How many nephrons are in each kidney?

About 1 million nephrons per kidney.

What are the two main types of nephrons?

Cortical nephrons and juxtamedullary nephrons.

What percentage of nephrons are cortical?

About 85%.

What percentage of nephrons are juxtamedullary?

About 15%.

Which nephron type is especially important for concentrating urine?

Juxtamedullary nephrons.

What are the three basic renal processes?

Filtration, reabsorption, and secretion.

Where are all renal corpuscles located?

In the renal cortex.

Which capillaries are associated with convoluted tubules?

Peritubular capillaries.

Which capillaries are associated with nephron loops?

Vasa recta.

What are the three types of renal capillaries?

Glomerular capillaries, peritubular capillaries, and vasa recta.

Define glomerular filtration.

Movement of protein-free fluid from glomerular capillaries into Bowman’s space.

What is net glomerular filtration pressure?

PGC - PBS - πGC.

Which pressure favors filtration in the glomerulus?

Glomerular capillary blood pressure (PGC).

Which two forces oppose glomerular filtration?

Fluid pressure in Bowman’s space (PBS) and plasma colloid osmotic pressure (πGC).

Is net glomerular filtration pressure normally positive or negative?

Positive.

What does GFR stand for?

Glomerular filtration rate.

Which substance is ideal for measuring GFR experimentally?

Inulin.

Why is inulin used to measure GFR?

It is freely filtered and is neither reabsorbed, secreted, nor metabolized.

Which endogenous substance is used clinically to estimate GFR?

Creatinine.

Why does creatinine slightly overestimate GFR?

Because it is filtered and undergoes slight secretion.

If clearance of a substance is greater than GFR, what has occurred?

Tubular secretion.

If clearance of a substance is less than GFR, what has occurred?

Tubular reabsorption.

Write the clearance formula.

C = (U x V) / P.

What does U represent in the clearance formula?

Urine concentration of the substance.

What does V represent in the clearance formula?

Urine flow rate.

What does P represent in the clearance formula?

Plasma concentration of the substance.

Which substances undergo filtration only?

Inulin and creatinine.

Which substances undergo filtration and partial reabsorption?

Electrolytes.

Which substances undergo filtration and complete reabsorption?

Glucose and amino acids.

Which substances undergo filtration and secretion?

Organic acids and bases such as PAH.

About how much water is filtered per day?

About 180 L/day.

About how much water is excreted per day on average?

About 1.8 L/day.

What percent of filtered water is reabsorbed?

About 99%.

About how much sodium is filtered per day?

About 630 g/day.

About how much sodium is excreted per day?

About 3.2 g/day.

What percent of filtered sodium is reabsorbed?

About 99.5%.

How much glucose is normally excreted in urine?

Zero under normal conditions.

What percent of filtered glucose is reabsorbed normally?

100%.

How much urea is filtered per day?

About 54 g/day.

How much urea is excreted per day?

About 30 g/day.

What percent of filtered urea is reabsorbed?

About 44%.

What are the two pathways for tubular reabsorption?

Paracellular diffusion and transepithelial mediated transport.

Which pathway accounts for most tubular reabsorption?

Transepithelial mediated transport.

How does Na+ cross the apical membrane during reabsorption?

By passive diffusion through membrane proteins down its electrochemical gradient.

How is Na+ moved across the basolateral membrane?

By the Na+/K+ ATPase.

In which nephron segment is Na+ reabsorption especially emphasized in the slides?

The proximal tubule.

Is sodium ever secreted into the renal tubules?

No.

What is the equation for sodium excretion?

Na+ excreted = Na+ filtered - Na+ reabsorbed.

How is glucose reabsorbed on the apical side of proximal tubule cells?

By SGLT, a sodium-glucose cotransporter.

How does glucose leave the proximal tubule cell basolaterally?

By facilitated diffusion through GLUT.

What drives glucose uptake through SGLT?

Na+ moving down its electrochemical gradient.

What is the renal threshold?

The plasma concentration at which transport saturation begins and the substance starts appearing in urine.

What is transport maximum (Tm)?

The maximum transport rate once carrier proteins are saturated.

Why does glucose appear in urine in diabetes mellitus?

Filtered load exceeds the tubule’s reabsorptive capacity.

What causes renal glucosuria?

