Fluid distribution and edema Edema, also spelled œdema, is an abnormal accumulation of fluid in the interstitium, located beneath the skin and in the cavities of the body, which can cause severe pain. Clinically, edema manifests as swelling. The amount of interstitial fluid is determined by the balance of fluid homeostasis; and the increased secretion of fluid into the interstitium, or the impaired removal of the fluid, can cause the condition. The word is from Greek οἴδημα oídēma meaning "swelling".

1. PHYSIOLOGY

2. FLUID DISTRIBUTION
• The body in divided in two compartment, and extracelular and intracelular
compartment separeted by the membranes
• Membrane = Barrier
• About 60% of the body mass is water
• Relationship ICF/ECF: 2/3:1/3
• Na+ stay ousite the extracellular compartment can cross the cell membrane
• ECF is divided in ISF and vascular membrane separeted by capillary
membrane
• ISF: Interstitial FLUID
• Vascular Volumen: Proteins (Albumin cant cross the capillary membrane

4. OSMOSIS
• mOsm/kg: concentration of particles per Kg of solvent
• Osmolarity = Osmolality
• Glucose effective osmole
• Effective osmole: Solute which cant cross the membrane is effective
causing the movement of water
• In DM glucose cant cross
• GLUT 1 is a receptor for glucose in Red blood cells (RBC)
• GLUT 4 in adipose tissue and muscle
• Effecitve osmole for the vascular compartment: Albumbin

5. OSMOSIS

6. EXTRACELLULAR SOLUTES
• Na+: 140
• K+: 4
• Cl: 104
• HCO3- : 24
• Measured in mEq/L; mmol/L; mM
BUN: 15
Cr: 1
Glucose: 80
Measured in mg/dl and mg%

7. Osmolar GAP
• 𝐸𝑠𝑡𝑖𝑚𝑎𝑡𝑒𝑑 𝑜𝑠𝑚𝑜𝑙𝑎𝑙𝑖𝑡𝑦 = 2 𝑁𝑎 + +
𝐺𝑙𝑢𝑐𝑜𝑠𝑒
18
+
𝐵𝑈𝑁
2.8
• 𝐸𝑠𝑡𝑖𝑚𝑎𝑡𝑒𝑑 𝑜𝑠𝑚𝑜𝑙𝑎𝑙𝑖𝑡𝑦 = 2 𝑁𝑎 + +
𝐺𝑙𝑢𝑐𝑜𝑠𝑒
20
+
15
3
• 𝐸𝑠𝑡𝑖𝑚𝑎𝑡𝑒𝑑 𝑜𝑠𝑚𝑜𝑙𝑎𝑙𝑖𝑡𝑦 = 2 140 + +
80
20
+
30
3
• Estimated osmolality: 280 + 4 + 5= 289

8. OSMOLAR GAP
• Osmolar Gap: Difference in stimated and measured osmolarity.
Measure should be more than 15 above stimated
• Result of Clinical vignette
• 𝐸𝑠𝑡𝑖𝑚𝑎𝑡𝑒𝑑 𝑜𝑠𝑚𝑜𝑙𝑎𝑙𝑖𝑡𝑦 = 2 150 +
100
20
+
30
3
= 315
Plasma osmolarity of paciente: 320
Osmolarity measured of the paciente: 315
• Osmolar gap: 320 – 315 = 15

9. Darrow – Yannet Diagram
•Excersice are in the book (pag 8)
•Two big player for volumen regulation are:
•Aldosterone
•Anti-Diuretic Hormone (ADH; also called AVP

10. • Primary factors regulating Renin
1. Perfusion pressure to the kidney (PP)
2. Sympathetic stimulation (Beta-1 receptor) – Renin ↑
3. Na+ delivery to the macula densa (Nephron)
• Primary factors regulating Aldostenore
1. Plasma (angiotensin II) stimulates release (RAAS)
NEGATIVE FEEDBACK SYSTEM
2. Plasma K+ stimulates release
• Primary factors regulating ADH (AVP)
1. Plasma osmolarity stimulates
2. Blood volumen/pressure (inversely related)
RAAS
↓PP – Renin ↑
↑PP – Renin ↓
↓[𝑵𝒂+] – Renin ↑
↑[𝑵𝒂+] – Renin ↓
↑Oms - ↑ AVP
↓Oms - ↓ AVP
↓BD ↔ ↑AVP
↑BD ↔ ↓AVP

11. Examples
Volumen Distribution Regulation Clinical
↓ ECF BP ↓ Loss of hypotonic fluid
Dehydration
Sweating and respiration)
Hypotonic urine (diabetes insípida)
↓ ADH could be cause
↓ ICF RAAS ↑
↑ OSM AVP ↑

12. Volumen Distribution Regulation Explaination Clinical
↑ ECF BP ↑
Add more osmole
which stay in
Extracellular
volumen
Excessive salt intake
Hypertonic saline
Hypertonci manitol
Initial effect of hyperglycemia
↓ ICF RAAS ↓
↑ OSM AVP ↑/↓/↔

13. Volumen Distribution Regulation Explaination Clinical
↑ ECF BP ↔
Add more wáter so
it drops osmolarity
Primary polidipsia hypotonic
saline
SIADH
Increased ADH could be the
cause
↑ ICF RAAS ↓
↓ OSM AVP ↓

14. Volumen Distribution Regulation Explaination Clinical
↑ ECF BP ↑
Add more equal solute
(osmole) and water
Infusion of isotonic fluid such as saline (entire ECF
expands)
Infusion of solution with colloids (dextran, plasma
with proteins) expands plasma portion of ECF
Pathology: Increased Aldosterone, Primary
aldosteronism (Conn's síndrome)
No change ICF RAAS ↓
No change OSM AVP ↓

