Study guide: Renal Physiology and Filtration

📋 Course Outline

1. Kidney and Nephron Structure
2. Glomerular Filtration
3. Measuring Glomerular Filtration
4. Renal Plasma Flow
5. Blood Pressure Regulation
6. Tubular Functions and Clearance
7. Tubular Secretion and Acid Excretion
8. Tubular Reabsorption Principles
9. Glucose Reabsorption and Glycosuria
10. Passive Reabsorption and Renal Failure

📖 1. Kidney and Nephron Structure

🔑 Key Concepts & Definitions

• Nephron: The functional unit of the kidney, comprising the renal corpuscle, proximal convoluted tubule, loop of Henle, and distal convoluted tubule.

★ Must-know

• Each kidney contains about 1 million nephrons, which produce the primary and final urine.

📌 Cortical nephrons have short loops of Henle that penetrate little or not at all into the medulla, whereas juxtamedullary nephrons have long loops that extend deeply into the medulla.

Further detail

• Each kidney weighs about 150 g, receives part of the combined renal blood flow of about 1 L/min, and together the kidneys receive about one fifth of cardiac output.

• About 85% of nephrons are cortical and 15% are juxtamedullary; juxtamedullary nephrons contribute more to concentrating urine and conserving water.

• 🔄 Urine flows through these structures in order:
  1. distal convoluted tubule
  2. collecting duct
  3. minor calyces
  4. major calyces
  5. renal pelvis
  6. ureter
  7. bladder
  8. urethra

💡 Memory Hook

Urine travels from nephron to collecting duct, calyces, renal pelvis, ureter, bladder, and urethra.

📖 2. Glomerular Filtration

★ Must-know

• The glomerular filtration barrier consists of fenestrated capillary endothelial cells, a single basement membrane, and podocytes whose pedicels form filtration slits.

• Glomerular filtration is passive and depends on the filtration membrane's permeability and a pressure gradient.

• Blood cells are not filtered, filtration is reduced for molecules larger than 5 kDa, and filtration stops for proteins above 69 kDa, such as albumin.

📐 Formula - The effective filtration pressure is $\mathrm{PEF}=\mathrm{PS}-(\mathrm{PO}+\mathrm{PH})$, where blood pressure promotes filtration and oncotic and hydrostatic pressures oppose it.

Further detail

• Plasma solutes with negative charge cross the negatively charged glomerular basement membrane less readily.

📌 Water, urea, and glucose are fully filtered, whereas inulin is partly retained and proteins and protein-associated lipids are absent from primary urine.

💡 Memory Hook

Blood cells and large proteins stay in the blood; water and small solutes enter the filtrate.

📖 3. Measuring Glomerular Filtration

★ Must-know

• The glomerular filtration rate (GFR) is used to assess kidney function, but it may remain normal until 50% of glomeruli are affected.

📌 Persistent GFR below 60 mL/min indicates chronic kidney disease, whereas a rapid GFR decline is acute kidney injury.

📐 Formula - For a substance that is freely filtered and neither reabsorbed nor secreted, $\mathrm{GFR}=\frac{U\times V}{P}$, where U and P are urinary and plasma concentrations and V is urine flow.

Further detail

• Inulin clearance can measure GFR but requires infusion to maintain a stable plasma concentration and is costly; creatinine is used more often in routine practice.

• The example inulin measurements of plasma concentration 1 mg/mL, urine concentration 125 mg/mL, and urine flow 1 mL/min yield a GFR of 125 mL/min.

📐 Formula - The Cockcroft estimate is $\mathrm{GFR}=K\times\mathrm{weight}\times(140-\mathrm{age})/P_{\mathrm{creatinine}}$, with K equal to 1.23 for men and 1.04 for women.

📖 4. Renal Plasma Flow

★ Must-know

• The kidneys receive a plasma flow of about 600 mL/min when hematocrit is normal, and about 20% of renal plasma flow is filtered at the glomeruli.

• The para-aminohippuric acid (PAH) clearance estimates renal plasma flow because PAH is filtered and almost completely extracted from plasma by tubular secretion.

Further detail

• A GFR of 125 mL/min corresponds to about 180 L/day of filtrate, while final urine output is about 1.5 L/day.

• The renal plasma flow is about 900 L/day, so the 180 L/day filtered is approximately one fifth of that flow.

📐 Formula - Because PAH extraction is about 90%, renal plasma flow is estimated as $\mathrm{RPF}=C_{\mathrm{PAH}}/0.9$.

📖 5. Blood Pressure Regulation

★ Must-know

• Renal intrinsic autoregulation maintains renal plasma flow and GFR through a myogenic mechanism and tubuloglomerular feedback, mainly by acting on the afferent arteriole.