A genetic mutation of the Na+/glucose cotransporter in the proximal tubule.

Is urea freely filterable at the glomerulus?

Yes.

Why is urea reabsorption in the proximal tubule linked to water reabsorption?

Water reabsorption concentrates urea in the lumen, allowing urea to diffuse down its gradient.

Which substances are commonly secreted by renal tubules?

H+, K+, choline, creatinine, and penicillin.

Tubular secretion is coupled to reabsorption of which ion?

Na+.

Which nephron segment reabsorbs most water and non-waste plasma solutes?

The proximal convoluted tubule.

Which segment is the major site of solute secretion except K+?

The proximal tubule.

Which segment creates the osmotic gradient and reabsorbs large amounts of ions but less water?

The loop of Henle.

Which segment is the major site of fine control of water and solute to produce urine?

The distal convoluted tubule and collecting duct.

Roughly what fraction of reabsorptive and secretory activity occurs in the proximal tubule?

About 80%.

What percentage of water reabsorption occurs in the proximal tubule?

About 67%.

What is the mechanism of water reabsorption in the proximal tubule?

Passive movement through AQP1.

What percentage of filtered water is reabsorbed in the loop of Henle?

About 15%.

Which part of the loop of Henle is permeable to water?

The thin descending limb.

Which part of the loop of Henle actively reabsorbs NaCl?

The thick ascending limb.

Is the ascending limb permeable to water?

No, it is impermeable to water.

How much water is reabsorbed in the distal tubule according to the water transport table?

None.

How much water is reabsorbed in the large distal tubule and collecting duct?

About 8 to 17% of filtered water.

Which hormone regulates water permeability in the collecting ducts?

ADH, also called vasopressin.

Which aquaporin is regulated by ADH on the luminal membrane?

AQP2.

Which aquaporins are found on the basolateral membrane of collecting duct cells?

AQP3 and AQP4.

Which aquaporin is abundant in the proximal tubule?

AQP1.

Where is ADH produced?

In hypothalamic neurons, especially the supraoptic nucleus.

From where is ADH released?

The posterior pituitary.

What stimulates ADH release?

Increased plasma osmolarity and reduced plasma volume.

Where does ADH act in the nephron?

Collecting duct cells.

How does ADH increase water permeability?

By activating adenylate cyclase, increasing cAMP/PKA signaling, and inserting AQP2 into the apical membrane.

What happens to collecting ducts in the absence of ADH?

They become almost impermeable to water.

What is water diuresis?

Excretion of excess water without excess solute.

What is osmotic diuresis?

High water excretion caused by excess solute in the urine.

What is diabetes insipidus?

A disorder causing large volumes of dilute urine due to ADH deficiency or renal unresponsiveness to ADH.

What causes central diabetes insipidus?

Failure to release ADH from the posterior pituitary.

What causes nephrogenic diabetes insipidus?

Kidneys do not respond properly to ADH.

Name conditions that increase ADH secretion.

Shock, pain, warm/hot weather, and water deprivation.

Name conditions that decrease ADH secretion.

Cold, humid environment, and alcohol.

What happens to ADH during water deprivation?

Plasma ADH increases, causing antidiuresis and water retention.

What happens to ADH after excess water intake?

Plasma ADH decreases, causing water diuresis.

What is countercurrent multiplication?

Multiplication of osmotic gradients along the loop of Henle due to opposite flow and different transport properties of its two limbs.

What is the key single effect produced by the ascending limb during countercurrent multiplication?

It creates a gradient by reabsorbing NaCl while remaining impermeable to water.

What approximate osmotic difference is created between interstitium and ascending limb fluid?

About 200 mOsm.

Why does fluid become concentrated in the descending limb?

Water leaves the descending limb because the medullary interstitium is hyperosmotic.

Why does tubular fluid become dilute in the ascending limb?

NaCl leaves but water cannot follow.

What is the approximate osmolarity of fluid entering the distal convoluted tubule in the slide?

About 100 mOsm/L.

How does ADH affect fluid in the collecting duct?

It allows water reabsorption so tubular fluid becomes more concentrated, approaching the osmolarity of the interstitium.

What is the function of the vasa recta in the medulla?

To preserve the medullary osmotic gradient by countercurrent exchange.

Does the vasa recta create medullary hyperosmolarity?