15. Volumen Distribution Regulation Explaination Clinical
↓ ECF BP ↓
Loss more osmoles
Decreased of Aldosterone
Addison's disease
↑ ICF RAAS ↑
↓ OSM AVP ↑/↓/↔

16. FluidFlux
Hydrostatic Pressure (P)
Filtration (+)
𝑃𝑐
Flow
Venous Pressure
Blood Volumen
𝜋𝐼𝐹 Osmotic forces in the intersticial
Osmotic/Oncotic pressure (π)
Absorption (-)
πc
Osmoles = Plasma protein
Any solute that doesnt croos the
membrane is gonna pull wáter
𝑃𝐼𝐹
Hydrostatic pressure in the
interstitial
𝑃𝑐 :Hydrostatic pressure in the capillary
𝜋𝐼𝐹 Oncotic pressure of the instertitial
πc:Oncotic pressure in the capillary
𝑃𝐼𝐹 Hydrostatic pressure in the interstitial

17. Filtration and Absortion – Fluid Flux
Hydrosteatic pressure (P)
• Pc promotes Filtration (+) means
pushing water out also means gradient
1. Hydrostatic pressure in the Capillary
• Regulated by 3 things
1. FLOW (Regulated at arteiole)
2. VENOUS PRESSURE (directly related)
3. BLOOD VOLUMEN (Greater the volumen
greater thepressure
2. Oncotic pressure in the interstitial
Oncotic pressure (π)
• Oncotic promotes Absorption (-)
• Oulling water to the capillary
1. Oncotic pressure in the capillary
• Osmoles in the capillary that pull water
out (Albumin)
2. Hydrostatic pressure in the intertitial

18. STARLING EQUATION • Qf: filtration
• k: filtration coeficiente
• Relates to permeability
• If the capillary is more permeable
increased the filtration
• ↑ permaebility = ↑ Filtration
• Lymphatics: Regulate
• 𝜋𝐼𝐹 Oncotic pressure in the interstitial
• 𝑃𝐼𝐹 (Hydrotastic pressure in the
intertitial)

19. Exercise
• Calculate Net pressure
Pc: 25 mm Hg
PIF: 2 mm Hg
πc: 20 mm Hg
π IF: 1 mm Hg
Calculate Net pressure
(Pc + π IF ) – (πc – PIF)
(25+1) – (20 + 2)
R: 4

20. Primary causes of edema
• Increased Pc:
• Flow: vasodilation
• Venous pressure: Venous obstruction, heart failure
• Blood volumen: (Na+ retention) Heart failure
• Increased π IF : Hypothyroid – Myxedema
• Decreaed vascular oncotic pressure: Liver; Kidney
• Increased Capillary permeability: Inflammatory response (TNF-Alpha;
histamine; bradykinin
• Lymphedema: Filarial (W. Broncofti); bacterial lymphangitis (streptococci);
trauma, surgery, tumor
PITTING EDMA
NO PITTING EDMA

21. CLINICAL VIGNETTE
•If TNF (Tumor necrosis factor) and BK (Bradykinin) are
increased
• Increased permeability
↑ FLOW
↑ PC (Hydrostatic Pressure in the capillary
↑ FILTRATION
Which decreased PTC (precapillary arteriolar tone) and PNE
(Pre-capillary noepinephrine contration/release

22. PULMONARY EDEMA
Most common form of pulmonary edema
• Cardiogenic (elevated PC)
• In this condition the patient is not injecting blood
(Right heart start to fail blood is going to back up)
• Increased left atrial pressure
• Increased venous pressure which in turn increased
capillary pressure
• Initially increased lymph Flow reduces interstitial
proteins and is protective
• First clinical sign is ORTHOPNEA (disnea when
supine), which can be relieved SITTING UPRIGHT
PURMONARY
EDEMA
↑Left atrial
pressure
↑Venous
pressure
↑Capillary
pressure

23. PULMONARY EDEMA
• Non-cardiogenic (increased
permeability)
• Adult respiratory distress síndrome
(ARDS)
• Due to direct injury of the alveolar
epithelium or after a primary injury to
the capillary endothelium
• Clinical signs are severe disnea of
rapid onset, hipoxemia and diffuse
pulmonary inflitrates leading to
respiratory failure
Most common causes
SEPSIS
Most important
Bacterial
pneumonia
Trauma
Gastric
aspitation

24. PULMONARY EDEMA
•Non-cardiogenic
•Fluid accumulation as a result of the loss of epithelial
integrity
•Presence of protein containing fluid in the alveoli
inactivates surfactant causing reduced lung
compliance
•Pulmonary wegde pressure is normal or low

25. VOLUMEN MEASUREMENTS
• INDICATOR-DILUTION
• Volumen of distrinution in
pharmacology
• 𝑉 =
𝐴
𝐶
Properties of Tracer
Introduced into a vascular
compartment and distribute until
they reach a barrier they can’t
penétrate.
• Two major barrier are
• Capillary membrane
• Cell membrane
Plasma: Doesnt cross capillary (e.g
albumin)
ECF: Cross capillary but not the cell
membrane (e.g., mannitor, sodium,
sucrose)
Total body water: Permeable to
capillary and cell membrane (water
and urea)

26. Volume measurement of compartments
• Blood volumen: RBC volumen + plasma
• Blood volumen =
𝑃𝑙𝑎𝑠𝑚𝑎 𝑉𝑜𝑙𝑢𝑚𝑒
1 −𝐻𝑒𝑚𝑎𝑡𝑜𝑐𝑟𝑖𝑡
Example
Ht:50mg (0.50)
Plasma volumen = 3L
𝐵𝑙𝑜𝑜𝑑 𝑉𝑜𝑙𝑢𝑚𝑒𝑛 =
3𝐿
1 − 0.5
= 6𝐿