Outline

Chapter 14

- Hypovolemic States

- Etiology

- True volume depletion occurs when fluid is lost from from the extracellular fluid at a rate exceeding intake

- Can come the GI tract

- Lungs

- Urine

- Sequestration in the body in a “third space” that is not in equilibrium with the extracellular fluid.

- When losses occur two responses ameliorate them

- Our intake of Na and fluid is way above basal needs

- This is not the case with anorexia or vomiting

- The kidney responds by minimizing further urinary losses

- This adaptive response is why diuretics do not cause progressive volume depletion

- Initial volume loss stimulates RAAS, and possibly other compensatory mechanisms, resulting increased proximal and collecting tubule Na reabsorption.

- This balances the diuretic effect resulting in a new steady state in 1-2weeks

- New steady state means Na in = Na out

- GI Losses

- Stomach, pancreas, GB, and intestines secretes 3-6 liters a day.

- Almost all is reabsorbed with only loss of 100-200 ml in stool a day

- Volume depletion can result from surgical drainage or failure of reabsorption

- Acid base disturbances with GI losses

- Stomach losses cause metabolic alkalosis

- Intestinal, pancreatic and biliary secretions are alkalotic so losing them causes metabolic acidosis

- Fistulas, laxative abuse, diarrhea, ostomies, tube drainage

- High content of potassium so associated with hypokalemia

- [This is a mistake for stomach losses]

- Bleeding from the GI tract can also cause volume depletion

- No electrolyte disorders from this unless lactic acidosis

- Renal losses

- 130-180 liters filtered every day

- 98-99% reabsorbed

- Urine output of 1-2 liters

- A small 1-2% decrease in reabsorption can lead to 2-4 liter increase in Na and Water excretion

- 4 liters of urine output is the goal of therapeutic diuresis which means a reduction of fluid reabsorption of only 2%

- Diuretics

- Osmotic diuretics

- Severe hyperglycemia can contribute to a fluid deficit of 8-10 Iiters

- CKD with GFR < 25 are poor Na conservers

- Obligate sodium losses of 10 to 40 mEq/day

- Normal people can reduce obligate Na losses down to 5 mEq/day

- Usually not a problem because most people eat way more than 10-40 mEq of Na a day.

- Salt wasting nephropathies

- Water losses of 2 liters a day

- 100 mEq of Na a day

- Tubular and interstitial diseases

- Medullary cystic kidney

- Mechanism

- Increased urea can be an osmotic diuretic

- Damage to tubular epithelium can make it aldo resistant

- Inability to shut off natriuretic hormone (ANP?)

- The decreased nephro number means they need to be able to decrease sodium reabsorption per nephron. This may not be able to be shut down acutely.

- Experiment, salt wasters can stay in balance if sodium intake is slowly decreased. (Think weeks)

- Talks about post obstruction diuresis

- Says it is usually appropriate rather than inappropriate physiology.

- Usually catch up solute and water clearance after releasing obstruction

- Recommends 50-75/hr of half normal saline

- Talks briefly about DI

- Skin and respiratory losses

- 700-1000 ml of water lost daily by evaporation, insensible losses (not sweat)

- Can rise to 1-2 liters per hour in dry hot climate

- 30-50 mEq/L Na

- Thirst is primary compensation for this

- Sweat sodium losses can result in hypovolemia

- Burns and exudative skin losses changes the nature of fluid losses resulting in fluid losses more similar to plasma with a variable amount of protein

- Bronchorrhea

- Sequestration into a third space

- Volume Deficiency produced by the loss of interstitial and intravascular fluid into a third space that is not in equilibrium with the extracellular fluid.

- Hip fracture 1500-2000 into tissues adjacent to fxr

- Intestinal obstruction, severe pancreatitis, crush injury, bleeding, peritonitis, obstruction of a major venous system

- Difference between 3rd space and cirrhosis ascities

- Rate of accumulation, if the rate is slow enough there is time for renal sodium and water compensation to maintain balance.

