Renal 04: Clinical Correlations To Renal Phys And Dz

Front 1

How is water balance, and therefore serum Na+, maintained in setting of increased water intake?

Back 1

Excretion of dilute urine

Front 2

What are the ways to lose water?

Back 2

Fixed Water Excretion / total insensible losses: 0.5 L/day
- Stool (0.1 L/day)
- Sweat (0.1 L/day)
- Pulmonary (0.3 L/day)

Variable Water Excretion:
- Urine (1.0 - 1.5 L/day)

Front 3

What is osmolarity?

Back 3

Total solute / ECF volume

Front 4

What are the approximate concentrations of K+ and Na+ intracellularly?

Back 4

K+: 140 mEq/L
Na+: 10 mEq/L

Front 5

What are the approximate concentrations of K+ and Na+ extracellularly?

Back 5

K+: 4 mEq/L
Na+: 140 mEq/L

Front 6

What is the primary determinant of extracellular fluid osmolarity?

Back 6

** Na+ concentration (140 mEq/L)

Front 7

How does a hypertonic osmolarity return to isotonicity?

Back 7

- Stimulates hypothalamic receptors
- ↑ Thirst → ↑ Water intake
- ↑ ADH release → Renal water retention

Causes return to isotonicity

Front 8

How does a hypotonic osmolarity return to isotonicity?

Back 8

- Inhibits hypothalamic receptors
- ↓ Thirst → ↓ Water intake
- ↓ ADH release → Renal water excretion

Causes return to isotonicity

Front 9

What receptors control stimuli for ADH release? How?

Back 9

- Osmoreceptors: ↑ plasma Osm → ↑ ADH
- Baroreceptors: ↑ volume depletion → ↑ ADH

Front 10

How does osmolarity relate to ADH release? What receptors control this?

Back 10

- As plasma osmolarity increases above 280, ADH release into plasma increases
- Controlled by osmoreceptors

Front 11

How does blood volume relate to ADH release? What receptors control this?

Back 11

- As % blood volume depletion increases above 5%, ADH release into plasma increases
- Controlled by baroreceptors

Front 12

Where is the tubular fluid the most concentrated (highest osmolarity?

Back 12

- Loop of Henle
- Medullary collecting duct (depending on amount of ADH)

Front 13

Where is the tubular fluid the least concentrated (highest osmolarity?

Back 13

- Distal Tubule
- Cortical Collecting Tubule / Duct

Front 14

How does ADH affect urine osmolarity?

Back 14

- The more ADH there is, the greater the urine osmolarity (up to 1200)
- The less ADH there is, the lower the urine osmolarity (as low as 50)

Front 15

Why did the woman in the water drinking contest die?

Back 15

- Her serum Na+ was estimated to be 114 mEq/L (normal is 135 - 145 mEq/L)
- She overrode her decrease thirst mechanism, so continued to dilute her Na+ / hypotonic fluid

Front 16

What are the signs and symptoms of Hyponatremia?

Back 16

- Nausea / vomiting
- Weakness
- Headache
- Lethargy
- Seizures
- Respiratory depression
- Death

Front 17

What factors alter water balance?

Back 17

- ADH (appropriate or inappropriate)
- Water intake
- Altered renal water handling

Front 18

What can cause inappropriate secretion of ADH?

Back 18

- Cancer (eg, small cell lung)
- CNS disease
- Pulmonary disease
- Drugs: narcotic, anti-emetics, SSRIs
- HIV

Front 19

How is ECF osmolarity regulated?

Back 19

Tightly by changes in thirst and ADH secretion

Front 20

How does the kidney prevent hypo-osmolarity d/t increased water intake?

Back 20

Excretes a dilute urine (osm < 100 mOsm/kg)

Front 21

What effects can inappropriately elevated ADH have?

Back 21

- Hyponatremia
- Hypo-osmolarity since urinary dilution is impaired (osm > 300 mOsm/kg)

Front 22

What is the GFR? Normal values?

Back 22

-Amount of plasma filtered through glomeruli per unit time
- Normal: ~90 - 125 mL/min

Front 23

What is BUN? Function?

Back 23

- Blood Urea Nitrogen, nitrogenous waste product of protein metabolism
- Less accurate indicator of GFR than creatinine d/t variation in protein intake, catabolic rate, tubular reabsorption
- Useful in conjunction w/ creatinine in differential diagnosis of renal disease

Front 24

Why is BUN less accurate of an indicator of GFR than creatinine?

Back 24

BUN levels vary d/t:
- Protein intake
- Catabolic rate
- Tubular reabsorption

Front 25

What is Creatinine? Why is it useful for estimating GFR?

Back 25

- Breakdown product of skeletal muscle
- Production remains constant over time
- Filtered at glomerulus

Front 26

Why is creatinine less accurate of an indicator of GFR than inulin?

Back 26

- Creatinine is also secreted in nephron
- Creatinine clearance therefore overestimates GFR

Front 27

What are the limitations of creatinine for determining GFR?