• 🔄 The myogenic response to increased afferent pressure proceeds as follows:

  1. stretch-sensitive channels are activated
  2. calcium enters smooth muscle cells
  3. the afferent arteriole constricts
  4. renal blood flow and GFR decrease

• When distal tubular NaCl decreases, macula densa cells release vasodilators such as nitric oxide and prostaglandin E2; when NaCl increases, they release vasoconstrictors such as endothelin and adenosine.

Further detail

• Intrinsic autoregulation is effective over mean arterial pressures of 80–180 mmHg and becomes ineffective below 80 mmHg.

• Below 80 mmHg, sympathetic catecholamines cause strong afferent vasoconstriction, lowering GFR to help raise arterial pressure and redistribute blood to vital organs.

📌 Below an arterial pressure of 45 mmHg, effective filtration pressure and GFR are zero.

💡 Memory Hook

Intrinsic autoregulation works across 80–180 mmHg; extrinsic regulation takes over below 80 mmHg.

📖 6. Tubular Functions and Clearance

🔑 Key Concepts & Definitions

• Tubular reabsorption: The movement of a substance from primary urine into blood in the peritubular capillaries.
• Tubular excretion: The movement of a substance from blood into urine, in addition to glomerular filtration.
• Clearance: The volume of plasma completely cleared of a substance per unit time.

📝 Essential Points

📐 Formula - For a substance, clearance is $C=\frac{U\times V}{P}$, where U is its urine concentration, V is urine flow, and P is its plasma concentration.

📌 A substance that is filtered and reabsorbed has clearance below GFR, whereas a substance that is filtered and secreted has clearance above GFR.

💡 Memory Hook

Reabsorption moves substances from tubular urine to blood; excretion moves substances from blood to urine.

📖 7. Tubular Secretion and Acid Excretion

★ Must-know

📌 Tubular secretion is synthesis of substances in the tubular wall, whereas tubular excretion transfers substances from blood into tubular urine.

• Urine pH cannot fall below 4.5, so free proton excretion is limited and protons are buffered by ammonia as ammonium.

Further detail

• Renal acid handling includes proton excretion in the proximal convoluted tubule and bicarbonate reabsorption after bicarbonate filtration at the glomerulus.

• Tubular cells convert glutamine to glutamic acid and ammonia through glutaminase; ammonia binds secreted protons in the collecting duct to form ammonium, which is excreted in urine.

💡 Memory Hook

Glutamine gives rise to ammonia, which binds secreted protons to form urinary ammonium.

📖 8. Tubular Reabsorption Principles

★ Must-know

• Active reabsorption uses specific energy-dependent transporters, secondary active reabsorption depends on active gradients, and passive reabsorption follows water movement.

• Substances reabsorbed in the proximal convoluted tubule include:

  • sodium
  • chloride
  • glucose
  • phosphate
  • bicarbonate

Further detail

• The sodium gradient created by Na/K-ATPase provides a driving force for reabsorption of other electrolytes and substances such as amino acids and glucose.

• Most renal oxygen consumption is devoted to sodium reabsorption, and proximal tubular solute reabsorption results in obligatory water reabsorption.

💡 Memory Hook

Active reabsorption uses transport and is saturable; passive reabsorption follows water movement.

📖 9. Glucose Reabsorption and Glycosuria

★ Must-know

• At normal blood glucose, about 1 g/L, all filtered glucose is reabsorbed and urinary glucose clearance is zero.

📌 When blood glucose reaches about 2 g/L, glucose begins to appear in urine because tubular reabsorption no longer captures all filtered glucose.

📌 At about 3.5 g/L blood glucose, glucose reabsorption reaches its transport maximum and further filtered glucose is excreted in urine.

Further detail

• Glucose reabsorption uses the sodium gradient created by Na/K-ATPase, cotransport through SGLT-2 into tubular cells, and exit to blood through GLUT2.

📌 Renal diabetes causes glycosuria despite normal blood glucose because glucose transporters are fewer, less expressed, or less effective; it is distinct from type I and type II diabetes.

💡 Memory Hook

Filtered glucose is reabsorbed until transport saturates; the excess appears in urine.

📖 10. Passive Reabsorption and Renal Failure

★ Must-know

• About 179 L of the 180 L of filtrate is reabsorbed as water, concentrating urea in the tubules and promoting its passive reabsorption, mainly in the proximal convoluted tubule.

📌 In renal failure, urine output and urea clearance are low while blood urea concentration is high, making elevated uremia a marker of renal failure.

Further detail

• About 60% of filtered calcium is passively reabsorbed in the proximal convoluted tubule, following sodium and water.

📌 Active reabsorption can be complete but is limited by transporter number, whereas passive reabsorption is incomplete and depends on water movement.

💡 Memory Hook

Reduced water reabsorption lowers urea clearance, while blood urea concentration rises in renal failure.