- So cirrhotics get edema from salt retension and do not act as hypovolemia

- Hemodynamic response to volume depletion

- Initial volume deficit reduced venous return to heart

- Detected by cardiopulmonary receptors in atria and pulmonary veins leading to sympathetic vasoconstriction in skin and skeletal muscle.

- More marked depletion will result in decreased cardiac output and decrease in BP

- This drop in BP is now detected by carotid and aortic arch baroreceptors resulting in splanchnic and renal circulation vasoconstriction

- This maintains cardiac and cerebral circulation

- Returns BP toward normal

- Increase in BP due to increased venous return

- Increased cardiac contractility and heart rate

- Increased vascular resistance

- Sympathetic tone

- Renin leading to Ang2

- These can compensate for 500 ml of blood loss (10%)

- Unless there is autonomic dysfunction

- With 16-25% loss this will not compensate for BP when patient upright

- Postural dizziness

- Symptoms

- Three sets of symptoms can occur in hypovolemic patients

- Those related to the manner in which the fluid loss occurs

- Vomiting

- Diarrhea

- Polyuria

- Those due to volume depletion

- Those due to the electrode and acid base disorders that can accompany volume depletion

- The symptoms of volume depletion are primarily related to the decrease in tissue perfusion

- Early symptoms

- Lassitude

- Fatiguability

- Thirst

- Muscle cramps

- Postural dizziness

- As it gets more severe

- Abdominal pain

- Chest pain

- Lethargy

- Confusion

- Symptomatic hypovolemia is most common with isosmotic Na and water depletion

- In contrast pure water loss, causes hypernatremia, which results in movement of water from the intracellular compartment to the extracellular compartment, so that 2/3s of volume loss comes from the intracellular compartment, which minimizes the decrease in perfusion

- Electrolyte disorders and symptoms

- Muscle weakness from hypokalemia

- Polyuria/poly dips is from hyperglycemia and hypokalemia

- Lethargy, confusion, Seizures, coma from hyponatremia, hypernatremia, hyperglycemia

- Extreme salt craving is unique to adrenal insufficiency

- Eating salt off hands ref 18

- Evaluation of the hypovolemic patient

- Know that if the losses are insensible then the sodium should rise

- Volume depletion refers to extracellular volume depletion of any cause, while dehydration refers to the presence of hypernatremia due to pure water loss. Such patients are also hypovolemic.

- Physical exam is insensitive and nonspecific

- Finding most sensitive and specific finding for bleeding is postural changes in blood pressure

- I don’t find this very specific at all!

- Recommends laboratory confirmation regardless of physical exam

- Skin and mucous membranes

- Should return too shape quickly

- Elastic property is called Turgur

- Not reliable is patients older than 55 to 60

- Dry axilla

- Dry mucus membranes

- Dark skin in Addison’s disease Frim increased ACTH

- Arterial BP

- As volume goes down so does arterial BP

- Marked fluid loss leads to quiet korotkoff signs

- Interpret BP in terms of the patients “normal BP”

- Venous pressure

- Best done by looking at the JVP

- Right atrial and left atrial pressure

- LV EDP is RAP + 5 mmHg

- Be careful if valvular disease, right heart failure, cor pulmonare,

- Figure 14-2

- Shock

- 30% blood loss

- Lab Data

- Urine Na concentration

- Should be less than 25 mmol/L, can go as low as 1 mmol/L

- Metabolic alkalosis can throw this off

- Look to the urine chloride

- Figure 14-3

- Renal artery stenosis can throw this off

- FENa

- Mentions that it doesn’t work so well at high GFR

- Urine osmolality

- Indicates ADH

- Volume depletion often associated with urine osm > 450

- Impaired by

- Renal disease

- Osmotic diuretic

- Diuretics

- DI

- Mentions that severe volume depletion and hypokalemia impairs urea retension in renal medulla

