9/10- Clinical Approach to Body Volume Disturbances

Question 1

What is normal ECF osmolality? Na?

Answer 1

Na = 140 mEq/L

Osm = 285 mOsm/kg

Question 2

What is normal ICF osmolality? K?

Answer 2

K = 140 mEq/L

Osm = 285 mOsm/kg

Question 3

What is the equation for plasma osmolality?

Answer 3

2Na + glucose/18 + BUN/2.8

Question 4

Water balance (pictures)

Answer 4

Question 5

How is total body water regulated?

Answer 5

• Thirst
• ADH
• The kidneys

Question 6

What are the functions of angiotensin II?

Answer 6

1. Stimulates production of aldosterone
2. Acts directly on arterioles to cause vasoconstriction
3. Stimulates Na+/H+ exchange in the proximal tubule
4. Stimulates thirst center

Question 7

What are the functions of aldosterone?

Answer 7

1. Stimulates reabsorption of Na+ and excretion of K+ in the late distal tubule and collecting tubule.
2. Stimulates activity of H+ ATPase pumps in the late distal tubule and collecting tubule.

Also:

• Increases the water permeability of the collecting tubule
• Mildly increases vascular resistance

Question 8

Where is ADH made? How is release regulated?

Answer 8

• Synthesized in the hypothalamus and stored in the posterior pituitary
• Released in response to plasma hyperosmolality and decreased effective circulating volume

Question 9

What is the driving force for glomerular filtration rate (GFR)?

Answer 9

Hydrostatic pressure

Question 10

What drugs affect GFR?

Answer 10

Drugs that regulate RBF

• Xanthines (caffeine, theophylline, aminophylline) increase CO and vasodilation, resulting in increased RBF

Question 11

T/F: Filtration is a nonselective process

Answer 11

True

Question 12

What determines filtration (factors)?

Answer 12

Function of:

• GBM permeability
• Net filtration pressure across the capillaries

Question 13

What types of substances undergo filtration? What remains in the blood?

Answer 13

• All small molecules (electrolytes, AAs, glucose, drugs and metabolic waste) undergo filtration
• Cells and large molecules (lipids and proteins) remain in the blood

Question 14

How many L get filtered per day? What are the main ions?

Answer 14

• 180 L/day filtered
• Mostly Na, Cl and bicarbonate ions

Question 15

What is normal GFR?

Answer 15

~120 mL/min

Question 16

More than __ of filtered water and electrolytes are reabsorbed

Answer 16

More than 99% of filtered water and electrolytes are reabsorbed

Question 17

T/F: water is actively reabsorbed to prevent excessive loss following filtration

Answer 17

False

• Water follows passively (facilitated by water channels AQPs) along the osmotic gradient created by solute reuptake

Question 18

T/F: Many solutes undergo active transport to be reabsorbed

Answer 18

True

• AA, glucose, phosphate, electrolytes… etc

Question 19

What are the two main kinds of “pumps” used in active tubular secretion?

Answer 19

• For organic acids (uric acid, p-aminohippuric acid, diuretics, antibiotics, etc…)
• For organic bases (creatinine, procainamide, choline, etc…)

Question 20

Where does the process of active tubular secretion mainly take place?

Answer 20

Proximal tubule

Question 21

What are the main ion handling functions of the proximal tubule?

Answer 21

• 60% of total NaCl and water reabsorbtion
• 85% of total NaHCO3 reabsorption occurs in the early PT (dependent upon carbonic anhydrase)
• Organic acid/base secretion

Question 22

There are competitive interactions between diuretics and what?

Answer 22

Uric acid (probenecid) and other organic compounds (may impact diuretic action)

Question 23

What happens in the tDL?

Answer 23

• Does NOT participate in salt reabsorption
• Passive flux of water through AQP1 (driven by high medullary osmolality)

Question 24

What happens in the TAL?

Answer 24

Dilution and concentration segment

• Responsible for 25% of NaCl reabsorption
• Impermeable to water
• NaCl transport system: Na.K.2Cl cotransporter (the target of loop diuretics)
• Major site of Mg and Ca reabsorption

Solute removal without water uptake results in urine dilution

NaCl uptake increases the medullary interstitial osmolality and contributes to the concentrating mechanism

Question 25

What happens in the DCT?

Answer 25

_**Diluting** segment_ - Water **impermeable** - Responsible for **5-10% NaCl re-absorption** - NaCl transporter is **blocked by thiazide** diuretics - Aldosterone exerts a significant influence on NaCl co-transporter (Volume depletion) - **Ca** is actively **reabsorbed** (this process is regulated by parathyroid hormone)

Question 26

What happens in the collecting duct?

Answer 26

- Responsible for 2-5% of Na re-absorption - Na transport is mediated by Na channels in principal cells (stimulated by aldosterone) - Major site of **potassium (K+) secretion** (negatively charged lumen) - **ADH increases water permeability in collecting tubule**, through its action on AQP2, causing concentrated urine (ADH determines final urine concentration)

Question 27

Na and H2O transporters along nephron (picture)

Answer 27

Question 28

What may cause fluid deficiency (main causes)? Fluid excess?

Answer 28

_Deficiency:_ - Volume depletion (hypovolemia) - Dehydration _Excess:_ - Volume excess - Hypotonic hydration

Question 29

What may cause volume depletion?

Answer 29

**GI losses**: - Nausea - Vomiting - Diarrhea **Renal losses**: diuretics **Skin or Respiratory losses**: burns **Third Spacing** - Intestinal obstruction - Pancreatitis.

