Physiology: Renal Flashcards
Define GFR
Volume of fluid filtered from glomerular capillaries into Bowman’s capsule per unit time.
125ml/min (180L/24 hours) 10% less in women
Factors controlling GFR?
- Hydrostatic pressure in capillaries and tubules
- Osmotic pressure gradient (oncotic)
- Size of capillary bed
- Permeability of capillary bed (Mesangial cells contract/relax)
Starling Forces
Starling Forces = K(Hydrostatic pressure of capillaries – hydrostatic pressure of tubules) – (osmotic pressure of capillaries – osmotic pressure of tubules)
K = GF coefficient altered by mesangial cell contraction.
Clinical factors that affect Starling forces
- Renal blood flow
- Systemic BP
- Ureteric obstruction
- Renal parenchymal oedema
- Afferent and efferent arteriolar contraction
- Plasma proteins
Role of Mesangial cells
Contraction decreases area for filtration
Contraction: Noradrenaline and Histamine, ADH, ATII
Relaxation: Prostaglandins, Atrial Natriuretic Peptide, Dopamine
Kidney regulation of urine
- Filtration
- Secretion
- Reabsorption
Measuring GFR
Measure the excretion of a substance, which is freely filtered through the glomeruli – neither secreted nor reabsorbed by the tubule.
Non toxic and not metabolized e.g. insulin
GFR = Ux X V/Px
Ux = concentration of X in urine
V = urine flow/time
Px = Arteriolar concentration of X
How do kidneys deal with K+?
Freely filtered at glomerulus
Actively reabsorbed in PCT
Secreted in distal tubule – rate proportional to flow
Secreted in CT – aldosterone excreted
Factors influence ATII production
ATII is the effector protein in the RAAS – integral to the control of volume regulation
So principally those that influence renin secretion:
Increased secretion
- Increased sympathetic activity
- Increased circulating catecholamines
- Prostaglandins
(from Na+ depletion, diuretics, hypovolaemia, CCF, dehydration, upright posture, renal artery/aortic constriction)
Decreased secretion
- Increased Cl– and Na+ re-absorption
- Increased afferent arteriolar pressure
- Vasopressin (ADH)
Physiological affects of ATII
- Arteriolar constriction
- Directly on adrenal cortex to release aldosterone
- Contraction of mesangial cells causing decreased GFR
- Direct effect on renal tubules to increase Na+ reabsorption
- On the brain to decrease sensitivity to baroreceptors
- Reflex to increase water and increase secretion of ADH and ACTH
Essential feature of the loop of Henle countercurrent multiplex
High permeability of their descending limb to water and active transport of Na+ and Cl– out of thick ascending limb which is not permeable to H2O.
Role
Contributes to osmotic gradient in the medullary pyramids
How does urea reach interstitium?
Transported by urea transporters by facilitated diffusion.
Amount of urea depends on amount filtered which depends on dietary protein.
Describe the way kidneys handle glucose
- Freely filtered
- Reabsorbed in the early part of PCT (by secondary active transport)
- Na+ dependent co-transportation
- Excreted in urine if renal threshold is exceeded.
Potential consequences of glycosuria
Osmotic diuresis = dehydration, electrolyte loss.
What factors influence clearance of substances by the kidneys?
- Amount of substance excreted = amount filtered and net amount transferred
- Changes in renal blood flow and systemic blood pressure
- Active transport (primary and secondary(
- Hormones (aldosterone, angiotensin, endothelial growth factor)
Describe the renal response to acidosis
Kidneys aim to return serum pH to normal by increasing H+ :
- Kidneys retain HCO3– by actively secreting H+
- Renal tubule cells secrete carbonic anhydrase converting CO2 to H+ and HCO3 , then tubule cells secrete H+ in exchange for Na+
- Amount of secreted H+ limited by pH>4.5 but buffering in tubular fluid pH with HCO2, HPO4 and NH3 allows greater H+ secretion
a) Carbonic anhydrase converts CO2 to H+ and HCO3
b) Renal to actively secrete H+ in exchange for Na+
c) HCO3– actively reabsorbed
Urinary buffers:
Bicarbonate (proximal tubule) – HCO3–->CO2 + H2O
Phosphate (distal tubule) – HPO42–> H2PO4–
Ammonia (both) – NH3->NH4+
Metabolic acidosis compensation?
- Respiratory system: Increased ventilation & Decreased PCO2
- Glutamine synthesis in liver in chronic metabolic acidosis -> increased to provide additional source of NH4+ as well as NH3 secretion to increase over days.
By what mechanism is H+ secreted in the distal tubules and collecting ducts of the kidneys?