- Points out that isotonic urine does not rule out hypovolemia

- Mentions specific gravity

- BUN and Cr concentration

- Normal ratio is 10:1

- Volume depletion this goes to 20:1

- Serum Na

- Talks about diarrhea

- Difference between secretory diarrhea which is isotonic and just causes hypovolemia

- And osmotic which results in a lower electrolyte content and development of hypernatremia

- Talks about hyperglycemia

- Also can cause the sodium to rise from the low electrolyte content of the urine

- But the pseudohyponatraemia can protect against this

- Plasma potassium

- Treatment

- Both oral and IV treatment can be used for volume replacement

- The goal of therapy are to restore normovolemia

- And to correct associated acid-base and electrolyte disorders

- Oral Therapy

- Usually can be accomplished with increased water and dietary sodium

- May use salt tablets

- Glucose often added to resuscitation fluids

- Provides calories

- Promotes intestinal Na reabsorption since there is coupled Na and Glucose similar to that seen in the proximal tubule

- Rice based solutions provide more calories and amino acids which also promote sodium reabsorption

- 80g/L of glucose with rice vs 20 g/L with glucose alone

- IV therapy

- Dextrose solutions

- Physiologically equivalent to water

- For correcting hypernatremia

- For covering insensible losses

- Watch for hyperglycemia

- Footnote warns against giving sterile water

- Saline solutions

- Most hypovolemic patients have a water and a sodium deficit

- Isotonic saline has a Na concentration of 154, similar to that of plasma see page 000

- Half-isotonic saline is equivalent to 550 ml of

isotonic saline and 500 of free water. Is that a typo?

- 3% is a liter of hypertonic saline and 359 extra mEq of Na

- Dextrose in saline solutions

- Give a small amount of calories, otherwise useless

- Alkalinizing solutions

- 7.5% NaHCO3 in 50 ml ampules 44 mEq of Na and 44 mEq of HCO3

- Treat metabolic acidosis or hyperkalemia

- Why 44 mEq and not 50?

- Do not give with calcium will form insoluble CaCO3

- Polyionic solutions

- Ringers contains physiologic K and Ca

- Lactated Ringers adds 28 mEq of lactate

- Spreads myth of LR in lactic acidosis

- Potassium chloride

- Available as 2 mEq/mL

- Do not give as a bolus as it can cause fatal hyperkalemia

- Plasma volume expanders

- Albumin, polygelastins, hetastarch are restricted to vascular space

- 25% albumin can pull fluid into the vascular space

- 25% albumin is an albumin concentration of 25 g/dL compare to physiologic 4 g/dL

- Says it pulls in several times its own volume

- 5% albumin is like giving plasma

- Blood

- Which fluid?

- Look at osmolality, give hypotonic fluids to people with high osmolality

- Must include all electrolytes

- Example of adding 77 mEw of K to 0.45 NS and making it isotonic

- DI can be replaced with dextrose solutions, pure water deficit

- Case 14-3

- Diarrhea with metabolic acidosis

- He chooses 0.25 NS with 44 mEq of NaCl and 44 NaHCO3

- Talks about blood and trauma

- Some studies advocate delaying saline until penetrating trauma is corrected APR about to. Keep BP low to prevent bleeding. Worry about diluting coagulation factors

- Only do this if the OR is quickly available

- Volume deficit

- Provides formula for water deficit and sodium deficit

- Do not work for isotonic losses

- Provides a table to adjust fluid loss based on changes in Hgb or HCTZ

- Says difficult to estimate it from lab findings and calculations

- Follow serial exams

- Serial urine Na

- Rate of replacement

- Goal is not to give fluid but to induce a positive balance

- Suggests 50-100 ml/hr over what is coming out of the body

- Urine

- Insensibles 30-50

- Diarrhea

- Tubes

- Hypovolemic shock

- Due to bleeding

- Sequesting in third space

- Why shock?

