg charged so prevents entry of neg, LARGE charged proteins
Glomerular filtration rate
Favouring filtration:
-Pgc (glomerular capillary BP) chief force pushing fluid across filtration membrane. Varied to control GFR
~55mmHg
Opposing filtration:
- piegc- osmotic force due to protein in plasma ~30mmHg
- Pbs - fluid pressure in Bowmans space ~15mmHg
Therefore net filtration pressure is 15
Regulation of GFR: autoregulation
An intrinsic mechanism that constricts/ dilates afferent arterioles to offset and rise/ fall in BP and prevent change in Pgc
- important to maintain GFR and prevent damage to structures
When BP increases, GFR does not change from 80-180mmHg- kept constant in this range
Autoregulation: myogenic mechanism
- vascular smooth muscle tends to contract when stretched (stretch sensitive ion channels open- depolarisation- voltage gated Ca2+ channels open- Ca2+ contracts smooth muscle
- if BP increases, afferent arterioles constrict and restrict blood flow into glomerulus, restricting increases Pgc and increases GFR
- if BP decreases, afferent arterioles dilate and promote blood flow into glomerulus, restricting decreases Pgc, decreases GFR
Tubuloglomerular feedback mechanism
Local control pathway in which fluid flow through the nephron tubule influences GFR
Directed by macula densa cells (salt detectors)
- as filtration rate in an individual nephron increases, increased NaCl that escapes reabsorption (insufficient time). Increased filtrate (NaCl). Macula densa cells increase NaCl of filtrate and release a vasoconstrictor chemical. Vasoconstriction of afferent arteriole reduced Pgc and therefore GFR decreases
Extrinsic control of GFR
Local controls for GFR can be overridden my sympathetic nerve fibres of autonomic NS due to importance of kidneys in maintaining arterial blood pressure.
Tubular reabsorption
Some solutes and water move into and out of epithelial cells (transcellular transport). Other solutes move through junctions bw epithelial cells (paracellular pathway).
- Na+ reabsorbed by active transport
- electrochemical gradient drives anion reabsorption (Cl-)
- increased osmolarity of ECF decreases osmolarity of filtrate
- permeable solutes are reabsorbed by diffusion through membrane transporters or by the paracellular pathway. Therefore Na+ is the driving force
Transport maximums: saturation of carriers
Diabetics can have glucose in urine. High level of blood glucose- more in filtrate - require specific transporters. If too much glucose, not enough transporters.
Reabsorption of Na+, Cl- and water
- Reabsorption of Na+ is mainly active, transcellular process driven by Na+/K+ATPase pumps in the basolateral membrane
- Reabsorption of Cl- is both passive (paracellular) and active (transcellular), but id couple with the reabsorption of Na+ (due to electrical gradient created by Na+ reabsorption)
- Reabsorption of water is by osmosis and is secondary to reabsorption of solute (particularly NaCl), if water directly followers Na+ - coupled
Movement of Na+ into tubular epithelial cells
- Intracellular concentration of Na+ is lower than extra cellular.
Na+ moving down its electrochemical gradient uses SGLT protein to pull glucose into the cell against its concentration gradient. - Glucose diffuses out of the basolateral side of the cell using the GLUT protein
- Na+ is pumped out by Na+k+ ATPase
Various mechanisms of this Na+ downhill movement across luminal membrane exist. Luminal entry mechanism varies from segment to segment (of nephron tubule) depending on which channels and/ or transport proteins are present
How does water cross tubular epithelium
Three possible routes:
- simple net diffusion through the lipid bolster
- through aqua pores in plasma membrane
- through tight junctions in cells (paracellular movement)
Amount of H2O reabsorption depends on osmotic gradient and the H2O permeability of the region
Tubular reabsorption: proximal tubule
-65% of sodium and chloride reabsorbed here
- virtually all nutrients reclaimed
- cations reclaimed
- bicarbonate
Osmolarity of filtrate at the end of proximal tubule remains at 300mOsM due to Iso-osmotic volume reabsorption (equal portions of solute and water reabsorption)
High surface area
Tubular reabsorption: loop of Henle
Na+ and water NOT coupled
Descending limb: water only, less reabsorbed than solute reabsorption in ascending Limb.
Ascending limb: reabsorption of Na+ (active transport) and other solutes but NOT H2O (not water permeable)
Filtrate at end of loop is hypoosmotic (~100mOsM). Medullary interstitium is hyper osmotic (up to 1200mOsM surrounding juxtamedullary nephrons). Vital to the ability to form dilute or concentrated urine.
