Lecture 11: Renal Physiology I-II

• The functions of the Kidneys include excretory, regulatory, endocrine-related, and metabolic functions.
• Excretory functions involve the removal of waste and foreign substances.
• Regulatory functions include regulating H₂O, electrolytes, osmolarity, blood pressure, and acid/base balance.
• Endocrine-related functions are related to renin and erythropoietin as well as the activation of vitamin D3.
• Metabolic functions involve gluconeogenesis.

Anatomy of the Kidneys

• The functional unit of the kidneys is the nephron, which can be either cortical or juxtamedullary
• The kidneys contain two capillary networks.
• There is communication between plasma and pre-urine in the kidneys.

Cortical and Juxtamedullary Nephrons

• Juxtamedullary nephrons have a long loop of Henle and vasa recta.
• Juxtamedullary nephrons contribute to the medullary vertical osmotic gradient (300-1200 mOsm/L).
• Juxtamedullary nephrons also contribute to urine concentration and dilution.

Urine Formation

• Urine formation involves filtration, reabsorption, secretion, and excretion.
• Urine excretion is calculated as Filtration - Reabsorption + Secretion.

Glomerular Filtration

• GFR (glomerular filtration rate) refers to the volume of plasma that is filtered by the glomeruli per unit of time; about 125ml/min
• Filtration fraction calculation is GFR/Renal Plasma Flow
• 20% of renal plasma flow is filtered.

Filtration Membrane (Barrier)

• The filtration membrane consists of endothelium fenestrations, a basement membrane meshwork with negative charge, and podocytes (epithelium) with slit pores.

Dynamic of Glomerular Filtration

• GFR = Kf x net filtration pressure, with Kf representing the filtration coefficient.
• Outward forces promote filtration, while inward forces oppose it.

Regulation of GFR and Renal Blood Flow (RBF)

• GFR and RBF remain constant when arterial blood pressure changes between 80 and 180 mmHg; autoregulation.

Tubuloglomerular Feedback

• Juxtaglomerular apparatus: afferent arteriole granular cells produce renin, mesangial cells and macula densa detecting salt concentration change in the tubular fluid.

Myogenic Tone

• Myogenic tone is intrinsic to vascular smooth muscle cells.
• It causes constriction in response to stretching caused by increased arterial blood pressure.

Tubular Reabsorption & Secretion.

• Filtration load = GFR x Plasma Concentration
• Urine excretion = Filtration and Renal Tubular Handling

Tubular Transport

• Types of tubular transport include trancellular vs. paracellular transport, active vs. passive transport, primary vs. secondary active transport, and co-transport vs. counter-transport.

Transport Maximum

• Normal adult transport maximum for glucose: ~375 mg/min
• Glucose filtration (filtration load/tubular load) can be found with GFR x Plasma Concentration
• Normally, all glucose filtered is reabsorbed (125 mg/min < 375 mg/min), so glucose excretion is 0.

Transport in the Proximal Tubule

• 67% Na+ actively reabsorbed with basolateral membranes as Na+/K+ ATPase and apical membrane as Na+ cotransporter and Na+/H+ counter-transporter
• 67% of filtered Na+ actively reabsorbed and slightly less than 67% filtered Cl passively reabsorbed.
• 67% of filtered H₂O is osmotically reabsorbed, while all filtered glucose and amino acids are reabsorbed through secondary active transport.
• 50% of filtered urea is passively reabsorbed.
• The end of the proximal tubule: Isosmotic

Passive Reabsorption of Cl, H₂O, and Urea

• Cl is reabsorbed down the electrical gradient through the leaky tight junctions between epithelial cells.
• H₂O is reabsorbed osmotically in the proximal tubule due to aquaporin (water channel) and leaky tight junctions.
• Urea is reabsorbed down its concentration gradient created by H₂O reabsorption.

Cell Model of HCO3 Reabsorption in the Proximal Tubule

• 80% Filtered HCO3 is reabsorbed in the proximal tubule.

Transport in the Loop of Henle

• Ascending limb: impermeable to H₂O but permeable to Nat and 25% of Na+ actively reabsorbed.
• Descending Limb: 20% of filtered H₂O osmotically reabsorbed and relatively impermeable to Nat.

Transport in the Early Distal Tubule

• Impermeable to H₂O.
• Permeable to Na+: 5% Na+ actively reabsorbed; basolateral membrane as Na+/K+ ATPase and an apical membrane with Na+/Cl cotransporter.
• Diluting segment, with thiazide diuretics.

Transport in the Late Distal Tubule and Collecting Duct -- I

• Principle cells actively reabsorb 3 % of filtrate through the basolateral membrane as Na+/K+ ATPase and the apical membrane as an epithelial Na+ channel.
• Na+ reabsorption and K+ secretion regulated by aldosterone.
• Permeability to H₂O is regulated by ADH (anti-diuretic hormone).
• Diuretics: Na+ channel blocker and aldosterone receptor antagonist.

