Renal_Phsyiology_2021_INTRODUCTION[1].pptx

Renal_Phsyiology

1. Renal Physiology Introduction & general functions Dr. Walid Alsharafi UST

2. General Functions Main function is Homeostasis : Produce & expel urine metabolic waste products foreign chemicals (drugs ,food additives) Production of hormones Renin : ↑ during ischemia of kidney → ↑ blood pressure Erythropoietin (EPO): ↓ during ischemia of kidney → anemia Active vitamin D3: ↓ during ischemia of kidney → osteoporosis Glucose Synthesis (gluconeogenesis): The kidneys cortex synthesize glucose from amino acids   and other precursors during prolonged fasting

3. General Functions Main function is Homeostasis : Regulate the volume and composition of the extracellular fluid Control pH Control blood volume & blood pressure Short term : renin- angiotensin system Long term : regulate body fluids. Controls osmolarity and Controls ion balance Osmolarity  (Osm/ L ) is the total concentration of all solutes in the solution per 1 L. Osmolality is the concentration of dissolved particles of chemicals and minerals   per 1 kg of solvent . such as sodium and other electrolytes High osmolality means   more particles in your serum. Lower   osmolality means  they’re more diluted produce prostaglandins

4. Kidney disfunction and homeostasis With acute/ chronic kidney disease, these homeostatic functions are disrupted. With complete renal failure, enough potassium, acids, fluid , and other substances accumulate in the body to cause death within a few days. So, hemodialysis are initiated to restore the body fluid and electrolyte balances.

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6. Renal Physiology Physiologic anatomy of the kidney Renal blood flow Dr. Walid Alsharafi UST

7. Overview of Function Anatomy The System Urinary system consists of: Kidneys Ureters Urinary Bladder Urethra – contain the functional unit of the system Conducting & Storage components

8. Overview of Functional Anatomy The Kidney Kidney is divided into: Cortex (outer ) Granular Full of blood vessels Contain: bowman's capsule, PCT, DCT Medulla (inner) Striated Pale : no or little blood vessels Contain : Loop of Henle , collecting tube Weight : 150g/ each kidney Nephron is located in both the cortex and medullary areas renal pelvis

9. Nephrons Nephrons : are the structural and functional units that form urine. There are about 1 - 1.3 million nephrons per kidney. Two main parts in the nephron: Glomerulus: a groups of capillaries The highest capillary blood pressure in the body = 60mmHg Renal tubules: begins as cup-shaped glomerular (Bowman’s) capsule surrounding the glomerulus

10. Functional Anatomy of The Kidney The nephron consists of: Vascular components Tubular components Tubovascular component

11. Vascular components There are 4 blood vessels: Afferent & efferent arterioles Glomerulus Peritubular capillaries Vasa recta Kidneys receive 22-25% of cardiac output. High hydrostatic pressure in the glomerular capillaries (about 60 mm Hg) causes rapid fluid filtration . low hydrostatic pressure in the peritubular capillaries (about 13 mm Hg) permits rapid fluid reabsorption

12. Approximate Pressures and Vascular Resistances in the Circulation of a Normal Kidney Pressure in Vessel (mm Hg)   Vessel Beginning End Per Cent of Total Renal Vascular Resistance Renal artery 100 100 ∼0 Interlobar, arcuate, and interlobular arteries ∼100 85 ∼16 Afferent arteriole 85 60 ∼26 Glomerular capillaries 60 59 ∼1 Efferent arteriole 59 18 ∼43 Peritubular capillaries 18 8 ∼10 Interlobar, interlobular, and arcuate veins 8 4 ∼4 Renal vein 4 ∼4 ∼0

13. Autoregulation changes in arterial pressure have some influence on renal blood flow. kidneys have effective mechanisms for maintaining renal blood flow and GFR relatively constant over an arterial pressure range between 80 and 170 mm Hg, a process called autoregulation.

