(26-28) Kidneys (AI Flahscards)

Define the Glomerular Filtration Rate GFR

The volume of fluid filtered from the glomeruli into Bowmans space per unit time

What does fenestrated capillary mean in the glomerulus

A capillary with many small pores that let water and small solutes pass into Bowmans capsule but block blood cells

What is the role of podocytes in the filtration barrier

They form a sieve like layer with foot processes that lets small molecules through but retains large proteins and cells

What size molecules are freely filtered at the glomerulus

Molecules smaller than roughly eight nanometres in diameter

What happens to protein bound drugs at the glomerulus

They are not filtered and stay in the blood because the protein drug complex cannot cross the barrier

Name the main functions of the kidney

Regulation of water salts and acid base balance removal of metabolic waste removal of foreign chemicals gluconeogenesis and hormone production

Which hormones are produced or activated by the kidney

Erythropoietin renin and activated vitamin D

What is the functional unit of the kidney

The nephron

Where do most nephrons sit in the kidney

At the interface between cortex and medulla

Into what structure do collecting ducts drain

The renal pelvis which then drains into the ureter

From where to where does glomerular filtration occur

From glomerular capillary blood into Bowmans capsule

What three basic processes determine how much of a substance is excreted

Filtration reabsorption and secretion

Define glomerular filtration rate

GFR is the volume of fluid filtered from glomeruli into Bowmans space per unit time

Which arteriole brings blood into the glomerulus

The afferent arteriole

Which arteriole carries blood away from the glomerulus

The efferent arteriole

How does constriction of the afferent arteriole affect GFR

It reduces glomerular pressure and decreases GFR

How does dilation of the afferent arteriole affect GFR

It increases glomerular pressure and increases GFR

How does constriction of the efferent arteriole affect GFR

It increases glomerular pressure and tends to increase GFR

How does dilation of the efferent arteriole affect GFR

It lowers glomerular pressure and decreases GFR

How many times per day is total body water filtered by the kidneys

About four and a half times per day

What happens to most of the water that is filtered by the kidneys

It is reabsorbed so only a small volume appears as urine

What does the presence of glucose in urine usually indicate

Very high blood glucose or damage to proximal tubular reabsorptive mechanisms

How is sodium reabsorbed at the apical membrane of proximal tubule cells

By cotransport with solutes such as glucose and by counter transport with hydrogen ions

What pump drives sodium reabsorption at the basolateral membrane

The sodium potassium ATPase pump

What happens to potassium moved into cells by the sodium potassium pump in tubular epithelium

It diffuses back to the interstitial fluid through potassium channels down its gradient

How is glucose reabsorbed in the proximal tubule

It enters via sodium coupled cotransport and leaves the cell through specific glucose transporters into blood

Which cotransporter mediates sodium uptake in the thick ascending limb

The sodium potassium chloride cotransporter NKCC

Why is the ascending loop of Henle important for concentrating urine

It pumps out sodium and chloride without water creating a hypertonic medullary interstitium

Why can water not leave the ascending loop of Henle

Because its epithelium lacks water channels and is effectively impermeable to water

What is the key permeability property of the descending loop of Henle

It is permeable to water but not to sodium

Why does water leave the descending limb of the loop of Henle

Because the surrounding interstitial fluid is hypertonic so water moves out by osmosis

What is meant by counter current blood flow around the loop of Henle

Blood in the vasa recta flows in the opposite direction to tubular fluid and helps preserve gradients

How does counter current blood flow support water reabsorption

Low salt blood takes up salt near the ascending limb then carries concentrated blood past the descending limb promoting water exit into blood

Where in the nephron are aquaporins especially important

In collecting duct cells

What is the effect of a high medullary interstitial sodium concentration on collecting duct water movement

It drives water out of the tubular fluid into the interstitium down the osmotic gradient

What hormone directly regulates water permeability in the collecting duct

Vasopressin also called antidiuretic hormone

On which cells does vasopressin act in the kidney

Collecting duct tubular cells

What is the mechanism of vasopressin action on collecting duct cells

It causes vesicles containing aquaporins to fuse with the apical membrane and increases water channels

Why does vasopressin act quickly compared with aldosterone

Because aquaporins are already synthesised and only need to be moved to the membrane

What happens to urine when vasopressin levels are high

Urine volume falls and osmolarity rises giving concentrated urine

What happens to urine when vasopressin levels are low

Urine volume rises and osmolarity falls giving dilute urine

What hormone regulates sodium reabsorption in the collecting duct

Aldosterone

What type of hormone is aldosterone

A steroid hormone

How does aldosterone increase sodium reabsorption

It increases synthesis of sodium channels and sodium potassium pumps in collecting duct cells