Transport in the Late Distal Tubule and Collecting Duct -- II

• Type A intercalated cells perform H+ secretion via H+-ATPase and H+-K+-ATPase as well as K+ reabsorption.
• Type B intercalated cells performs HCO3 secretion and H⁺ reabsorption in alkalosis as well as K+ secretion

K+ Transport Along the Nephron

• Along the proximal tubule, early K+ is reabsorbed.
• Along the proximal tubule, Para-cellular diffusion of K+ through the tight junctions
• In principle cells of the Cortical Collecting Tubule (CCT) K+ is secreted via ENaC chanels
• In alpha INTERCALATED CELL of the CORTICAL COLLECTING TUBULE (CCT) secreted in the H+ channel

Calcium Transport Along the Nephron

• Reabsorbed though out the proximal tubule
• Reabsorbed in the thick ascending limb
• In the distal convoluted tubule, calcium is sent out the tubule though the ATP channel

Phosphate Transport Along the Nephron

• In the proximal tubule, it uses NaPi-lla

Hormonal Control of Tubular Reabsorption

• Aldosterone: Collecting tubule and duct; NaCl, H 2 O reabsorption, ↑ K+ secretion, ↑ H+ secretion
• Angiotensin II: Proximal tubule, thick ascending loop of Henle/distal tubule, collecting tubule; NaCl, H 2 O reabsorption, ↑ H+ secretion
• Antidiuretic hormone: Distal tubule/collecting tubule and duct; H 2 O reabsorption
• Atrial natriuretic peptide: Distal tubule/collecting tubule and duct; NaCl reabsorption
• Parathyroid hormone: Proximal tubule, thick ascending loop of Henle/distal tubule; PO 4 reabsorption, ↑ Ca ++ reabsorption

Effects of Aldosterone

• Na+ reabsorption and K+/H+ secretion in the late distal tubule and collecting duct.

Juxtaglomerular Apparatus

• Afferent arteriole granular cells (JG cells) produce renin, mesangial cells, and macula densa. Macula densa detects salt concentration change

Renin-Angiotensin-Aldosterone System (RAAS)

• Renin is released and is a part of angiotensinogen converting it to Angiotensin I
• Angiotensin-converting enzyme converts Angiotensin I to Angiotensin II
• Angiotensin II causes aldosterone release

Effects of Ang II

• Vasoconstriction via constriction of efferent arteriole > afferent arteriole constriction.
• Leads to renal retention of salt and water through tubular Na+ reabsorption increase. Proximal tubule, Thick ascending limb of loop of henle. Also in Distal tubule, Collecting tubule

Effects of ADH/AVP

• H₂O
• Late distal tubules, collecting tubules, and medullary collecting ducts epithelial cells, V₂ receptors on the basolateral membrane.
• Insertion of aquaporin 2 onto the apical membrane, increasing water reabsorption

Atrial Natriuretic Peptide (ANP)

• Inhibits NaCl and water reabsorption.
• Causes vasodilation.
• Inhibits RAAS and ADH/AVP secretion.

Renal Clearance (Plasma Clearance)

• Renal clearance of a substance refers to the volume of plasma that is completely cleared of the substance by the kidneys per unit time.

Substance (X) is Filtered but not Reabsorbed or Secreted

• If Its Plasma Clearance = GFR, substance X is filtered in GFR with 125 ml/min plasma.
• What is filtered will be cleared/excreted because of no reabsorption or secretion.
• Example: inulin
• Application: measurement of plasma clearance of inulin can be used to estimate GFR.

Substance (X) is Filtered and Reabsorbed but not Secreted

• If Its Plasma Clearance < GFR with Substance X, but some is reabsorbed
• Example: Glucose's, where plasma clearance = 0

Substance (X) is Filtered and Secreted but not Reabsorbed

• Substance X is filtered in GFR and secreted by the tubules

Application of Clearance

• A substance filtered but not reabsorbed or secreted like -Inulin and creatinine can be used to measure GFR A substance is filtered and secreted completely but not reabsorbed PAH (para-aminohippuric acid)
• Its clearance can be used to measure renal plasma flow

III. Urine Concentration and Dilution

Is associated with juxtamedullary nephrons

Urine Concentration

• "Vertical osmotic gradient" in the Medulla

Transport in the Loop of Henle

25% of filtered Na+ reabsorbed, iMPERMEABLE TO H20 ,Na+ (to establish a 200-mOsm/L concentration gradient ,between the tubular fluid and the interstitiafluid)

Countercurrent Multiplier

• Juxtamedullary Nephron (Long Loop of Henle) . To generate the vertical osmotic gradient,.kidney medulla

Countercurrent exchange

Happens Vasa Recta to preserve the vertical osmotic gradient in the kidney medulla

Micturition

The micturition reflex is an entirely spinal reflex. Is internal urethral sphincter: Is Autonomic involuntary control . The external urethral sphincter:Is tonic