14. Tubular components Proximal convoluted tubule (PCT): most of kidney actions occur in PCT due to it has : Longer tube (15mm) and smaller lumen Microvilli in its lumen (Brush border ) to ↑ surface area Plenty of Mitochondria : more active than DCT Distal convoluted tubule (DCT): Shorter tube (5mm) and larger lumen Lack of microvilli

15. Tubular components Nephron loop (loop of Henle): Thin (flat epithelium) : passive part Thick (cuboidal epithelium): active part Collecting duct: - It contains 2 types of cells : Principal cells (P cells): more in number but less important - Function: 1- (Na ,K) exchange by aldosterone 2- H2O reabsorption by ADH Intercalated cells( I cells ): less in number but more important -Function : acid- base balance 1- acid secretion 2- HCO3 reabsorption

16. Tubovascular component Juxtaglomerular apparatus It is the area of contact between afferent and efferent arteriole and DCT Juxtaglomerular apparatus has 3 parts: Macula densa chemo receptor to detect osmolarity Juxtaglomerular cells : in the walls of the afferent and efferent arterioles Secrete renin Lacis cells (Extraglomerular   mesangial cells ) Store renin Secretion of erythropoietin Function: Auto regulation of GFR-RBF of the same nephron

17. Renal blood flow

18. The Nephron The nephrons form urine by 3 steps: Glomerular Filtration Tubular Reabsorption Tubular Secretion

19. The Nephron Locations for : filtration, reabsorption, secretion & excretion

20. First step in urine formation. Filtration at Glomerulus: Water Na + Cl - Bicarbonate K + Glucose Urea Creatinine Uric Acid Nephron Filtration

21. Nephron Filtration Renal arteries: - Transport 1200 mL of blood per minute General factors affecting GFR: Renal Blood flow (RBF) Glomerular capillary hydrostatic   pressure

22. Nephron Glomerular Filtration Glomerular filtration rate (GFR) = 125 ml/min or 180 L/day. Plasma volume is filtered 60 times/day or 2 ½ times per hour. Renal plasma flow=650ml/min filtration fraction = about 20% most of the filtrate contents must be reabsorbed, or we would be out of plasma in 24 minutes!

23. Glomerulus Glomerular membrane has 3 layers : Glomerular endothelium Contains holes : (79-90)nm Basement membrane -ve charges Prevent loss of plasma protein especially albumin Podocyte: Contains pores Loss of podocyte may cause albuminuria

24. Glomerulus Mesangial cells: Location : Present betweem endothelium and basement membrane. Function : Control surface area → control filtration rate Contraction of mesangial cells → ↓ filtration Takes up immune complex During autoimmune diseases of kidney , antibodies is formed against mesangial cells (antigens of kidneys)

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26. Renal Physiology Glomerular filtration rate (GFR) Dr. Walid Alsharafi UST

27. STARLING EQUATITION GFR=  filtration coefficient (KF) × net filtration force KF is constant of filtration KF depends on : Permeability - which depends on : Size of molecules Molecules with < 4 nanometer is easily filtered Charges of molecule - ve charged < + ve charged Only 2-5% of albumin is filtered Loss of – ve charges of basement membrane causes albuminuria Area of glomerular membrane

28. Factors affecting GFR KF : is constant of filtration Permeability ↑ thickness ( such as in diabetes mellitus) → ↓ filtration Surface area Relaxed mesangial cells ↑ → filtration Contracted mesangial cells ( such as DM) → ↓ filtration Hydrostatic pressure Afferent arteriole Dilatation of afferent ↑ → filtration Constriction of afferent ↓ → filtration Efferent arteriole Dilatation of efferent → ↓ filtration Constriction of efferent (usually by angiotensin II) → ↑ filtration Severe or marked constriction of efferent → ↓ renal blood flow → ↓ filtration ABP ABP between 90-200 dose not affect GFR ABP < 90 → ↓ filtration

29. Factors affecting GFR Pressure in Bowman’s capsule ↑ pressure ( impacted stone in ureter ) → ↓ filtration Colloidal osmotic pressure of plasma protein if water ↑ ) when ↓ ADH ) → ↓ colloidal pressure →↑ filtration if water ↓ (when ↑ ADH) ↑ → colloidal pressure →↓ filtration Renal vasodilatation Vasodilatation (bradykinin , prostaglandin) →↑ renal blood flow ↑ → filtration Vasoconstriction of efferent (angiotensin II) → ↑ filtration ACE inhibitors are contraindicated in patients with renal artery stenosis. anti-inflammatory agents, such as aspirin that inhibit prostaglandin synthesis may cause significant reductions in GFR.

