Renal Physiology Notes

Renal Physiology

Learning Objectives

• Overview of Renal Function
• Describe the major features of the nephron (Functional unit of the kidney)
• Describe renal blood flow and glomerular filtration
• Explain and discuss the mechanisms of fluid and solute reabsorption in the proximal convoluted tubule, loop of Henle and distal nephron
• Describe acid-base homeostasis

Overview of Renal Function

• Maintains body Fluids
• Maintains electrolyte balances
• Eliminates waste (filter)
• Regulates acid-base conditions

Kidney Structure

• Renal cortex
• Renal medulla
• Major calyx (2 or 3 of these)
• Renal pelvis
• Minor calyx
• Ureter
• Renal column (projects from cortex)
• Fibrous capsule
• Renal pyramid of the medulla
• To a calyx
• Bowman capsule
• Glomerulus
• Proximal convoluted tubule
• Distal convoluted tubule
• Juxtamedullary nephrons have loops of Henle that extend deep into the medulla.
• Cortical nephrons have loops of Henle that do not extend deep into the medulla.
• Papillary duct
• Thin segment descending limb
• Thick segment ascending limb
• Thin segment ascending limb
• Collecting ducts

Renal Blood Flow

• The Renal arteries → Segmental Artery → Interlobular Artery → Arcuate Arteries → Afferent Arteriole → Glomerulus → Efferent Arteriole → Peritubular Capillaries → Arcuate Vein → Interlobar Vein → Renal Vein
• Each set of glomerular capillaries and peritubular capillaries are associated with the same nephron
• Arcuate = arch shaped

The Nephron

1. Glomerulus – Filtration
2. Proximal Tubule – Absorption/Secretion of solutes
3. Loop of Henle – Concentration
4. Distal Tubule – Absorption/Secretion of solutes
5. Collection Ducts – Absorption/Secretion of solutes

Renal Corpuscle

• Diameter - Afferent arteriole > Efferent arteriole = Considerable Pressure
• This is the filtration pressure (Net 10 mmHg) forcing plasma through endothelium of the capillaries into capsular space (filtration fraction 20 %)
• Filtration occurs though fenestrations in glomerular capillaries, basement membrane and filtration slits in podocytes
• Slits can become inflamed & enlarged, enabling ↑ solutes (mainly proteins) to enter the urine - proteinuria is thus a sign of glomerular inflammation

Glomerular Filtration Rate

• In adults, the normal eGFR number is usually more than 90 ml/min.
• eGFR declines with age, even in people without kidney disease
• Estimated Glomerular Filtration Rate (eGFR) is a calculation used to estimate how well the kidneys are filtering certain agents.
• WARNING: Possible inaccurate estimates of GFR, especially in early stages of kidney disease
• Based on Age, Sex, Race and Serum Creatinine

Chronic Kidney Disease

• In adults, the normal eGFR number is usually more than 90 ml/min
• Quantify extent of chronic kidney disease (CKD) using eGFR

Plasma Filtration

• Fluid: Bowman’s capsule → proximal tubule
  1. Here filtered fluid/solutes can be reabsorbed into the peritubular capillaries.
  2. Fluid/solutes can also be transported out of the capillaries and secreted into the tubular fluid.
  3. The amount of a compound (eg glucose) excreted is the amount filtered plus the amount secreted minus the amount reabsorbed

Proximal Tubule

• The proximal convoluted tubule (PCT) is a segment of the renal tubule responsible for the reabsorption and secretion of various solutes and water.
• The main function of the PCT is to reabsorb water and solutes like sodium, which is continuously pumped into the interstitium to create a gradient that allows many other solutes and even water to be reabsorbed by tubule cells.
• Almost all of the glucose, lactate, and amino acids, and most of the phosphate and citrate that’s filtered by the glomerulus is reabsorbed with the help of sodium in the proximal convoluted tubule.
• Some solutes like Urea and water can simply diffuse across the cell down its concentration gradient into the interstitium and then into the capillaries.
• About 50% of the filtrated urea is reabsorbed this way.
• Tubule cell: layer not in contact with filtered fluid: contain sodium/potassium pumps which extrude sodium into the interstitial fluid.
• Sodium channels exist in the luminal (inner) membrane of the cells and so sodium passes out of the lumen into the cells down its concentration gradient.
• This sodium influx carries glucose with it.
• Water is reabsorbed down an osmotic gradient from the lumen into the cells and then out into the interstitial fluid
• Water reabsorption ≈ 70% of glomerular filtration