No, it helps prevent the gradient from being washed out.

Why is blood flow in the medulla low?

To minimize solute washout and preserve the osmotic gradient.

What substances can freely move in and out of vasa recta capillaries?

Ions, urea, and water.

What is the main role of urea recycling?

To help maintain high medullary osmolarity.

What percentage of filtered urea is reabsorbed in the proximal tubule?

About 50%.

What happens to about 50% of urea after that in the loop of Henle?

It is secreted back into the tubule.

How much of the original filtered urea is finally excreted according to the slide?

About 15%.

Why do kidneys need to produce concentrated urine?

To conserve water.

List the five mechanisms maintaining a hyperosmotic medulla.

Countercurrent anatomy, NaCl reabsorption in ascending limb, ascending limb impermeability to water, urea trapping, and vasa recta hairpin loops.

What is normal extracellular fluid pH?

About 7.35 to 7.45.

When is arterial plasma considered acidotic?

When pH is below 7.35.

When is arterial plasma considered alkalotic?

When pH is above 7.45.

What is the pH formula?

pH = -log[H+].

What does a high H+ concentration mean for pH?

Low pH, meaning acidic.

What does a low H+ concentration mean for pH?

High pH, meaning basic or alkaline.

Why are small pH changes important physiologically?

They alter protein shape, enzyme activity, neuronal activity, K+ balance, and cardiac rhythm.

What pH range is fatal according to the slide?

Below 6.8 or above 7.8.

Define an acid.

A substance that releases H+ in solution.

Define a base.

A substance that accepts H+ in solution.

What is the major extracellular buffer system?

CO2/HCO3-.

What are important intracellular buffers?

Phosphate ions and proteins, including hemoglobin.

What is a buffer?

A substance that binds H+ and reduces changes in pH.

What volatile acid is produced by the body?

CO2.

Name two nonvolatile acids mentioned in the slides.

Phosphoric acid and sulfuric acid.

Which sulfur-containing amino acids generate sulfuric acid?

Cysteine and methionine.

Which amino acids mentioned generate hydrochloric acid?

Lysine, arginine, and histidine.

How do lungs help regulate acid-base balance?

By adjusting ventilation to control CO2 and therefore H+ concentration.

How do kidneys help regulate acid-base balance?

By secreting H+, reabsorbing filtered bicarbonate, and generating new bicarbonate.

Which system provides short-term acid-base regulation?

The respiratory system.

Which system provides long-term acid-base regulation?

The kidneys.

How does increased H+ affect ventilation?

It stimulates ventilation.

How does decreased H+ affect ventilation?

It inhibits ventilation.

What is the key acid-base concept linking H+ loss and bicarbonate gain?

When 1 H+ is lost from the body, 1 HCO3- is gained by the body.

In alkalosis, what do kidneys excrete more of?

Bicarbonate.

In acidosis, what do kidney cells synthesize and add to blood?

New bicarbonate.

Is bicarbonate reabsorption dependent on H+ secretion?

Yes.

Where does most bicarbonate reabsorption occur?

Proximal tubule, ascending loop of Henle, and cortical collecting duct.

What happens when secreted H+ exceeds luminal bicarbonate?

Extra H+ binds filtered phosphate, and new bicarbonate is added to plasma.

What filtered buffer binds extra H+ in mechanism 1 of acidosis response?

HPO4^2-.

What is the net effect of phosphate buffering in tubular fluid during acidosis?

Net gain of bicarbonate in plasma.

Which nephron segment performs glutamine-based bicarbonate generation?

The proximal tubule.

What two products are formed from glutamine metabolism in proximal tubule cells?

NH4+ and HCO3-.

How is NH4+ handled after being formed in proximal tubule cells?

It is actively secreted into the lumen.

What happens to bicarbonate formed from glutamine metabolism?

It is added to plasma.

How do kidneys respond to acidosis overall?

They secrete more H+, reabsorb more bicarbonate, generate new bicarbonate, and excrete acidic urine.

How do kidneys respond to alkalosis overall?

They excrete bicarbonate, reduce glutamine metabolism and ammonium excretion, and produce alkaline urine.

What causes respiratory acidosis?

Decreased ventilation with increased blood PCO2.

Give an example cause of respiratory acidosis from the slides.