Why is the effect of aldosterone relatively slow

Because it depends on gene transcription and new protein synthesis

What overall effect does aldosterone have on blood pressure

It promotes sodium and water retention which tends to raise blood pressure

What does OAT stand for in renal physiology

Organic anion transporter

What does OCT stand for in renal physiology

Organic cation transporter

Where are OATs mainly located in the nephron

On proximal tubule cells

In which membrane are OAT1 and OAT3 mainly found

On the basolateral membrane facing blood

In which membrane is OAT4 mainly found

On the apical membrane facing tubular lumen

Which transporter reabsorbs uric acid in the proximal tubule

URAT1 on the apical membrane

Do OATs use passive or energy dependent transport

They mediate passive transport along concentration related gradients

Why are OATs important for drugs

They handle many anionic drugs and strongly influence renal secretion and clearance

What drug is a classical inhibitor of OATs

Probenecid

How did probenecid affect penicillin therapy historically

It reduced penicillin secretion into urine and prolonged levels in blood

How does probenecid help in gout

It inhibits uric acid reabsorption so more uric acid is lost in urine and plasma levels fall

Where are OCT2 and OCT3 located in the kidney

On the basolateral membrane of proximal tubule cells

Where is OCT1 mainly expressed

In liver with little expression in kidney

Which apical transporters work with OCTs in proximal tubule

MATE1 and MATE2 which exchange organic cations with hydrogen ions

Name two drugs that use OCT2 for renal excretion

Metformin and cimetidine

What is the interaction between metformin and cimetidine at OCT2

Cimetidine competes for OCT2 so metformin secretion falls and metformin levels rise

Which enzyme is central to renal control of bicarbonate and hydrogen ions

Carbonic anhydrase

What reaction does carbonic anhydrase catalyse

The reversible conversion of carbon dioxide and water to carbonic acid and then hydrogen ion plus bicarbonate

How does changing bicarbonate concentration alter pH

Changing bicarbonate shifts the equilibrium and alters hydrogen ion levels

Where is bicarbonate mainly reabsorbed in the nephron

In the proximal tubule

In bicarbonate reabsorption where do the secreted hydrogen ions go

They combine with filtered bicarbonate in the lumen to form carbonic acid

What happens to carbonic acid in the tubular lumen

It splits into carbon dioxide and water which diffuse into the tubular cell

What is the net effect of bicarbonate reabsorption on body bicarbonate stores

There is no net loss because newly formed bicarbonate replaces filtered bicarbonate

How does the kidney generate new bicarbonate via phosphate buffering

Secreted hydrogen ions bind filtered phosphate and are excreted while the paired bicarbonate remains in blood

How does glutamine metabolism generate bicarbonate

Glutamine is broken down to ammonia and bicarbonate ammonia is excreted and bicarbonate enters blood

During acidosis what happens to glutamine metabolism in the kidney

It increases to make more bicarbonate

During alkalosis what happens to glutamine metabolism in the kidney

It decreases so less new bicarbonate is produced

Define metabolic acidosis in simple terms

A state where hydrogen ion levels are raised and blood pH is low

How does the kidney correct metabolic acidosis

By increasing hydrogen ion secretion phosphate and ammonium excretion and bicarbonate generation

Define metabolic alkalosis in simple terms

A state where hydrogen ion levels are low and blood pH is high

How does the kidney correct metabolic alkalosis

By reducing hydrogen ion secretion and allowing excess bicarbonate to be excreted

How does urine pH affect weak acid drug excretion

Alkaline urine ionises weak acids and favours their excretion

How does urine pH affect weak base drug excretion

Acidic urine ionises weak bases and favours their excretion

Why are ionised drugs less likely to be reabsorbed from the tubule

Because charged molecules cross lipid membranes poorly so they stay in the lumen

How is sodium bicarbonate used in aspirin poisoning

It alkalinises urine so salicylic acid is more ionised and excreted faster

Which three processes together determine how much drug appears in urine

Glomerular filtration tubular reabsorption and tubular secretion

Why do highly protein bound drugs have low renal clearance

Because only unbound drug is filtered at the glomerulus

How does renal disease alter dosing of renally excreted drugs

Doses often need to be reduced or given less often to avoid accumulation

Why is understanding renal handling of drugs important in pharmacy

Because changes in kidney function alter drug clearance and toxicity ris