USMLE: Nephrology

CREST stands for?

Calcinosis

Raynauds

Esophageal dysmotiltiy

Sclerodactyly

Talangiectasias

What does the kidney start off as? (Renal embryology)

Pronephros

—disappears by week 4

Mesonephros

—fetal kidney during 1st trimester

—becomes part of male genital system

Metanephros

—becomes adult kidney

What renal embryology structure becomes adult kidney?

Metanephros

What embryologic structure gives rise to entire collecting system?

Ureteric buds

—induces Metanephros to differentiate into renal tubular structures

Without ureteric buds, you would get?

NO kidneys at all (bilateral renal agenesis)

—because stimulates Metanephros to become renal Tubular epithelium

What is Potter sequence?

Bilateral renal agenesis (kidneys do not form)

"POTTER" mneumonic

Pulmonary hypoplasia

Oligohydramnios

Twisted skin

Twisted face

Extremities

Renal agenesis

Horshoe kidney is?

When inferior parts of kidneys fuse to form one kidney, and as it ascends during development, will get hung up under inferior mesenteric a.

What artery traps Horshoe kidney?

Inferior mesentaric

What disorder is associated with Horeshoe kidney?

Turners

Blood flows into kidney through?

Renal a

Peripheral part of kidney?

Cortex (where glomeruli found)

What brings blood into glomeruli?

Afferent arteriole

Blood brain barrier layers?

Capillary endothelium

Basement membrane

Astrocyte foot processes

Glomerular filtration barrier layers? (Tufts of caps in glomeruli)

Capillary endothelium

—fenestrated

Basement membrane

—negatively charged to keep proteins from leaving caps

Podocyte foot processes

What is tufts of capillaries in glomeruli covered by?

Bowmans capsule

What is path of blood through glomeruli starting with afferent arteriole?

Afferent —> goes to glomerular capillaries (within Bowman's capsule) —> plasma, electrolytes, aa, glucose (protein CANT) ooze through caps and ends up in Bowmans space —> now called filtrate which goes to proximal convoluted tubule after this

What cant diffuse through glomerular capillaries?

Protein

RBC

Platelets

—exits through efferent arteriole

Where are juxtaglomerular cells located?

Afferent arteriole within the Juxtaglomerular apparatus (along with Macula densa)

What does the macula densa do?

Senses sodium in the distal convoluted tubule (which is touching afferent arteriole)

—if sodium gets too low, tells Juxtaglomerular cells to secrete renin

What stimulates JG to release renin?

Sympathetics (B adrenergic stim)

Low Sodium in Distal convoluting tubule (Macula densa)

Low pressure in afferent arteriole

What is the difference between cortical and juxtaglomerular nephrons?

Cortical

—start higher up in cortex, only a small portion of loop of henle dips into medulla

—NO vasa recta

Juxtagolmerular

—start LOW in cortex, and loop on henle penetrates deep into medulla

—also have vasa recta that wrap around loop of henle (supply nutrients to medulla and provide osmotic gradient)

Nephrons drain into?

Collecting tubules —> minor calyces —> (2 or 3 minors converge) major calyces —> Renal pelvis —> Ureters

What is the renal pyramid?

Within renal medulla composed of both nephrons and collect duct

—base toward cortex, apex (papilla) directed toward minor calyces (which it dumps into)

Where do the ureters join bladder? What is important to know of this location?

Ureterovesicular Junction (UVJ)

—common place for kidney stones to get stuck

Ureter pass under?

"Water (urine) under the bridge"

Women

—under uterine artery

Men

—under vas deferens

Intracellular fluid comprises?

28 L

Extracelluar fluid comprises?

14 L

10.5 — interstitial

3.5 — plasma

What percentage are people water?

60%

2/3 of such is Intracellular (40% of body weight)

1/3 extracellular

Where are the two places renal blood flow can go to?

Glomerulus

Renal tubules

If a substance has a clearance greater than GFR, what does this mean?

Some of substance in the blood is also being secreted by the tubules

Clearance?

"UV over P"

(Urine concentration of a particular substance) x (urine flow rate) / plasma concentration

measures in volume over time (mL/min)

Which substance is freely filtered by glomeruli, and its clearance as a result = that of GFR?

Inulin

—not secreted OR reabsorbed by renal tubules

GFR normal range?

90-120 ml/min (think 100)

If a substance has a clearance less than GFR, what does this mean?

Some of substance in blood is being reabsorbed by tubules

Creatinine is?

Product of the breakdown of creatine in muscles

—found in plasma naturally

freely filtered

—not reabsorbed

—only time amount is secreted by tubules

What is used to estimate GFR?

