NEPHRO: IE 1

How do the kidneys play a role in regulating pH? 

Kidneys control pH by secreting H+ into the urine and through the return of HCO back to the blood. 

Name the 2 hormones produced by the kidneys and their effect on the body. 

Calcitrol (active vitamin D) to increase calcium levels and erythropoetin to increase RBC

List waste products excreted by the kidneys 

Ammonia, urea, bilirubin, creatinine, uric acid, water, electrolytes, drugs & toxins

Anatomical location of kidney

Urinary Anatomy

• Describe organs in the urinary system in the order the urine passes through them

• Describe fluid flow in the nephron

Kidney → Ureters → Bladder → Urethra 

Afferent and efferent arterioles → Glomerulus → PCT → Descending Thin Limb of Henle’s → DCT → Collecting duct

Kidney Anatomy

Renal Capsule Cortex

90% of renal blood flow goes to the cortex, which is where all glomeruli are located.

Medulla

Only receives 10% of renal blood flow. 

Describe Renal Blood Flow

Renal arteries branch from the abdominal aorta

Renal arteries branch into segmental, interlobar, arcuate, and interlobular arteries.

Afferent arterioles carry the blood into the glomerulus. 

Efferent arterioles carry filtered blood through the peritubular capillaries (cortical nephrons) and back to the renal vein 

• Peritubular capillaries reclaim resorbed water and ions and secrete excess products for excretion.

Compare the 2 types of nephrons

• % of all nephrons

• Key structural feature/roles

1. Cortical nephrons

   1. 85%

   2. Handle the bulk of blood filtration and routine waste removal

2. Juxtamedullary nephrons

   1. 15%

   2. Possess much longer loops of Henle that extend deep into the renal medulla to concentrate urine and conserve water

Glomerular Histology:

Name the three cell types/layers that make up the glomerular filtration barrier. 

Porous endothelial cells

Podocytes

Basement membrane 

Glomerulus filter is [] and [] selective

Charge

Size

What is able to pass through the glomerulus freely and what is blocked? 

Pass through: Water, ions, glucose, amino acids

Blocked: Proteins and blood cells

 What creates the pressure gradient that drives filtration into Bowman's space? 

Hydrostatic pressure → Afferent is larger than the efferent, creating back pressure

Proximal Tubule reabsorbs 80-85%s [], 100% [], and most [] and [].

This reabsorption mechanism depends on a [weak/strong] Na+ gradient that has [low/high] Na+ inside the cell

HCO3, Filtered gluose, mineral salts and amino acids

Strong → Low

Which transporter on the apical/luminal membrane secretes H⁺ into the proximal tubule lumen? Which gradient allows it to do so?

Na⁺/H⁺ exchanger (NHE3)

Na⁺/K⁺ ATPase → This process depends on the Na+/K+ ATPase because it maintains a low intracellular Na⁺concentration by pumping Na⁺ out of the cell and K⁺ into the cell, which creates the Na+ gradient that drives NHE3 to bring Na⁺ into the cell in exchange for H⁺.

Once H⁺ is secreted by NHE3 into the proximal tubular lumen, what does it combine with? What does it form?

Filtered HCO₃⁻

Carbonic acid

What allows CO2 to diffuse freely into the tubular cell? What happens after that?

Carbonic anhydrase IV

After CO2 diffuses into the proximal tubule cell, Carbonic Ahydrase II allows for the ionization of H+ & HCO3

Which transporter moves HCO₃⁻ from the proximal tubule cell into the interstitium/blood?

Na+ /HCO3- cotransporter (NBC1)

Compare SGLT2 and SGLT1: 

Transporter	Location  (early/late)	Affinity  (high/low)	Capacity  (high/low)	Glucose  Reabsorption
SGLT2
SGLT1

Transporter	Location  (early/late)	Affinity  (high/low)	Capacity  (high/low)	Glucose  Reabsorption
SGLT2	Early	Low	High	90%
SGLT1	Late	High	Low	10%

Glucose moves against its concentration gradient by leveraging the [] gradient

Glucose gets transported into the interstitium by []

If plasma glucose exceeds [] mg/dL then SGLT capacity to transport glucose is exceeded, leading to glycosuria

Na+

GLUT2

180

Segment	Water Permeable? (y/n)	What is reabsorbed/  key transporter	Passive/Active Transport
Thin Descending Limb

Segment	Water Permeable? (y/n)	What is reabsorbed/  key transporter	Passive/Active Transport
Thin Descending Limb	Y → High water permeability	Water reabsorption occurs via aquaporin-1 channels and leaky tight junctions between cells	Passive

Loop of Henle Thin Descending Limb

As the tubule descends, it encounters an increasingly [] medulla

• When will water leave?

