PHYSIOLOGY

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 capillarymembrane• ISF: Interstitial FLUID

• Vascular Volumen: Proteins (Albumin cant cross the capillary membrane

OSMOSIS• mOsm/kg: concentration of particles per Kg of solvent

• Osmolarity = Osmolality

• Glucose effective osmole

• Effective osmole: Solute which cant cross the membrane is effectivecausing 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

OSMOSIS

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%

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

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

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

• 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

ExamplesVolumen Distribution Regulation Clinical

↓ ECF BP ↓ Loss of hypotonic fluidDehydrationSweating and respiration)Hypotonic urine (diabetes insípida)↓ ADH could be cause

↓ ICF RAAS ↑

↑ OSM AVP ↑

Volumen Distribution Regulation Explaination Clinical

↑ ECF BP ↑Add more osmolewhich stay in Extracellularvolumen

Excessive salt intakeHypertonic salineHypertonci manitolInitial effect of hyperglycemia

↓ ICF RAAS ↓

↑ OSM AVP ↑/↓/↔

Volumen Distribution Regulation Explaination Clinical

↑ ECF BP ↔

Add more wáter so it drops osmolarity

Primary polidipsia hypotonicsalineSIADHIncreased ADH could be thecause

↑ ICF RAAS ↓

↓ OSM AVP ↓

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 ECFPathology: Increased Aldosterone, Primaryaldosteronism (Conn's síndrome)

No change ICF RAAS ↓

No change OSM AVP ↓

Volumen Distribution Regulation Explaination Clinical

↓ ECF BP ↓

Loss more osmolesDecreased of AldosteroneAddison's disease

↑ ICF RAAS ↑

↓ OSM AVP ↑/↓/↔

Flu

id F

lux Hydrostatic Pressure (P)

Filtration (+)

𝑃𝑐Flow

Venous Pressure

Blood Volumen

𝜋𝐼𝐹 Osmotic forces in the intersticial

Osmotic/Oncotic pressure (π)

Absorption (-)

πcOsmoles = Plasma protein

Any solute that doesnt croos themembrane is gonna pull wáter

𝑃𝐼𝐹 Hydrostatic pressure in theinterstitial

𝑃𝑐 :Hydrostatic pressure in the capillary𝜋𝐼𝐹 Oncotic pressure of the instertitial

πc:Oncotic pressure in the capillary𝑃𝐼𝐹 Hydrostatic pressure in the interstitial

Filtration and Absortion – Fluid Flux

Hydrosteatic pressure (P)

• Pc promotes Filtration (+) meanspushing 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

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 theintertitial)

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

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

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

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 increasedcapillary pressure

• Initially increased lymph Flow reduces interstitialproteins and is protective

• First clinical sign is ORTHOPNEA (disnea whensupine), which can be relieved SITTING UPRIGHT

PURMONARY EDEMA

↑Left atrial pressure

↑Venouspressure

↑Capillarypressure

PULMONARY EDEMA

• Non-cardiogenic (increasedpermeability)• Adult respiratory distress síndrome

(ARDS)

• Due to direct injury of the alveolar epithelium or after a primary injury tothe capillary endothelium

• Clinical signs are severe disnea ofrapid onset, hipoxemia and diffusepulmonary inflitrates leading torespiratory failure

Most common causes

SEPSIS

Most important

Bacterialpneumonia

Trauma

Gastricaspitation

PULMONARY EDEMA

•Non-cardiogenic•Fluid accumulation as a result of the loss of epithelialintegrity

•Presence of protein containing fluid in the alveoliinactivates surfactant causing reduced lungcompliance

•Pulmonary wegde pressure is normal or low

VOLUMEN MEASUREMENTS

• INDICATOR-DILUTION

• Volumen of distrinution in pharmacology

• 𝑉 =𝐴

𝐶

Properties of Tracer

Introduced into a vascular compartment and distribute untilthey reach a barrier they can’tpenétrate.

• Two major barrier are• Capillary membrane

• Cell membrane

Plasma: Doesnt cross capillary (e.galbumin)

ECF: Cross capillary but not the cellmembrane (e.g., mannitor, sodium, sucrose)

Total body water: Permeable tocapillary and cell membrane (waterand urea)

Volume measurement of compartments• Blood volumen: RBC volumen + plasma

• Blood volumen = 𝑃𝑙𝑎𝑠𝑚𝑎 𝑉𝑜𝑙𝑢𝑚𝑒

1 −𝐻𝑒𝑚𝑎𝑡𝑜𝑐𝑟𝑖𝑡

Example

Ht:50mg (0.50)

Plasma volumen = 3L𝐵𝑙𝑜𝑜𝑑 𝑉𝑜𝑙𝑢𝑚𝑒𝑛 =

3𝐿

1 − 0.5= 6𝐿