ATP driven proton pump
Aldosterone acts on this pump to increase H+ secretion
Principal buffering systems in the body?
Blood – Bicarbonate, Protein, Hb
Intracellular – Protein and phosphate
Urine – also uses ammonia
Interstitium – bicarbonate
Body’s response to metabolic acidosis?
- Buffering : in blood, intracellular and interstitial space
- Respiratory response: increased ventilation and excretory CO
- Renal response : Linked to Na+/K+/ATPase
Is there a difference between proximal and distal tubules?
PCT/DCT/CT secrete H+
PCT via Na+/H+ exchange and Na+/K+/ATPase
DCT/CD H+ secretion by ATP driven proton pump.
Factors that increase acid secretion
Increased PCO2, increased PaCO2
Increased aldosterone
Increased calcium concentration, decreased K+ (Increased K+ decreases H+ secretion)
How does the kidney handle K+?
Filtered, reabsorbed and secreted
- Freely filtered at glomeruli (600mEq/day)
- Mostly/largely reabsorbed in proximal tubule by active transport
- K+ is then secreted by passive diffusion in distal tubule.
- Passively secreted in collecting duct
- Total K+ excretion is approximately equal to K+ intake = 90mmol
Factors influencing this? (Kidney handling of K+)
- Rate of K+ secretion is proportional to flow of tubular flow
- Aldosterone increases Na+ reabsorption (primarily in the collecting duct) and therefore promotes K+ secretion
- In distal nephron, K+ and H+ compete for secretion in association with Na+ reabsorption therefore in acidosis, when H+ excretion is increased, K+ secretion decreases
- Inhibition of K+ reabsorption in proximal nephron (e.g. osmotic/loop diuretic) promotes excretion of K+.
How is ascending and descending loops of Henle different?
Thin descending limb is water permeable (due to presence of aquapores) and tubular fluid becomes hypertonic. Thick ascending limb is impermeable to H2O and Na+ is actively transported out, so fluid is more hypotonic (K+ diffuses back passively)
Describe the process of tubuloglomerular feedback in the nephron
This process occurs to maintain the constancy of the load delivered to the distal tubule. The macula densa in the ascending limb of the loop of henle sense the rate of flow and feeds back to either increase of decrease the rate of filtration in the glomerulus.
Please outline the structure of the LOH
- Thin/descending, Thick/Ascending – situated mostly in the medulla
- Origin from PCT
- Short and long loops
- Macula densa at distal end, where it joins the DCT.
Can you draw a nephron and describe functions of each part
Glomerulus – Filtration (afferent and efferent arterioles)
PCT – reabsorption of sodium, glucose, amino acids and bicarbonate
Descending limb – then, H2O permeable
Ascending limb – site of the Na+K+2Cl – generates concentration gradient
DCT – Na+K+Cl– pump–
CD: under control of ADH and aldosterone
Cell types in Glomerulus – cap endothelial cells fenestrated with 70-90nm pores
Epithelial cells of Bowman’s capsule – Podocytes possess pseudopodia that form filtration slits once capillary epithelium
What properties of substances in blood prevent free passage across glomerular membrane?
- Large diameter >8nm
2. Lack of neutrality (charged)
How does RAS respond to hypotension?
Decreased BP leads to renin being released from the JG cells to form angiotensin I -> AT I converted to ATII in lungs by ACE. ATII causes vasoconstriction and decreased secretion of both salt and water.
Other systems affected by RAS
- Sodium and water retention
- Stimulate aldosterone secretion
- Facilitate secretion of noradrenaline
- Downgrade- baroreceptors
- Increase secretion of vasopressin
Major physiological features of acute intrinsic renal failure?
- Loss of urine concentrating and diluting capacity: Polyuria->oliguria->Anuria
- Uraemia : Increased buildup of urine, creatinine and toxins
- Acidosis, anaemia
- Sodium retention, oedema and heart failure
Common finding in urinalysis of intrinsic renal failure
- Leucocytes
- Proteinuria
- Red cells
- Casts
What are urinary casts?
Proteinaceous material precipitated in tubules washed into the bladder.
Neurological pathways in normal micturition
- Spinal reflex: S2+S3+S4 roots. Facilitated/inhibited higher centers; subject to voluntary control (first urge to void at 150ml. Marked fullness at 400ml)
- Micturition reflex – stretch receptors in bladder wall
- Parasympathetic efferent nerves – mediate contractions of detrusor muscle
- Pudendal Nerve (S2,3,4) – voluntary contraction of perineal and external urethral sphincter.
