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![MEASUREMENT OF GFR
• Clearance is the tool
• Compound non toxic without reabsorption or secretion
• Creatinine is not ideal[secretion and extra renal elimination]
• Others ;cystatin C inulin
45](https://image.slidesharecdn.com/renalphysiologyi-241014071746-f80a8576/85/Renal-physiology-and-clinical-application-45-320.jpg)
![MEASUREMENT OF GFR
• Clearance is the tool
• Compound non toxic without reabsorption or secretion
• Creatinine is not ideal[secretion and extra renal elimination]
• Others ;cystatin C inulin
45](https://image.slidesharecdn.com/renalphysiologyi-241014071746-f80a8576/75/Renal-physiology-and-clinical-application-45-2048.jpg)
![Renal_Phsyiology_2021_INTRODUCTION[1].pptx](https://cdn.slidesharecdn.com/ss_thumbnails/renalphsyiology2021introduction1-240913164449-bc60bf41-thumbnail.jpg?width=600ounds&width=560&fit=bounds)
Renal physiology and clinical application
- 1. RENAL PHYSIOLOGY PRESENTOR :Dr. Gokula Krishnan
- 2. ANATOMY : • Kidneysare a pair of excretory organs located in the retroperitoneal space against posterior abdominal wall, extending from upper border of T12 to L3 vertebra • Right kidney is slightly lower than the left
- 3. NEPHRON : • Fundamentalunit of kidney, 1.2 million in each kidneys • Receives 20% of cardiac output and responsible for 7% of total body O2 consumption • Outer cortex - 85% - 90% of RBF • Inner medulla – 6% RBF SEVERE HYPOXIA – despite adequate total RBF – Medullary thin ascending limb is vulnerable
- 4. CORTICAL NEPHRON : Malphigiancorpuscles - located in outer cortex Short loop of Henle, penetrating only outer medulla 85% of nephrons Glomerulus and vasa recta - small Major function - Excretion JUXTAMEDULLARY NEPHRON : Malphigian corpuscles - located close to renal medulla Long loop of Henle, extending deep into renal medulla 15% of nephrons Glomerulus and vasa recta - large Major function - concentration or dilution of urine
- 8. GLOMERULUS/RENAL CORPUSCLE • Thebasic structure is a capillary knot fed by the afferent and drained by the efferent arterioles • It contains mesangial cells for structural support and are capable of contracting to modify the capillary surface area available for filtration • They are also phagocytic.
- 10. ● The basementmembrane is a continuous layer of Type IV collagen, laminin and fibronectin which are all negatively charged ● It filters according to molecular size, charge and shape ● Podocytes have foot projections known as pedicels and they interdigitate (like a sieve) for further control of filtration
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- 13. PHYSIOLOGY • Regulation ofintravascular volume, osmolality • Acid-base and electrolyte balance • Excretion of end products of metabolism and drugs • Endocrine functions – fluid homeostasis - bone metabolism - hematopoiesis
- 14. FORMATION OF URINE •GLOMERULAR FILTRATION • TUBULAR REABSORPTION • TUBULAR SECRETION
- 15. GLOMERULAR FILTRATION : •Dependent on balance of Starling forces • Pressure difference between afferent and efferent arterioles
- 16. FILTRATION PROCESS • GFRis around 125ml/min or 180 L/day • The molecular size is the main determinant of particulate filtration • Only molecules below 7kDa are freely filtered with the upper limit of 70kDa • Due to the negative charge of the basement membrane, negatively charged molecules have a reduced rate of filtration
- 17. FILTRATION FORCES • Thefluid movement is dependent on the balance between hydrostatic pressure (Pc) and plasma oncotic pressure (πC) • Compared to normal vascular beds, pressure drops less in afferent arterioles allowing a high Glomerular capillary pressure (PG) of 45 mmHg • As bowman’s capsule is a blind ended tube, there is a hydrostatic pressure (PB) which opposes the (PG) at 10mmHg as well as an initial capillary oncotic pressure (πG) of 25mmHg – this increases as filtration proceeds to make protein more concentrated.