Back 27

- Creatinine is also secreted in nephron
- Creatinine clearance therefore overestimates GFR
- Differences in individual muscle mass affect creatinine clearance

Front 28

How can you very roughly estimate GFR if you know creatinine?

Back 28

GFR ~ 100 / Cr

E.g., Serum Cr of 1 → GFR = 100
E.g., Serum Cr of 2 → GFR = 50
E.g., Serum Cr of 3 → GFR = 33

Front 29

When is a change in serum creatinine more serious?

Back 29

When the change is a greater percentage of the total creatinine it has a greater impact on GFR
E.g., change from 1 to 1.5 is more serious than 3 to 3.5

Front 30

How can you use inulin values to calculate GFR?

Back 30

GFR = Uinulin * V / Pinulin

Front 31

What is the Cockcroft-Gault equation used for?

Back 31

Estimating GFR from serum creatinine (takes into account age, weight, and gender too)

Front 32

What are the ways to calculate Creatinine Clearance?

Back 32

- CrCl = U*V/P
- Cockcroft - Gault equation

Front 33

Why are serum creatinine based GFR estimates sometimes inaccurate?

Back 33

Extremes in age, BMI, or muscle mass

Front 34

Which of the following does not contribute to systemic response to extracellular fluid volume depletion?
- increased reabsorption of Na+ at PT
- decreased renal nerve activity
- increase ADH secretion
- activation of baroreceptors

Back 34

Decreased renal nerve activity

Front 35

What factors contribute to systemic response to extracellular fluid volume depletion?

Back 35

- Baroreceptor activation (increased sympathetic tone)
- Increased renin secretion
- Increased AngII / increased Aldosterone = increased tubular Na reabsorption

Front 36

What are the direct tubular effects on Na+ reabsorption?

Back 36

Renal sympathetic nerves:
- multiple tubular receptors stimulate Na+ reabsorption

Angiotensin II:
- tubular receptors
- increases activity of PT Na/H counter-transporter

Aldosterone:
- stimulates Na+ reabsorption in cortical collecting duct principal cells
- increases number of luminal Na+ channels and BL Na/K-ATPases

Front 37

What percentage of filtered load of Na+ has its excretion dependent on aldosterone action?

Back 37

~2%

Front 38

What controls Aldosterone secretion?

Back 38

Angiotensin II:
- most important stimulus for aldosterone secretion relating to Na balance
- AngII is dependent upon renin secretion and therefore baroreceptors, macula densa, and renal sympathetic tone

Front 39

What is the action of ADH? Where?

Back 39

- Binds to V2 receptors on cells in late distal tubule, collecting tubules, and collecting ducts
- Leads to increased Aquaporin-2 (AQP-2) channels on the tubular lumen side to increase reabsorption of H2O
- Mediated via ↑cAMP, activation of PKA, and protein phosphorylation

Front 40

What should be done to treat a patient with volume depletion due to nausea, vomiting, and diarrhea?

Back 40

- Give normal saline (150 cc/hour IV)
- Anti-emetics
- Increase oral fluid intake

Front 41

What does the systemic response to decreased ECF volume involve? Implications?

Back 41

- Baroreceptor and sympathetic nerve activation
- Activation of Renin-AngII-Aldo system
- Increased ADH

- Leads to enhanced renal tubular Na+ and H2O reabsorption (leads to low urine Na+, low FENa, and elevated urine osmolarity)

Front 42

28 yo male w/ 20y hx of CKD d/t vesicoureteral reflux presents w/ weakness, bone pain, headaches, blurred vision, and nausea. BP 220/160. Ill appearing, pale sclera and nail beds, flow murmur LLSB, knobby knees/ankles w/ valgus knee deformity, ↑ DTRs w/ clonus.
Labs: Hct 7 g/dl, serum creatinine 16 mg/dl, BUN 180 mg/dl, Ca 6.5 mg/dl, phosphorus 11 mg/dl, PTH 1200 (11-54 pg/ml)

What factor contributes to his parathyroidism?

Back 42

Increased serum phosphorus

Front 43

What stimulates PTH release?

Back 43

- Low Ca2+
- High Phosphorus

Front 44

What are the endocrine functions of the kidney?

Back 44

- Renin release from juxtaglomerular cells
- Erythropoetin (epo) produced by renal cortical tubular cells, stimulates RBC production in marrow
- 1,25-dihydroxy-vitamin D production formed in proximal tubule cells, regulates calcium and phosphate balance

Front 45

What are the effects of increased PTH?

Back 45

- ↑ Vitamin D3 activation → ↑ intestinal Ca2+ reabsorption
- ↑ Renal Ca2+ reabsorption
- ↑ Ca2+ release from bones

Front 46

How are calcium and phosphorus affected by kidney disease?

Back 46

- ↑ Serum PO4 (increased retention)
- ↓ 1,25-Dihydroxy-Vitamin D
- ↓ Serum Ca2+

- Decreased calcitriol production ↓ Ca2+ absorption, hypocalcemia

Leads to ↑PTH release (2° Hyperparathyroidism)