• What is the osmotic gradient generated by in the medulla?

Hyperosmotic medulla

Water leaves the lumen until osmotic equilibrium is reached

The osmotic gradient is generated by counter-current multiplication in the ascending limb

T/F: Tubular fluid becomes progressively more concentrated as it descends through the medulla

T

Segment	Water Permeable? (y/n)	What is reabsorbed/  key transporter	Passive/Active Reabsorption
Thin Ascending Limb

Segment	Water Permeable? (y/n)	What is reabsorbed/  key transporter	Passive/Active Reabsorption
Thin Ascending Limb	N → d/t absence of aquaporins channels	Na+ and Cl- from the tubular fluid into the medullary interstitium	Passive

T/F: Tubular fluid in the thin ascending limb becomes more concentrated as it ascends.

F → Since there are no aquaporin channels, water cannot follow the solute that is removed from the tubular lumen. Consequently, the tubular fluid becomes progressively more diluted as it ascends.

Segment	Water Permeable? (y/n)	What is reabsorbed/  key transporter
Thick Ascending Limb

Segment	Water Permeable? (y/n)	What is reabsorbed/  key transporter
Thick Ascending Limb	N	NKCC2 is the primary transporter in the luminal membrane and drives reabsorption of Na+, K+ and Cl-

What is the main role of the Na⁺/K⁺-ATPase in the distal tubule?

Maintains low intracellular Na+

Segment	What is reabsorbed/  key transporters involved
Distal Convoluted Tubule

Segment	What is reabsorbed/  key transporters involved
Distal Convoluted Tubule	Na+, Cl-, Ca2+, Mg2+ Na+-Cl (NCC) → trasport Na+ and Cl- Parathyroid hormone (PTH) receptor → helps reabsorbs Ca2+ Na+/Ca2+ & → transports Ca2+ to blood

The NCC transporter moves which substances from the tubular fluid into the distal tubule cell?

Na + Cl

What hormone promotes Ca²⁺ reabsorption in the distal tubule?

Parathyroid hormone

→ promotes Ca²⁺ reabsorption by driving expression of voltage-gated Ca2+ channel expression

After Ca²⁺ enters the distal tubule cell, which mechanisms transport Ca²⁺ toward the interstitium? Select all that apply.
A. Na⁺/Ca²⁺ exchanger
B. Ca²⁺-ATPase
C. Na⁺/K⁺-ATPase
D. NCC

A + B

x

x

What is the final site for for water reabsorption?

Collecting duct

T/F: High water permeability exists in the absence of antidiuretic hormone (ADH).

F → Low

Which receptor and intracellular signaling pathway does ADH activate to increase water permeability in the collecting duct?

Circulating ADH activates vasopressin V2 receptors that increase cAMP and cause aquaporins (AQP2) to insert into the apical membrane, increasing water permeability.  

 What hormone increases the expression of ENaC, ROMK and Na+/K+-ATPase in the collecting duct?

Aldosterone

What drives both Na⁺ reabsorption and K⁺ secretion in the collecting duct?

Passive NA/KATPase

Na+ → Through apical ENaC

K+ → Renal Outer Medullary K+ (ROMK) channels

Nephron Summary

 ↓ Blood pressure → [] cells detect the decrease → ↑ []  

↓ Tubular Na⁺ → [] cells detect the decrease → ↑ [] → stimulation of []  cells → ↑ renin 

NSAIDs → inhibition of COX-2 → ↓ [] → ↓ renin release 

 ↓ Blood pressure → juxtaglomerular cells detect the decrease → ↑ renin 

↓ Tubular Na⁺ → Macula densa cells detect the decrease → ↑ PGE2 → stimulation of juxtaglomerular  cells → ↑ renin 

NSAIDs → inhibition of COX-2 → ↓ PGE2 → ↓ renin release 

Blood pressure is monitored by [] in the juxtaglomerular apparatus

Stretch receptors

Amiloride: ENaC

Spironolactone: Mineralocorticoid/Aldosterone pathway

Furosemide: NKCC2

Diamox: Carbonic anhydrase

Hydrochlorothiazide: NCC

Which of the following is NOT one of the three jobs of the kidney?