Proximal tubule - Transport

• Paracellular
• Transcellular
• Antiport or countertransport
• Symport exchange or cotransport
• Primary energy currency = organic metabolic substrates
• Metabolic substrates catabolized to produce ATP

Loop of Henle

• Defence of the extracellular fluid volume
• Urinary concentrating mechanism
• calcium and magnesium homeostasis
• bicarbonate and ammonium homeostasis
• urinary protein composition
• Fluid flows from the proximal tubule down into the thin descending loop of Henle, and up into the thick part of the ascending limb.
• The initial (thin) part of the loop has many special channels (called aquaporins) and this allows water to leave the tubule.
• As the fluid descends in the tubule it becomes more and more concentrated, because it is in equilibrium with the high concentration in the extracellular fluid in the renal medulla.
• Fluid flows around the end of the loop and up into the thick part of the ascending limb.
• THE THICK PART IS IMPERMEABLE TO WATER.
• HERE MEMBRANE PUMPS MOVE SODIUM AND CHLORIDE IONS OUT INTO THE EXTRACELLULAR SPACE BY ACTIVE TRANSPORT.
• This extrusion of sodium and chloride ions maintains the high extracellular fluid concentration in the renal medulla.
• Oxygen is supplied by the capillaries of the vasa recta.
• When it leaves the loop of Henle the fluid enters the distal tubule.
• The fluid entering the distal tubule is actually more dilute than plasma (about 100 mOsm/L) due to the extrusion of sodium and chloride.

Thin Descending Loop

• AQUAPORIN PROTEINS
• ONLY ALLOW WATER to PASS THROUGH

Thin Ascending Loop

• Na CHANNELS
• CI CHANNELS
• DOWN CONCENTRATION GRADIENT

Thick Ascending Loop

• Na-K-2Cl COTRANSPORTER
• DOWN CONCENTRATION GRADIENT

Countercurrent Multiplication

• COUNTERCURRENT MULTIPLICATION
• the PROCESS of CREATING the CONCENTRATION GRADIENT
• USES ATP

Countercurrent Multiplier Mechanism

• This process of pumping out salt into the extracellular fluid around the loop of Henle is called the countercurrent multiplier mechanism of urine concentration.
• The vasa recta provide a countercurrent exchange mechanism to preserve the concentration gradient despite a blood flow through the vasa recta capillaries.
• Filtrate entering the descending limb becomes progressively more concentrated as it loses water.
• Blood in the vasa recta removes water leaving the loop of Henle.
• The ascending limb pumps out Na^+, K^+, and Cl^-, and filtrate becomes hyposmotic.

Loop of Henle Summary

• As water and solutes are reabsorbed, the loop first concentrates the filtrate, then dilutes it.
  1. Filtrate entering the nephron loop is isosmotic to both blood plasma and cortical interstitial fluid.
  2. Water moves out of the filtrate in the descending limb down its osmotic gradient. This concentrates the filtrate.
  3. Filtrate reaches its highest concentration at the bend of the loop.
  4. Na^+ and Cl^- are pumped out of the filtrate. This increases the interstitial fluid osmolality.
  5. Filtrate is at its most dilute as it leaves the nephron loop. At 100 mOsm, it is hypo-osmotic to the interstitial fluid.
• Osmotic concentration = Measure of solute concentration, defined as number of osmoles of solute per litre

Loop Diuretics

• LOOP DIURETICS
• HELP the BODY LOSE WATER
• INHIBITS Na^+ REABSORPTION (H_2O follows Na^+ )

Distal Tubule

• Sodium, Potassium & divalent cation homeostasis

Distal Tubule

• Water reabsorption
• Solute reabsorption
• Variable solute reabsorption or secretion
• Sodium ions Na^+ are reabsorbed in exchange for potassium ions; these ion pumps are stimulated by aldosterone (A).
• When the pH of body fluids decreases, hydrogen ions are secreted in exchange for sodium ions.
• The DCT also contains carrier proteins that secrete toxins or drugs that did not enter the filtrate at the glomerulus.

Collecting Duct

• The collecting ducts, in particular, the outer medullary and cortical collecting ducts, are largely impermeable to water without the presence of antidiuretic hormone (ADH, or vasopressin)
• When ADH is present, aquaporins allow for the reabsorption of this water, thereby inhibiting diuresis

Body fluid homeostasis

• Receptors in hypothalamus sense increased salt concentration and signal posterior pituitary.
• Posterior pituitary increases ADH secretion.
• Blood reabsorbs more water from kidney; urine is more concentrated.
• Kidneys eliminate more water in urine.
• Posterior pituitary decreases ADH secretion.
• Hormones, such as antidiuretic hormone (ADH), regulate kidney function. High ADH levels signal the kidneys to decrease water lost in urine.