- 19. • The hydrostaticpressure falls further in efferent arterioles so that the peritubular capillary hydrostatic pressure (PPC) is low and reabsorption can occur • The peritubular capillary oncotic pressure (πPC) is 35mmHg and falls as more fluid is reabsorbed • Overall: GFR α PG – (PB + πG) • For conversion to real measurements, the filtration coefficient (Kr) is introduced which is a product of glomerular capillary permeability and filtration surface area: • GFR = Kr x (PG – (PB + πG))
- 20. • Normal GFR– 125ml/min 180 L/day
- 21. MEDIATOR CONTROL OFGFR :
- 22. Alpha – adrenergiceffect • Afferent and efferent arterioles have pressure dependent ability to contract or relax • Prevents pressure diuresis when BP is elevated • Mild alpha stimulation – constriction of efferent arterioles • Severe alpha stimulation – constriction of both afferent and efferent arterioles – decreases filtration fraction
- 24. The juxtaglomerular apparatus Includingmacula densa, extraglumerular mesangial cells, and juxtaglomerular (granular cells) cells 24
- 25. Renin-Angiotensin-Aldosterone System Fall inNaCl, extracellular fluid volume, arterial blood pressure Juxtaglomerula r Apparatus Reni n Live r Angiotensinoge n + Angiotensin I Angiotensin II Aldosteron e Lung s Convertin g Enzyme Adrena l Cortex Increased Sodium Reabsorptio n Helps Correc t Angioten sinase A Angiotension III Efferent arteriolar constriction 25
- 26. RENIN ANGIOTENSIN ALDOSTERONESYSTEM • AT II – potent vasoconstrictor of efferent arterioles + afferent arterioles • AT II stimulates 2 pathways with opposing effects • AT1 receptor – on luminal epithelial surface of PTC, mTAL, macula densa, distal tubules & CD • AT II – AT1 R vasoconstriction, reabsorption of Na & water • AT II – AT7 R vasodilatation – NO, PG • Negative feedback mechanism
- 28. VASOPRESSIN Potent vasoconstrictor ofefferent arteriole Unlike catecholamines and AT II, it has little effect on afferent arterioles Stimulus - Hyperosmolarity, Hypovolemia V1A R - blood vessels, mesangial cells, vasa recta Vasoconstriction 🡪 V2 R – medullary collecting duct AQ-2 channels Water reabsorption
- 30. • Surgical stimulation– major stimulus for AVP secretion • Mediated by pain or by intravascular volume changes – lasts for at least 2 to 3 days after procedure
- 31. ALDOSTERONE • Secreted byZona Glomerulosa of adrenal cortex • Stimulus – Hyperkalemia, Hyponatremia, AT II, ACTH • Acts on TAL, principal cells of distal tubules, collecting ducts • Delay of 1-2 hours from its secretion to action
- 32. • Increase absorptionof sodium and water from GI & sweat gland • Increased renal Na+ reabsorption primarily in the cortical collecting duct • Increased K+ secretion (with H+) • Increased ATPase synthesis and activity in tubular cells
- 34. DOPAMINERGIC SYSTEM • DA1R – renal and splanchnic vasculature, PCT VD, natriuresis, 🡪 diuresis • Dopamine inhibits Na-H antiport in PCT and Na-K ATPase pump in mTAL – inhibits NaCl reabsorption • D2 R – on pre-synaptic nerve terminal of post-ganglionic sympathetic nerves inhibits release of Norepinephrine associated vasodilatation
- 35. NATRIURETIC PEPTIDES • Keyproteins cause vasodilatation by blocking receptors to action of NE and AT II • ANP – Atrial wall stretch • BNP – ventricle stretch • CNP – endothelium of major blood vessels
- 36. • Promotes afferentarteriolar dilatation with or without efferent arteriolar constriction, inhibits endothelin, renin, decrease AT II mediated aldosterone • Inhibits AVP secretion diuresis • Important in oliguric patients to increase Urine output
- 37. PROSTAGLANDINS Systemic hypotension, Renalischemia, NE, AT II, AVP PG D2, E2, I2 VASODILATATION NSAIDs – inhibit this compensatory mechanism – medullary ischemia – by inhibiting PG synthesis