Question 30

What history might a pt present with in the cause of volume depletion?

Answer 30

Thirst, easy fatiguability, muscle cramps, postural dizziness. More severe fluid loss can lead to - chest pain, (coronary ischemia) - abdominal pain (mesentric ) - lethargy and confusion (cerebral vascular beds) Weight loss

Question 31

Clinical signs of volume depletion?

Answer 31

- Dry skin including axilla - Decreased skin turgor - Dry mucus membranes - Thready pulse, low arterial blood pressure - Orthostatic hypotension - Decreased jugular venous distension

Question 32

Lab abnormalities seen with volume depletion?

Answer 32

- Elevated BUN/CR ratio - Decreased urine Sodium - FeNa – Fractional excretion of sodium. - Hemoconcentration

Question 33

Therapy for volume depletion?

Answer 33

Isotonic IVF - Normal saline- 0.9% NaCl

Question 34

What is seen in volume overload state

Answer 34

Edema- palpable swelling produced by expansion of the interstitial fluid volume - Dependent bilateral edema - Lymphedema - Myxedema - Localized edema

Question 35

What is the pathophysiology of edema?

Answer 35

- An alteration in capillary hemodynamics that favors the movement of fluid from the vascular space into the interstitium. - The retention of sodium and water by the kidneys.

Question 36

The exchange of fluid between the plasma and the interstitium is determined by what?

Answer 36

Hydraulic and oncotic pressures. Starling's Law: Net filtration = LpS x (Δ hydraulic pressure - Δ oncotic pressure) = LpS x [(Pcap - Pif) - s(nx cap - nif)]

Question 37

What factors cause edema/volume overload?

Answer 37

**1. Increased venous pressure** - Blood volume expansion (heart failure, renal disease) - Venous obstruction (hepatic cirrhosis, deep venous thrombosis) **2. Hypoalbuminemia** - Loss of albumin in urine (nephrotic syndrome) - Decreased hepatic albumin synthesis (hepatic cirrhosis) **3. Increased capillary permeability** - Burns - ARDS - Malnutrition syndrome - Idiopathic capillary leak syndrome **4. Lymphatic obstruction (lymphedema)** - Primary: genetic defect - Secondary: radiation, parasites **5. Renal sodium retention** - Inability to excrete the Na and water (pts with kidney disease) - Appropriate compensatory response to effective circulating volume depletion, with urine Na under 20 meq/L

Question 38

Clinical manifestations of edematous states?

Answer 38

- Jugular vein distention - Pulmonary edema - Pleural effusions &/or pericardial effusions - Ascites - Edema of the lower extremities (\> 3L) - Puffy eyes - Dyspnea (pulmonary congestion): PND, DOE, Orthopnea

Question 39

Describe edema in heart failure: pathogenesis, effect on ions...

Answer 39

Perception of low effective arterial blood volume (EABV) due to heart failure - Activation of sympathetic nervous system, Renin-AII- Aldosterone and ADH. Na and water retention by the kidney - Urine studies - Low FENa, High SG

Question 40

Describe the problem with systolic heart failure. Treatment?

Answer 40

**Problem = Low EF** _Treatment:_ - Treat underlying causes - Na & water restriction - Diuretics ---- loop diuretics ---- Combination of loop diuretic and thiazide ---- Aldosterone antagonists - Digoxin - ACEi/Angiotensin II receptor blocker - Beta blockers - Vasodilator: Isosorbide and hydralazine

Question 41

Describe the problem with diastolic heart failure. Treatment?

Answer 41

**Problem = Inadequate LV filling** (normal EF) _Treatment:_ - Treat underlying causes - Control of HTN - Control of ventricular rate in patients with tachycardia - Control of edema with salt and water restriction and diuretics

Question 42

Describe the problem with cirrhosis: what is sensed? Ion handling?

Answer 42

Problem: - Perception of low EABV due to perpetual arteriolar vasodilatation (?NO, ?PGs). - As in CHF, sympathetic nervous system, Renin-AII-Aldosterone and ADH are activated. - Na & water retention follow (low FENA) - Hepatic flow obstruction favors the formation of ascites

Question 43

Treatment for edema in cirrhosis?

Answer 43

- Treat underlying causes of hepatic cirrhosis: ETOH, hepatitis - Na restriction, water restriction if SNa

Question 44

What is the problem with nephrotic syndrome (NS)?

Answer 44

(Nephrotic syndrome: problem with glomerulus so that pt is losing protein...) - Activation of the intra-renal renin/angiotensin system, with resultant Na & water retention. - The cause for activation of the renal AII-system is unknown. - Except in some children with nephrotic syndrome, the EABV is normal in spite of low serum albumin.

Question 45

Treatment in NS (nephrotic syndrome)?

Answer 45

- Treat the primary renal disease. - Na and water restriction. - High dose loop diuretic. - Combination of diuretics. - ACE inhibition is useful (reduce glomerular perfusion and thus proteinuria)

Question 46

What is the problem causing edema in renal failure and/or GN?

Answer 46

Problem = decreased GFR (decreased number of functioning nephrons), leading to diminished ability to eliminate Na load

Question 47

How to treat edema in renal failure and/or GN?

Answer 47

- Low salt diet - Diuretics

Question 48

Conclusions: - Disturbances of water balance reflect Dysnatremias. - Disturbances of volume ---- reflect sodium content abnormalities ---- involve abnormalities in Thirst mechanism, RAS and ADH. - Volume depletion – IVF – Saline - Volume overload – Low salt diet and Diuretics. ACEI in Nephrotic Syndrome.

Answer 48

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