Renin-Angiotensin-Aldosterone System (RAAS)

• BP regulation
• The kidneys sense a decrease in blood pressure and release renin from the juxtaglomerular apparatus (JGA)
• Renin converts angiotensinogen to angiotensin I
• In the lungs, angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II
• Angiotensin II causes vasoconstriction, resulting in increased blood pressure
• Angiotensin II also stimulates the adrenal glands to release aldosterone
• Aldosterone promotes the reabsorption of sodium and water
• The circulating blood volume increases, further raising the blood pressure

Fluid & Electrolyte balance

• Secretion of ions, acids, drugs, toxins
• Reabsorption of water, ions, and all organic nutrients
• Production of filtrate
• Variable reabsorption of water sodium ions, and calcium ions (under hormonal control)
• Variable reabsorption of water and reabsorption or secretion of sodium, potassium, hydrogen, and bicarbonate ions
• Further reabsorption of water (descending limb) and both sodium and chloride ions (ascending limb)
• Delivery of urine to minor calyx

Acid Base Homeostasis

• Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function.

Acid Base

• Acid = A proton (hydrogen ion) donor
• Base = A proton (hydrogen ion) acceptor
• Bronsted-Lowry Theory
• A = Acid
• B = Base
• H = Hydrogen ion/Proton

Acid Base Balance

• In order to maintain acid base balance, the kidney must accomplish two tasks:
  1. Reabsorption of all filtered bicarbonate
  2. Excrete the daily acid load
• The kidney achieves these tasks effectively via the processes of:
  1. Bicarbonate reabsorption (involving sodium transport)
  2. Hydrogen secretion
  3. Excretion of hydrogen ions with urinary buffers titratable acids (e.g H^+ + HPO4^{2-} \rightarrow H2PO4^-) and ammonium (NH4 ^+).
• The ultimate acid-base regulatory organs
• Proximal convoluted tubule = Reclamation of 4500mEq of HCO_3^- each day 70-90%
• Reabsorption of ALL filtered bicarbonate
• Excrete the daily acid load (depending on the acid/base status) intercalated cells essentially have: reversed polarity
• Distal Renal control of Acid/Base Balance

Blood acid-base status (Interpretation)

• Normal blood pH range = 7.35-7.45
• Acidosis or alkalosis?
  • pH <7.35 Acidosis
  • pH >7.45 Alkalosis
• What is the type of acidosis?
• What is the type of alkalosis?
  • If the HCO_3^- low, the disorder is metabolic acidosis
  • If the CO_2 is high, the disorder is respiratory acidosis
  • If the PCO_2 low, the disorder is respiratory alkalosis
  • If the HCO_3^- is high, the disorder is metabolic alkalosis

Blood acid-base status

• Respiratory Acidosis
• Respiratory Alkalosis
• Metabolic Acidosis
• Metabolic Alkalosis

Metabolic Acidosis

• Not reabsorbing enough HCO_3^-
• Respiratory compensates by blowing off excess CO_2
• pH <7.35
• HCO_3^- <22
• Signs & Symptoms
  • Headache
  • Hyperkalemia
  • Muscle Twitching
  • Vasodilation
  • Low BP
  • Nausea / Vomiting / Diarrhea
  • LOC changes / Confused / Drowsy
  • Kussmal Respiration/Compensate
• Causes
  • Severe Diarrhea
  • Renal Failure / Issues
  • Shock
  • Diabetic Ketoacidosis

Metabolic Alkalosis

• Reabsorbing excess HCO_3^-
• Respiratory compensates by retaining CO_2
• pH >7.45
• HCO_3^- > 26
• Signs & Symptoms
  • Rapid/Shallow respirations
  • Tachycardic w/ possible dysrhythmias
  • Nausea / Vomiting/Diarrhea
  • Hypokalemia
  • Tingling in extremities
  • Muscle cramping
  • Decreased LOC / Confusion
• Causes
  • Excessive HCO_3^-
  • Loop Diuretics
  • Severe vomiting
  • Excessive GI Suctioning

Summary

• Structure of the functional unit of kidneys
• Renal blood flow and glomerular filtration
• Fluid and solute reabsorption in the proximal convoluted tubule, loop of Henle and distal nephron
• Proximal & Distal tubules of the kidneys are major sites for acid-base balance