- 38. Regulation of renalblood flow Autoregulation • Autoregulation normally occurs between mean arterial pressures of 70 and 130 mm Hg • Blood flow is generally decreased at MAP < 60 mm Hg • Glomerular filtration normally ceases when the mean systemic arterial pressure is < 40-50 mmHg
- 39. Intrinsic : myogenic mechanism Tubuloglomerularfeedback mechanism Extrinsic : Sympathetic Nervous System Renin angiotensin aldosterone system
- 40. MYOGENIC REGULATION : Autoregulation- intrinsic myogenic response of afferent arterioles to changes in pressure
- 41. TUBULOGLOMERULAR FEEDBACK • Singlenephron GFR (SNGFR) is greatest in the juxtamedullary nephrons • SNGFR is influenced by the distal tubular fluid composition which is influenced by GFR. • The feedback mechanism has 3 components: 1. Tubular fluid characteristic is recognised by the tubular epithelium i.e. increased Na+ 2. Signal is transmitted to the glomerulus i.e. increased Adenosine and ATP 3. An effector mechanism alters the GFR i.e. afferent arteriolar vasoconstriction
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- 45. MEASUREMENT OF GFR •Clearance is the tool • Compound non toxic without reabsorption or secretion • Creatinine is not ideal[secretion and extra renal elimination] • Others ;cystatin C inulin 45
- 46. •MDRD 1999 (modificationof diet in renal diseases) GFR= 186 × SCr -1.154 ×age-0.203 ×(0.742 if female)×(1.21 if black) •Cockcroft Gault equation CrCl (ml/min)=(140- age )×lean body weight ×( 0.85 female) S.Cr (mg/dl)× 72 IN CKD MDRD BETTER THAN CG Many false positives GFR declines with age GFR has to be adjusted to body surface areas 46
- 47. GFR in AKI •Estimated GFR may under or over estimate AKI • Initial raise in creatinine and drop GFR reversible by fluids • So when affected pathologically it is irreversible after long time • There is increase in fraction of Na excreted and reduction in urine osmolality 47
- 48. • AKI onCKD cannot be quantitated by S . Creatinine • Normal SCr 1 to 3 increase has GFR 120 to 30 drop • Scr 2.5 to 5 has GFR drop from 40 -20 • So confusing to say which has AKI • SO USE RELATIVE CHANGE IN CREATININE • An acute rise in >0.3 creat can be considered AKI on CKD 48
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- 52. LOOP OF HENLE •Originates in the renal cortex and passes into the medulla • Only juxtamedullary nephrons (15%) have long loops that pass deep into the medulla • There is a small osmotic pressure difference between the ascending and descending limbs of the loop which is multiplied through the flow in opposite directions(countercurrent) • Thin descending limb is permeable to water and all ions. • Ascending limb is impermeable to water • Thick part only can extrude ions
- 54. • Therefore, thefluid in the ascending limb osmolality will be lower than that in the interstitial tissues • The extrusion of ions to interstitium occurs by tubular cells which take place in the basal membrane • The entry through the apical membrane occurs with the Na+/K+/Cl-cotransporter and is extruded through Na+/K+ ATPase activity on the basal membrane • This leads to a build-up of NaCl in the interstitium.
- 55. • Cells onthe ascending limb can sustain an osmotic difference of 200mosmol/kg H2O through ionic extrusion • Fluid flux in both the Convoluted Tubule & the Vasa Rectae contribute to the function.
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- 59. Counter-current Exchange inthe Vesa Recta Preserves Hyperosmolarity of the Renal medulla 59
- 60. ACID BASE REGULATION •HCO3 reabsorbed proximally • The kidneys excrete 1 meq/kg/day of noncarbonic H+ ion • • the intercalated cells of the collecting duct secrete H + ions that are subsequently trapped by urinary buffers, particularly phosphates and ammonia • as the kidneys fail, the level of serum bicarbonate – falls severely, reflecting the exhaustion of all body buffer systems, including bone. 60
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