Muscles involved in micturition
- Bladder: Smooth muscle in spiral, longitudinal and circular bundles (Circular bundle = detrusor muscle whose contraction results in involuntary emptying)
- External urethral sphincter – Skeletal muscle: relaxes during voluntary micturition
- Perineal muscles
- In males – urine left in urethra expelled by several contractions of bulbocavernous muscle
- Abdominal wall muscle – contraction aids urine expulsion. NB -> internal sphincter (SM) plays no role.
What prevents vesico-ureteric reflux?
Oblique passage of ureters through bladder wall (i.e. keeps ureters closed during peristaltic waves)
What factors increase renin secretion?
Catecholamines
Sympathetic activity – via renal nerves
Prostaglandins
Role of vasopressin in dehydration
Promotes water reabsorption in CD via aquaporin. It causes vasoconstriction.
Hormones involved in ECF volume maintenance
- Renin
- ATII
- Aldosterone
- Vasopressin
Response of atrial naturetic peptide in response to fluid overload?
Diuresis -> mesangial cells relaxation -> increased GFR -> Increased Na+ secretion from kidneys -> H2O follows
Normal Renal Blood Flow
= 25% of CO (1250ml)
= 1.2-1.3L/min at rest
Mechanisms that determine Renal Blood Flow
- Perfusion pressure (systemic MAP)
- Renal arterial flow – Na+ ATII = constriction, Ach, prostaglandin
- Renal nerves – Sympathetic -> noradrenaline -> decreased renal blood flow
- Autoregulation – duct smooth muscle contraction, MO
- Regional differences in renal blood flow
How do blood flow and O2 extraction vary in different parts of the kidney?
- Cortical flow = high (and O2 extraction low)
- Medullary blood flow = low O2: extraction higher
- Medullary is vulnerable to hypoxic damage = if flow is reduced, increased O2 usage
Consequence of sustained reduction of RBF
Renal blood flow maintained at MBP>70
Medulla is vulnerable to hypoxia (high Metabolic Rate)
ATN
Uraemia
Renin INCREASE
1) Sympathetic activity
2) Catecholamines
3) Prostaglandins
Renin DECREASE
1) Increase Na+ and Cl– reabsorption
2) Increased afferent and efferent pressure
3) ATII and vasopressin
NB: Afferent and efferent pressures detected at intrarenal baroreceptors
What conditions increase renin secretion?
- Dehydration, haemorrhage, hypotension, diuretics
- Upright position, psychological stimuli
- CF, hepatic cirrhosis
- Constriction of renal artery, constriction of aorta
- Sodium depletion
How is Na+ handled in the kidney?
- Glomerular filtration
- Actively transported out except in the descending limb of the loop of henle
- Active reabsorption 99% (influenced by aldosterone and ADH)
Mechanisms involved in reabsorption and secretion at renal tubules
Endocytosis
Passive diffusion
Facilitated diffusion
Active transport
Where does Na+ reabsorption occur in the nephron?
All parts except the descending limb of the loop of Henle.
60% PCT primarily
30% thick ascending limb of loop of Henle
7% DCT
3% CT
Mechanisms involved in Na absorption
Na/K ATPase active transport
Mechanisms that decrease sodium excretion:
- Decreased GFR
- Increased tubular reabsorption
– Increased aldosterone
– AT II (PCT)
– Decreased AMP
Vasopressin action on kidneys
Collecting duct -> ADH binds to aquaporin 2 channel inserted to increased H2O permeability
Vasopressin - Drink large amounts of H2O
Begins 15 minutes post and maximum effect in about 45 minutes
Drinking decreases ADH = diuresis
Most inhibition is because of decrease in plasma osmolality
Thirst: An appetite under hypothalamic control
What causes it?
- Increased plasma osmolality – osmoreceptors in anterior hypothalamus
- Hypovolaemia: RAS, barocreptors in heart and blood vessels
- Prandial
Habit, GI, hormone effects - Psychogenic
Dry pharyngeal mucous membranes
Vasopressin actions
1) Retention of H2O
2) Decreased CO
3) Glycogenolysis
4) ACTH secretion from anterior pituitary
Vasopressin secretion is increased by:
1) Osmolality increase
2) ECF volume decrease
3) Pain, nausea, surgical stress, emotion, vomiting, standing, drugs (carbamazepine)
Vasopressin secretion is decreased by:
1) Alcohol
2) Decreased osmolality
3) Increased ECF volume
Water re-absorption:
- 60-70% in PCT
- 15% loop of henle
- 5% DCT
- Up to 10% in CD, depending on presence of ADH