- Progressive volume depletion leads to

- Increased sympathetic NS

- Increased Ang 2

- Initially this maintains BP, cerebral and coronary circulation

- But this can decrease splanchnic, renal and mucocutaneous perfusion

- This leads to lactic acicosis

- This can result in intracellular contents moving into circulation or translocation of gut bacteria

- Early therapy to prevent irreversible shock

- In dogs need to treat with in 2 hours

- In humans may need more than 4 hours

- Irreversible shock associated with pooling of blood in capillaries

- Vasomotor paralysis

- Hyperpolarization of vascular smooth muscle as depletion of ATP allows K to flowing out from K channels opening. Ca flows out too leading to vasodilation

- Glyburide is an K-ATP channel inhibitor (?) caused increased vasoconstriction and BP

- Pluggin of capillaries by neutrophils

- Cerebral ischemia

- Increased NO generation

- Which Fluids?

- Think of what is lost and replace that.

- Bleeding think blood

- Raise the hct but not above 35

- Acellular blood substitutes, looked bad at the time of this writing

- Di aspirin cross linked hemoglobin had increased 2 and 28 day mortality vs saline

- Colloids sound great but they fail in RCTs

- SAFE

- FEAST

- Points out that saline replaces the interstitial losses why do we think those losses are unimportant

- Pulmonary circulation issue

- Pulmonary circulation is more leaky so oncotic pressure less effective there

- Talks about the lungs be naturally protected from pulmonary edema

- Rate of fluid

- 1-2 liters in first hour

- Suggests CVP or capillary wedge pressure during resuscitation

- No refs in the rate of fluid administration section

- Lactic acidosis

- Points out that HCO can impair lactate utilization

- Also states that arterial pH does not point out what is happening at the tissue level. Suggests mixed-venous sample.

References

JCI - Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia and a nice review of this topic: Altered Prostaglandin Signaling as a Cause of Thiazide-Induced Hyponatremia

The electrolyte concentration of human gastric secretion. https://physoc.onlinelibrary.wiley.com/doi/10.1113/expphysiol.1960.sp001428

A classic by Danovitch and Bricker: Reversibility of the “Salt-Losing” Tendency of Chronic Renal Failure | NEJM

Osmotic Diuresis Due to Retained Urea after Release of Obstructive Uropathy | NEJM

Is This Patient Hypovolemic? | Cardiology | JAMA
And by the same author, a textbook: Steven McGee. 5th edition. Evidence-Based Physical Diagnosis Elsevier Philadelphia 2022. ISBN-13: 978-0323754835

The clinical course and pathophysiological investigation of adolescent gestational diabetes insipidus: a case report | BMC Endocrine Disorders

Sensitivity and specificity of clinical signs for assessment of dehydration in endurance athletes | British Journal of Sports Medicine

Diagnostic performance of serum blood urea nitrogen to creatinine ratio for distinguishing prerenal from intrinsic acute kidney injury in the emergency department | BMC Nephrology

The meaning of the blood urea nitrogen/creatinine ratio in acute kidney injury - PMC

Language guiding therapy: the case for dehydration vs volume depletion https://www.acpjournals.org/doi/10.7326/0003-4819-127-9-199711010-00020?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Validation of a noninvasive monitor to continuously trend individual responses to hypovolemia

References for Anna’s voice of God on Third Spacing :  Shires Paper from 1964  (The ‘third space’ – fact or fiction? )

References for melanie’s VOG:

1. Appraising the Preclinical Evidence of the Role of the Renin-Angiotensin-Aldosterone System in Antenatal Programming of Maternal and Offspring Cardiovascular Health Across the Life Course: Moving the Field Forward: A Scientific Statement From the American Heart Association

2. excellent review of RAAS in pregnancy: The enigma of continual plasma volume expansion in pregnancy: critical role of the renin-angiotensin-aldosterone system

https://journals-physiology-org.ezp-prod1.hul.harvard.edu/doi/full/10.1152/ajprenal.00129.2016

3. 10.1172/JCI107462- classic study in JCI of AngII responsiveness during pregnancy

4. William’s Obstetrics 26th edition!

5. Feto-maternal osmotic balance at term. A prospective observational study