Tubular reabsorption: distal tubule and collecting ducts
- by the time filtrate reaches distal tubule, 90% of NaCl and 75% of water originally filtered already reabsorbed
- most reabsorption from distal regions of DVT onwards depends on body’s requirements (at the time) and is regulated by hormones
Kidney concentrates urine
ADH secreted into blood from brain- targets collecting ducts of kidney - if no ADH- water is not permeable to membrane.
ADH binds to receptor on luminal membranes- activates pathway to allow aqua pores to be inserted in luminal membrane of collecting ducts, therefore increased ADH means increased water reabsorption.
This is able to occur due to large osmotic gradient caused by hyperosmotic medullary interstitial fluid
The renal countercurrent multiplier
Comprised of loops of Henle of juxtamedullary nephrons and vasa recta. Long loops of Henle create the osmotic gradient
The vasa recta preserve the gradient and reclaim water.
The collecting ducts use this gradient to adjust urine concentration.
Direction of fluid in loop of Henle is opposite to blood flow in vasa vecta.
Counter current exchanger - exchange bw filtrate in lumen and blood flow in vasa recta.
Water being transferred from descending to ascending vasa vecta, as moves in ECF due to saltiness- but then moves back into ascending limb
Renal control of Na+ and water excretion
- maintain body fluid volume
- maintain osmolarity
- maintain arterial BP
Regulation of blood pressure effectors: - heart
- peripheral arterioles (peripheral resistance)
- large veins
- kidneys (vary output of salt and water)
Change in arterial pressure speeds
Fast- baroreceptors (cardiac and vascular actions). Restoration of pressure within seconds
Intermediate- renal actions (peripheral resistance) - restoration of pressure in minutes
Slow- prolonged renal actions (exertion of salt and water) restoration in hours to days
Arterial pressure change, vascular resistance
Kidneys have baroreceptors (intrarenal baroreceptors)- part of kidneys granular cells (located around afferent arterioles) which sense renal afferent arteriolar pressure.
Juxtaglomerular cells secrete renin into blood.
Triggers renin angiotensin system (RAS), impacts on vasculature and blood volume.
- liver constantly produced angiotensinogen in plasma
- renin cleaves off portion of angiotensinogen to form angiotensin 1 (small peptide)
- encounters angiotensin converting enzyme, converts AGN1 to AGN11 in plasma
- increased BP in a few ways
Stimulation of production of renin
- decreased BP directly signals granular cells of afferent arteriole to produce renin
- decreased BP signals CV control centre, increases sympathetic pathway, causes granular cells of affairs to arterioles to produce renin
- decreased BP causes decreased GFR, decreases NACL across macula densa of distal tubule - stimulates paracejnes and then granular cells
Decreased BP increase renin
- Activity of renal sympathetic nerves- part of cardiovascular baroreceptors reflex- thus there is tight coordination between short and intermediate reflexes
- Detect decrease in afferent arteriolar BP
- Decreased NACL in macula densa cells due to decreased GFR due to drop on BP
Long term renal control of blood volume
- adjustment to GFR and thus conservation of body fluid
Direct effect of decreased arterial BP: lower than autoregulatory limit- decreased glomerular capillary blood pressure, decreased GFR, decreased excretion of sodium and water - adjustment to NA reabsorption by aldosterone - increased NA reabsorption from distal region of Doral tubule and cortical ducts. NA reabsorption increases water retention (must be permeable) and blood volume - increased blood vol increases pressure (stimulated by ANG2) - aldosterone is lipid soluble- induced gene expression and protein synthesis of NA/K channels/
pumps (basolateral membrane) acts slowly. Increases NA reabsorption and K secretion - adjustment to water reabsorption by ADH- caused by plasma osmolarity and reduced blood pressure - more water to reclaim: ADH increases permeability of collecting ducts, allows increased water reabsorption for increased blood vol
Pharmacological manipulation of RAS
- ace inhibitors
- angiotensin 2 by blocking recent sites on target tissue
Renal response to increased plasma osmolarity
Osmolarity is monitored by osmoreceptors found in hypothalamus
If plasma osmolarity exceeds 280mOsm:
- osmoreceptors trigger posterior pituitary to secrete ADH into circulation
- increased plasma ADH
- increased collecting duct water permeability (insertion of aquaporins in luminal membrane)
- increased water reabsorption by collecting ducts (via osmosis due to hyperosmotic medulla)
- therefore decreased plasma osmolarity and urine low in volume, concentrated