Creatine clearance

—because found naturally in blood and freely filtered, not reabsorbed, and only TINY amount secreted form tubules

Filtration fraction?

Portion of blood going to kidney that is filtered through glomerulus

FF = GFR/RPF

—normally 20%

How is renal plasma flow different than GFR?

Renal plasma flow takes in blood to glomeruli AND blood to tubules

What do we use to estimate renal plasma flow?

PAH

—all of PAH that makes it to kidney will end up in urine and be excreted

T/F All the blood that goes to kidneys is filtered by glomerulus.

F; some of it goes to renal tubules

What is NSAIDs effect on filtration fraction?

Constrict afferent arteriole

RBF down

GFR down

FF no net change

What is Angiotensin II effect on filtration fraction?

RBF down

GFR up

—bc back flow into caps and more blood is then going through glomeruli filtration barrier

FF goes up

Pathway of blood from renal aa to renal vein?

Renal artery —> afferent arterioles —> glomeruli capillaries (from here can squeeze through and become filtrate or continue on) —> efferent arterioles —> renal tubules (wrap around nephron) —> renal vein

What is ACE inhibitors effect on filtration fraction?

Dilate efferent arterioles

—so RBF goes up

FF goes down

If you have ureter stone obstruction or increase in serum protein, effect on filtration fraction?

GFR

—down

RBF

—stay same

FF

—DOWN

Reabsorbed equation?

Filtered - excreted

Hartnup disease?

Defiency in aa transporter for NEUTRAL aa's (tryptophan)

—unable to make niacin, and get pellagra as result

Excretion rate =

Urine concentration x urine flow rate

How are glucose and aa cleared?

Freely filtered in glomeruli SO HAVE to be reabsorbed by renal tubules

—Na glucose co transporter in Proximal Tubules that allows for glucose reuptake

—Na dependent transporters in PCT that allows for aa reuptake

Where does most reabsorption in nephron?

Proximal tubule

What is the limit to where nephron can reabsorb glucose in proximal convoluted tubule?

Plasma glucose over 160

—exceeds body's capacity to reabsorb and glucose is LOST in urine

For aa reabsorption in nephron, what allows this?

Na dependent transporters in PCTs

For:

—positve

—negative

—neutral

What does the proximal tubule do?

Glucose and aa reabsorbed

2/3 of fluid and electrolytes are reabsorbed

Fluid is reabsorbed isotonically

—electrolytes reabsorbed and water follows

How does glucose and amino acids specifically get reabsorbed into interstitial?

Sodium co transported —> which brings into tubule

Then Na/K pump uses ATP to drive either glucose or aa out into interstitium

What is primarily being reabsorbed in FIRST half proximal tubule?

Bicarb

Sodium

How is bicarb reabsorbed in FIRST half of proximal tubule?

Use of carbonic anhydrase within lumen AND within the proximal tubule cell

—H+ goes back into lumen

—Bicarb goes to interstitium

How is sodium and chloride being reabsorbed in proximal tubule?

By Na/K pump

What things are reabsorbed faster than water? (NOT ISOTONIC)

Phosphate

Amino acids

Glucose

—sodium and potassium are isotonic because water is reabsorbed with them at about same rate

Need to know this graph

PAH is so high up because it is being filtered and secreted, so increasing relative to plasma because water is being reabsorbed while it stays the same in tubular fluid (so tubular fluid high/plasma low)

Phosphate and AA/glucose are below because they are being reabsorbed faster than water into plasma, so concentration of them in tubular fluid is decreased as go on (why it is so low)

In 1st half of proximal tubule, sodium reabsorption associated with? What about 2nd half?

1st half

—bicarb

2nd half

—cloride

Thick ascending limb responsible for?

Na/2Cl/K symporter

—ACTIVELY reabsorbing sodium, potassium and chloride (was more passive in proximal tubule)

Impermeable to water

Calcium and Magnesium reabsorption

Pathway of Glomeruli to Collecting tubules?

Glomeruli —> PCT —> Loop of Henle (thin descending limb and then thick ascending limb) —> DCT —> Collecting tubules

Thin descending limb responsible for? How?

Water reabsorption

—impermeable to sodium

Interstitum is hypertonic so has water pass because of osmotic gradient

What Inhibits the Na/2Cl/K symporter in the thick ascending limb?

LOOP diuretics

Thin descending and Thick ascending limb effects on urine?

Thin descending

—concentrating bc only permeable to water (NOT sodium)

Thick ascending

—diluting bc NOT permeable to water but sucking up ions (sodium, chloride, potassium)

In early part of Distal tubule, what is going on?