A. Excretory — filtration, secretion, reabsorption

B. Endocrine — renin and erythropoietin

C. Manufacturing red blood cells directly in the renal cortex

D. Metabolic — activating vitamin D and metabolizing drugs

A. Excretory — filtration, secretion, reabsorption

B. Endocrine — renin and erythropoietin

C. Manufacturing red blood cells directly in the renal cortex

D. Metabolic — activating vitamin D and metabolizing drugs

As kidney function declines, Scr increases. The overestimate is about []% at all levels of GFR

10-40%

What is the Basic Metabolic Panel Fishbone?

What is the Elderly CrCl rule?

Age ≥ 65 and Scr < 0.8 → round Scr up to 0.8

What can raise Scr and lower Scr?

What are some medications that can block creatinine secretion? 

a. Cimetidine

b. Cobicistat

c. Trimethorprim

d. Dolutegravir 

E. Amiodarone

 Which medications need to be renally adjusted? 

a. Fentanyl 

b. Omeprazole 

c. Lithium 

d. Allopurinol 

e. Moxifloxacin 

f. Ceftriaxone 

g. Gentamicin 

h. Rivaroxaban 

i. Warfarin 

j. Vancomycin

 Which medications need to be renally adjusted? 

a. Fentanyl 

b. Omeprazole 

c. Lithium 

d. Allopurinol 

e. Moxifloxacin 

f. Ceftriaxone 

g. Gentamicin 

h. Rivaroxaban 

i. Warfarin 

j. Vancomycin

Which antibiotics, fluoroquinolones, antimicrobials, anticoagulants, opioids, diabetes medications, cardiac medications, and GI medications do NOT need to be renally adjusted?

Cetriafoxone, naficillin, dicloxaxillin

Moxifloxacin

Azithromycin, doxycycline, clindamycin, linezolid

Warfarin, unfractioned heparin

Fenatlyl, methadone

Linagliptin

Metoprolol, carvedilol

PPIs

Advantages of Cystatin C

Production is not affected by muscle mass, diet, or activity

Use the combined creatinine + cystatin C equation when Scr is unreliable

Goal Urine Output

>0.5 mL/kg/hr

Which one of these medications does NOT require renal dose adjustment?

A. Enoxaparin B. Metformin C. Ceftriaxone D. Apixaban

C

Which anticoagulant does NOT require renal dose adjustment?

A. Enoxaparin B. Apixaban C. Dabigatran D. Warfarin

D. Warfarin

Which opioid is safest in renal impairment (no renal adjustment needed)?

A. Morphine B. Hydromorphone C. Meperidine D. Fentanyl

D. Fentanyl

What weight should be used for the following obesity populations?

< 30 (normal / overweight)

30-39.9 (class I-II obesity)

≥ 40 (class III / morbid)

< 30 (normal / overweight) → TBW or IBW per the standard rules

30-39.9 (class I-II obesity) → Total body weight (TBW) generally OK

≥ 40 (class III / morbid) → Lean Body Weight (LBW)

Equations to use:

[] to stage; [] to dose; [] is retiring; [] for kid

CKD-EPI to stage; Cockcroft-Gault to dose; MDRD is retiring; Schwartz for kids

T/F: In AKI, use steady-state equations

F → they do not apply

Do the problems from post-class!

🙂

What fraction of total body water is contained in the intracellular fluid (ICF) versus extracellular fluid (ECF)? Which major ions primarily determine the osmolality of each compartment?

ICF: 60% of TBW

• Determined by K+ and its accompanything anions (mostly organic and inorganic phosphates)

ECF: 40% of TBW

• Na+ and its accompanyting anions (chloride and bicarbonate)

What is the most abundant cation in the body? 

Potassium

The sodium-potassium ATPase (Na+-K+-ATPase) pump maintains increased intracellular stores of potassium by transporting [] out and [] into the cell. 

3 Na+

2 K+

Compare which factors promote a shift of K⁺ into versus out of cells: 

Into cells	Out of cells

Into cells	Out of cells
Insulin + Dextrose (1st line treatment)	Cell lysis (hemolysis, rhabdomyolysis, tumor lysis)
BAR agonists	Hyperosmolality
Alkalosis	Acidosis
Aldosterone (chronic)	Exercise
Sodium bicarbonate	B-Blockers

What percent of potassium excretion normally occurs via the kidney versus the GI tract, and under what condition does GI excretion become more important?

Potassium Excretion: 90% 

GI Excretion: 10% 

GI excretion becomes more important in renal impairment. 

