Chapter Fourteen, part 1. Hypovolemic States
Channel Your Enthusiasm
Sodium Conservation in Chronic Kidney Disease
The chapter focuses on sodium conservation in patients with chronic kidney disease (CKD), discussing clinical observations and an experiment on urinary excretion. It also explores the concept of salt wasting nephropathy and the significance of low volume status in CKD patients.
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 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:
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
The AI-powered Podcast Player