Active reabsorption of sodium and cloride

NOT always impermeable to water

**Calcium reabsorption is under control of PTH**

What types of cells compose the collecting duct and the last segment of DCT? What do they do?

Principal cells (most of collecting tubule)

—reabsorb water and sodium

—secrete potassium

Intercalated cells (types Alpha and Beta)

—secrete either H+ (alpha) and bicarb (beta)

—reabsorb potassium

How does PTH cause increase in serum calcium?

Stimulates bone resorp

Stimulates kidneys to activate Vitamin D

Stimulates kidneys to reabsorb more Calcium (at early DCT)

What determines how much water is reabsorbed in distal tubules and collecting ducts?

ADH (vasopressin)

DCT/collecting duct function?

Concentrate urine

—can be greatly affected by ADH

How does ADH cause reabsorption of water in DCT/collecting ducts?

Binds to V2 of Principal cell

—tells cells to insert aquaporins into luminal surface of cells

—these aquaporins allow water to be reabsorbed

What kind of potassium sparing diuretics are aldosterone antagonists?

Spironolactone

Eplerenone

What class of diuretics directly affects principal cells?

Potassium sparing diuretics

What kind of potassium sparing diuretics inhibit epithelial Na channels?

Triamterene

Amiloride

What is the effect of aldosterone on principle cells and intercalated cells of collecting duct?

Principle cells

—increases Na reabsorption, and secretes potassium

Intercalated

—stimulates secretion of H+ ions

Site of secretion of organic anions and cations?

Proximal tubule

What diuretic works at the PCT?

Acetazolamide

Mannitol

Permeable to water ONLY in the presence of ADH?

Late DCT and Collecting Duct

What are ADRs of Acetazolamide?

Sulfa drug

Metabolic acidosis

—losing bicarb

Acetazolamide MOA? Used for?

carbonic anhydrase inhibitor

—increases removal of water but more over bicarb in urine

Altitude sickness

—get rid of bicarb

Alkalinize urine

Chronic glaucoma

What draws aqueous humor into eye?

Bicarb

Mannitol MOA

Osmotic diuretic causing osmotic load that stays in filtrate and prevents reabsorption of free water in PCT

What are your sulfa LOOP diuretics?

Furosemide

Bumetanide

Torsemide

Ethacrynic acid

—NOT sulfa, would use if pt has sulfa allergy

What two diuretics can work for glaucoma?

Mannitol

—acute angle closure glaucoma

Acetazolamide

—chronic glaucoma

Loop diuretics MOA?

Inhibit Na/2CL/K symporter in thick ascending loop of henle

Thiazides are used for?

FIRST LINE for essential HTN

—not really for CHF (would use loop for this)

Loop diuretics vs Thiazides?

Loops lose calcium

Thiazides do NOT, and more commonly for HTN over loop

When do we use Loop diuretics?

When you want to get rid of water quickly

—CHF

—pulmonary edema

—nephrotic syndrome

—cirrhosis

Loop diuretics ADR?

Ototoxicity

Nephrotoxic

Hypokalemia

What are examples of your thiazide drugs?

Hydrochlorothiazide

—most commonly used

Chlorothiazide

Chlorthalidone

Metolazone

Thiazide MOA

Inhibit Na+/Cl- cotransporter therefore inhibiting Na+ reabsorption in the DCT

—retain CALCIUM (good if pt has osteoporosis with HTN)

Thiazides ADR?

Low potassium

Low sodium

High glucose

High lipids

High calcium

SULFER drugs

Someone with chronic CHF needs what 3 meds?

B blocker

ACE inhibitor (or ARB)

Aldosterone antagonist

T/F Thiazides are not sulfa drugs.

F; they are, so would not use with sulfa allergy

What are your potassium sparing diuretics?

"Potassium please have a SEAT" (cause you want to retain potassium)

Spironolactone

Eplerenone

Amiloride

Triamterene

—bold are aldosterone antagonists

For diuretics as a whole, what are ADRs? Name the exceptions

Increased urinary sodium and chloride

—except Acetazolamide

Increased urinary potassium

—except potassium sparing diuretics

Acidosis

—carbonic anhydrase inhibitors cause this

Alkalosis

—loops and thiazides cause this

Potassium sparing diuretics ADR?

High potassium

Gynecomastia

What produces 1,25 Dihydroxycholecalciferol (active Vitamin D)?

Enzyme 1a hydroxylase which is induced by PTH in the kidney

What hormones are produced from the kidney?

Renin

Vitamin D (1,25 Dihydroxycholecalciferol)

—by PTH

Erythropoietin

Prostaglandins

ANP by the atria in response to stretched walls, does what to increase water and sodium excretion?

Constricts efferent arterioles and dilates the afferent arterioles