Complete the table describing renal K⁺ reabsorption:

Nephron Segment	Approximate K⁺ Reabsorbed	Primary Mechanism
Proximal tubule
Thick ascending limb

Nephron Segment	Approximate K⁺ Reabsorbed	Primary Mechanism
Proximal tubule	65%	K + is reabsorbed via the paracellular route (in between cells)
Thick ascending limb	25%	K + is transported actively via NKCC2 then K + /Cl cotransporter

In the distal tubule and collecting duct, K⁺ secretion is regulated by the coordinated activity of the [], [], and []. [] enhances K⁺ secretion by increasing the expression and activity of these transporters and channels.

In the distal tubule and collecting duct, K⁺ secretion is regulated by the coordinated activity of the Basolateral Na+/K+/ATPase, apical Na+ channel (ENaC), and apical K+ channel. Aldosterone enhances K⁺ secretion by increasing the expression and activity of these transporters and channels. 

Normal serum potassium: _ mEq/L
Mild hypokalemia: _ mEq/L	Mild hyperkalemia: _ mEq/L
Moderate hypokalemia: _ mEq/L	Moderate hyperkalemia: _ mEq/L
Severe hypokalemia: _ mEq/L	Severe hyperkalemia: _ mEq/L

Normal serum potassium: 3.5-5.0 mEq/L
Mild hypokalemia: 3.1-3.49 mEq/L	Mild hyperkalemia: 5.1–5.9 mEq/L
Moderate hypokalemia: 2.5-3 mEq/L	Moderate hyperkalemia: 6.0–7 mEq/L
Severe hypokalemia: <2.5 mEq/L	Severe hyperkalemia: >7 mEq/L

Hypokalemia	Hyperkalemia
~~ekg changes

Hypokalemia	Hyperkalemia
Flattened T wave	Peaked T waves (early indicator)
Prolonged PR and QT	Widened QRS
Prominent U wave	Loss of P wave
ST Depression	Sine wave pattern (impending arrest)

Cardiac arrhythmias in hypokalemia vs hyperkalemia

Hypokalemia: Torsades De Pointes, V tach, V fib, ventricular ectopy

Hyperkalemia: Asystole, bradycardia, AV block, V fib

Hypokalemia is associated with diarrhea/constipation and metabolic [], while hyperkalemia is associated with diarrhea/constipation and metabolic []. 

Alkalosis

Acidosis

How does Mg2+ exist intracellularly and extraceullarly?

• Intracellular: Bone (67%) and muscle (20%)

  • Extracellular: Ionized form, with just 20% existing as bound to serum protein

What increases renal excretion of Mg2+?

• Loop and thiazide diuretics

• Nephrotoxin agents that impair tubule function

• Chronic alcohol (AUD)

• Hypercalcemia

• Metabolic acidosis

• Gitelman syndrome, Bartter syndrome (specific genetic disorders)

What reduces intestial absorption of Mg2+?

• Celiac disease or Crohn’s disease

• Chronic diarrhea

• Intestinal resection

• PPIs and antacids

• Age

T/F: You must correct the hypokalemia before trying to correct the hypomagnesemia

F → Switch d/t

ROMK channels in the thick ascending limb and distal tubule secrete intracellular K+ into the urine → Mg2+ normally inhibits ROMK channels, so a drop in Mg2+ levels means loss of K+

What causes a decreased renal excretion of Mg2+?

CKD

AKI

What causes an excessive intake of Mg2+?

• Cathartics contain high Mg2+

• Hemiacidrin (ureteral irrigant for kidney stones)

• Magnesium sulfate (treatment of preeclampsia)

List Electrolytes and their Normal Ranges

. Which potassium oral supplement has the highest elemental potassium?

a. Potassium Bicarbonate 

b. Potassium Citrate 

c. Potassium Chloride 

d. Potassium Gluconate 

c. Potassium Chloride 

x

x

Hemodialysis → Can cause [] if dialysate K⁺ is low

Hypokalemia

Medications that can cause hypokalemia

Insulin, Albuterol, Loop/thiazide diuretics

Potassium Repletion Management for:

K+: 3.5-4 mEq/L

K+ 3-3.4 mEq/L

K+: <3 mEq/

K⁺ 3.5–4 mEq/L (Early depletion)

• No pharmacologic therapy, encourage dietary potassium intake

K⁺ 3–3.4 mEq/L

• Asymptomatic → may not need treatment

• Symptomatic → initiate oral K+

K⁺ <3 mEq/L → Always treat (goal 4–4.5 mEq/L)

• Oral preferred if asymptomatic

• IV if severe symptoms or unable to tolerate PO

What Potassium Oral Replacements should you use for the following situations?