Emphysema.

How do kidneys compensate for respiratory acidosis?

By increasing H+ secretion and restoring acid-base balance.

What causes respiratory alkalosis?

Hyperventilation with decreased blood PCO2.

Give an example cause of respiratory alkalosis from the slides.

High altitude.

How do kidneys compensate for respiratory alkalosis?

By excreting more bicarbonate.

What are examples of metabolic acidosis from the slides?

Diarrhea, severe exercise, and diabetes mellitus.

How does the body compensate for metabolic acidosis?

By increasing ventilation and increasing H+ secretion.

What causes metabolic alkalosis according to the slides?

Prolonged vomiting.

How does the body compensate for metabolic alkalosis?

By decreasing ventilation and increasing bicarbonate excretion.

What links Na+ reabsorption to body fluid volume regulation?

Water reabsorption depends on Na+ reabsorption.

Why is plasma osmolarity closely linked to plasma sodium concentration?

Na+ is the main determinant of plasma osmolarity.

What hormone physiologically controls water reabsorption/excretion?

ADH.

What do baroreceptors detect for short-term sodium/volume regulation?

Changes in stretch caused by changes in blood pressure and blood volume.

Where are baroreceptors located?

Carotid sinus, aortic arch, major veins, and intrarenal sites such as JG cells.

How do reduced baroreceptor firing and increased renal sympathetic nerve activity affect GFR?

They constrict afferent arterioles and decrease GFR.

What is the short-term consequence of low plasma Na+ and low plasma volume via baroreceptors?

Decreased GFR and increased Na+ reabsorption.

What hormone provides long-term regulation of low Na+ levels?

Aldosterone.

What type of hormone is aldosterone?

A steroid hormone.

Where is aldosterone secreted from?

The adrenal cortex.

What triggers aldosterone release?

Low plasma volume associated with low sodium, mainly through the renin-angiotensin system.

Where does aldosterone act?

Late distal tubule and cortical collecting duct.

What does aldosterone do to sodium transport proteins?

It induces their synthesis.

What is the effect of aldosterone on sodium excretion?

It decreases sodium excretion.

How is Na+ reabsorption linked to K+ handling in the cortical collecting duct?

Na+ reabsorption is linked to K+ secretion.

What regulates aldosterone secretion when dietary sodium is high?

Aldosterone secretion decreases.

What regulates aldosterone secretion when sodium intake is low or Na+ is depleted?

Aldosterone secretion increases.

What substance acts on the adrenal cortex to stimulate aldosterone secretion?

Angiotensin II.

Where is renin secreted from?

Juxtaglomerular cells of the kidney.

What enzyme converts angiotensinogen to angiotensin I?

Renin.

What enzyme converts angiotensin I to angiotensin II?

ACE.

What three inputs regulate renin release from JG cells?

Sympathetic input, intrarenal baroreceptors, and signals from the macula densa.

What do juxtaglomerular cells sense?

Circulating plasma volume/stretch in the afferent arteriole.

What does the macula densa sense?

NaCl load in the distal tubular filtrate.

What happens to renin release when NaCl delivery to the macula densa falls?

Renin release increases.

What peptide opposes sodium retention and aldosterone action?

Atrial natriuretic peptide (ANP).

Where is ANP synthesized and secreted?

The cardiac atria.

What stimulates ANP secretion?

Increased Na+ concentration, increased blood volume, and atrial distension.

What does ANP do to aldosterone?

It inhibits aldosterone.

What does ANP do to GFR?

It increases GFR.

What does ANP do to sodium reabsorption?

It decreases sodium reabsorption.

What is the net effect of ANP on sodium excretion?

It increases sodium excretion.

Write the equation for potassium excretion.

K+ excreted = K+ filtered - K+ reabsorbed + K+ secreted.

Where is most filtered K+ reabsorbed?

Proximal tubule and loop of Henle.

Which nephron segment regulates urinary K+ concentration?

The cortical collecting duct.

What is hyperkalemia?

Excess K+ in the blood.

How does increased plasma K+ affect aldosterone secretion?

It stimulates aldosterone secretion.

How does decreased extracellular K+ affect aldosterone secretion?

Aldosterone production decreases.

What is the effect of aldosterone on K+ secretion?

It increases K+ secretion in the cortical collecting duct.