30. Pressures on nephron

31. Factors affecting GFR Protein intake ↑ protein → ↑ reabsorption AA in PCT ↑→ reabsorption of Na in PCT ( ↓Na in macula densa in DCT → ↑ renal blood flow ↑→ intraglomerular pressure  → glomerular hyperfiltration. This can cause damage to glomerular structure leading to or aggravating CKD. So, Meat and other protein sources are harmful in CKD patients. Glucose intake ↑ glucose ↑ → reabsorption glucose in PCT ↑ → reabsorption of Na in PCT ( ↓Na in macula densa in DCT → ↑ renal blood flow ↑→ intraglomerular pressure  → glomerular hyperfiltration. Such as diabetic mellitus

32. Nephron Autoregulation of GFR (homeostasis) How does GFR remain relatively constant despite changing mean arterial pressure? Myogenic response During high blood pressure Tubuloglomerular feedback at the Juxtaglomerular Apparatus During low or high blood pressure autonomic nervous system During low blood pressure Hormones During low blood pressure

33. Nephron Autoregulation of GFR Myogenic response Muscles of arteries are intrinsic myogenic in nature ↑ blood pressure → ↑ stretch of arteriolar smooth muscle → ↑ movement of Ca+ from the extracellular fluid into the cells → vasoconstriction → ↓ arteriole diameter → ↓ GFR

34. Nephron Autoregulation of GFR Tubulooglomerular feedback at the Juxtaglomerular Apparatus (JGA) By Macula densa The cells of the macula densa (as a chemo receptor ) monitor NaCl concentration in the fluid moving into the distal convoluted tubule. If GFR ↑ : ↑ blood pressure → ↑ renal blood flow→ ↑ filtration → ↑ NaCl movement and concentration Macula densa cells send a paracrine message ( adenosine ) causing the afferent arteriole to contract → ↓ GFR and NaCl movement. If GFR ↓ : ↓ blood pressure → ↓ renal blood flow→ ↓ filtration → ↓ NaCl movement and concentration ↑ Renin Release : Macula densa cells send a message (angiotensin II) causing the efferent arteriole to contract → ↑ GFR and ↑ NaCl Dilate the afferent arterioles → ↑ glomerular hydrostatic pressure → ↑ GFR

35. Mechanism (tubule glomerular feed back )

36. Juxtaglomerular Apparatus

37. Nephron Regulation of GFR Autonomic nervous system Changing arteriole resistance Sympathetic innervations to both afferent and efferent arterioles Norepinephrine, Epinephrine Constrict both afferent and efferent Acts on alpha receptors → vasoconstriction Used when ↓ blood pressure (severe hemorrhage) → Norepinephrine, Epinephrine Constrict both afferent and efferent arterioles → ↓GFR and conserve fluid volume . Hormones that constrict afferent and efferent arterioles, causing reductions in GFR and renal blood flow.

38. Nephron Regulation of GFR Hormones Changing the filtration coefficient Release of renin Angiotensin II is a strong vasoconstrictor Act mainly on efferent ↓ blood pressure → ↑ renin → vasoconstriction of efferent → ↑ GFR . Prost a glandins Vasodilators Act on a fferent ↓ blood pressure → ↑ prostaglandin→ ↑ renal blood flow → ↑ GFR

39. Major Hormones That Influence GFR and RFB.

40. Nephron Regulation of GFR Renin-Angiotensin-Aldosterone System (or low NaCl flow in JGA)

41. Measurement of GFR GRF is measured by : Inulin clearance test - more accurate   . Creatinine clearance test . Radioisotopes - not used

42. Measurement of GFR Inulin Inulin has two features: Inulin is a sugar and unfamiliar to kidney, so no enzymes can affect it. Amount filtrate = amount excreted in urine No secretion ,, no absorption Molecular weight is small (size 4nm) concentration in filtrate = concentration in plasm. Disadvantage It is exogenous Inulin needs to be infused into blood before test, so it is not suitable for clinical use Inulin can exhaust kidneys in renal compromised patients

43. Measurement of GFR Creatinine GRF is measured by a substance called creatinine . Creatinine has a feature: It is endogenous From muscles as creatinine phosphate slightly secreted Amount filtrate ≠ amount excreted in urine

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