1. Most common, effective for K⁺ and Cl⁻ losses

2. Hypokalemia with metabolic acidosis - alkanizing effect

3. Less common, generally mild hypokalemia. Use when chloride is elevated.

Potassium Oral Replacements

• Potassium Chloride

• Potassium Bicarbonate/Citrate

• Potassium Gluconate

Usual dose of K+ to PREVENT hypokalemia: [] mEq/day

Usual dose of K+ to TREAT hypokalemia: [] mEq/dose

20 mEq/day

40-100 mEq/dose

What IV Potassium Replacement should you use for the following situations?

1. Most common and efficient

2. Also has metabolic acidosis

3. Hypophosphatemia

1. Potassium chloride

2. Potassium acetate

3. Potassium phosphate

IV peripheral line & central line max rate & concentration

Never give [] as an IV push → Will cause cardiac arrest

K+

Medications that may cause Hyperkalemia

Digoxin

Management for hyperkalemia when underlying cause is metabolic acidosis

Sodium bicarbonate IV

Chronic Hyperkalemia Medications

Dietary

• Limit of potassium rich foods and supplements

Diuretics

• Furosemide IV:PO dose ratio (1:2)

• Avoid Potassium-sparing diuretics

Cation-exchangers

• Kayexalate (SPS), Veltassa, Lokelma (SZC)

Dialysis

• Adjust medications, and typically given after dialysis

Order of Operations Symptomatic

• 1. Protect the heart 

  • IV Calcium

    • IV Calcium Gluconate 1g (preferred) 

    • IV Calcium Cl- 

• 2. Shift K+ INTO cells 

  • 5-10 units regular Insulin (Humulin R) + Dextrose →  1st line

  • Sodium Bicarbonate IV 50-100 mEq 

    • Adjunctive in pts. w/ 

      • Metabolic acidosis

  • B2 agonists

    • Nebulized albuterol 10-20 mg over 10 mins 

• 3. K+ Elimination

  • IV Loop Diuretics

    • Furosemide 20-40 mg IV

  • Potassium Binders (Cation Exchange Resins) 

    • Kayexalate (SPS), Veltassa, Lokelma (SZC)

• 4. Dialysis 

  • Indicated for patients w/ AKI + EKG changes or refractory

For hyperkalemia management:

Drug	Onset	MOA
Calcium gluconate
Sodium bicarbonate
Insulin with dextrose
Furosemide
Albuterol
Sodium polystyrene sulfonate
Patiromer
Sodium Zirconium  Cyclosilicate

Drug	Onset	MOA
Calcium gluconate	<3 minutes	Antagonizes cardiac effects of hyperkalemia Raises myocardial threshold potential Reverses ECG changes quickly
Sodium bicarbonate	30 min	Raises serum pH, lowering K+
Insulin with dextrose	< 30 min	Insulin activates the Na+/K+ -ATPase pump and dextrose protects against low glucose
Furosemide	5-15 min	Inhibits renal Na+ reabsorption → Inc urinary K+ loss
Albuterol	30 min	B2 agonist
Sodium polystyrene sulfonate	~1 hour	Exchanges Na⁺ for K⁺ in the colon
Patiromer	7-24 hours (delayed)	Exchanges Ca²⁺ for K⁺ in the distal colon
Sodium Zirconium  Cyclosilicate	~1 hour	Exchanges Na⁺ for K⁺ throughout GI tract

Dextrose must precede [] to avoid hypoglycemia

Dextrose must precede insulin to avoid hypoglycemia

• 5-10* units regular insulin IVP + 25*-50 g dextrose IV

Nurse asks what albuterol dose to give for hyperkalemia. Standard asthma nebulizer is 2.5 mg. What dose do you recommend and how long to nebulize?

A) 2.5 mg over 5 minutes B) 5 mg over 5 minutes C) 10–20 mg over 10 minutes D) 0.5 mg IV push

C) 10–20 mg over 10 minutes

If a provider wants to order SPS STAT for a patient with a K⁺ of 6.9 and peaked T waves, how would you respond as the pharmacist?

Nah bro this shit is emergent and SPS stat has too long of an onset

Do last patient case and practice problems

What cardiac arrhythmias can results from hypomagnesemia?

Vfib + Torsade de pointes

EKG Changes in severe hypomagnesemia

• Prolonged PR interval

• Widening of QRS complex

• Flattened T wave