What is the concept of balance in the context of body fluid and electrolytes?
Fluid intake (input) = fluid loss (output)
Electrolyte intake (input) = electrolyte loss (output)
What are the four Starling forces?
- Capillary hydrostatic pressure (Pc)
- Interstitial fluid hydrostatic pressure (Pif)
- Plasma osmotic colloid (oncotic) pressure
- Interstitial fluid osmotic colloid (oncotic) pressure
All four forces are the determinants of the net movement of body fluid
What is capillary hydrostatic pressure?
Definition: Pressure of blood pushing against the capillary wall
Effect: Forces fluid out of the capillaries into the interstitial space
Movement: Filtration
May cause edema
What is interstitial fluid hydrostatic pressure?
Definition: Pressure of fluid in the interstitial space pushing against the capillary wall
Effect: Forces fluid into capillaries
Movement: Reabsorption
What is plasma osmotic colloid (oncotic) pressure?
Definition: Pulling pressure created by large proteins, such as albumin, in the blood plasma
Effect: Draws fluid into the capillaries
Movement: Reabsorption
*Clinical connection: Patients with cirrhosis or protein deficiency have hypoalbuminemia, lowering plasma osmotic colloid (oncotic) pressure, which reduces pulling pressure in the capillaries. Thus, fluid is usually in the interstitial space, causing edema.
- Some patients may be given intravenous crystalloid if they are having surgery to maintain blood pressure. Intravenous crystalloid introduces solute into blood plasma. This increases plasma osmotic colloid (oncotic) pressure, drawing fluid into the capillaries, raising blood pressure
What is interstitial fluid osmotic colloid (oncotic) pressure?
Definition: Pulling pressure created by large proteins in interstitial fluid
Effect: Pulls fluid out from capillaries into interstitial space
Movement: Filtration
May cause edema
Which two forces cause filtration when increased?
- Capillary hydrostatic pressure
- Interstitial fluid osmotic colloid (oncotic) pressure
What is the formula for determining the net filtration pressure and movement of fluid?
(Pc — Pif) — (PIp — PIif)
(Capillary hydrostatic pressure — interstitial fluid hydrostatic pressure) — (plasma osmotic colloid pressure — interstitial fluid osmotic colloid pressure)
PI = pi symbol
Positive value = Filtration
Negative value = Reabsorption
What is hyperemia?
Definition: ACTIVE increase in oxygenated blood flow to tissue due to arteriolar dilation, which is regulated by neural, metabolic, and inflammatory signals
Type: Physiologic or pathologic
Physical manifestations: Warmth and erythema (redness)
Examples of physiologic hyperemia: (1) increased blood flow to skeletal muscle during exercise, (2) blushing, and (3) increased blood flow to gastrointestinal tract after a meal
What is congestion?
Definition: PASSIVE accumulation of deoxygenated blood within tissue due to impaired outflow of venous blood
- Venous drainage obstruction either locally (i.e., DVT or venous stasis) or systemically (i.e., heart failure), however, blood flow is continuous via arterioles
- Obstructed venous drainage causes increased engorgement of capillaries, increasing hydrostatic pressure, transudation of fluid into interstitial space, and, thus, edema
- Chronic hypoxia leads to ischemic injury and tissue death
Physical manifestations: Cyanosis (blueness)
What are the two types of edema?
- Intracellular edema (cellular swelling)
- Extracellular (interstitial) edema
What is intracellular edema?
Definition: Abnormal accumulation of fluid within cells, causing cellular swelling
Causes: Hypoxia and ischemia
Pathogenesis:
Hypoxic and ischemic conditions cause cells to switch to anaerobic respiration, producing lactic acid. Lactic acid decreases intracellular pH, damaging intracellular proteins
Anaerobic respiration does not produce very much ATP. When substrates are used up, there is ATP depletion. Since ATP is required for ion pumps, there is an influx of sodium into the cell and an efflux of potassium out of the cell.
Water enters the cell, causing swelling
What is extracellular edema?
Definition: Abnormal accumulation of fluid outside of cells
Causes: Deep vein thrombosis, congestive heart failure, venous stasis, nephrotic syndrome, cirrhosis, malnutrition, inflammation, burns, sepsis, surgery, radiation
Effects:
Increased capillary hydrostatic pressure (DVT, congestive heart failure, venous stasis)
Decreased plasma osmotic colloid (oncotic) pressure (nephrotic syndrome, cirrhosis, and malnutrition)
Increased capillary permeability (inflammation, burns, sepsis)
Decreased lymphatic drainage (surgery and radiation)
Sodium and water retention (renal failure and RAAS activation due to heart failure or cirrhosis*)
*Remember, cirrhosis causes hypoalbuminemia, decreasing plasma osmotic colloid (oncotic) pressure, which causes fluid to leak into interstitial space. If this lowers blood pressure and blood flow to kidneys, RAAS will be activated
What are the types of extracellular edema?
- Peripheral edema (pitting or non-pitting)
- Pulmonary edema
- Periorbital edema
- Scrotal or labial edema
- Unilateral lower extremity edema
What is peripheral edema? What are its types?
Definition: Abnormal accumulation of fluid in the interstitial space of peripheral tissues, most commonly the lower extremities
- Pitting edema
- Non-pitting edema
What is pitting edema? What are its characteristics?
Definition: Type of peripheral edema in which application of pressure with a finger or hand leaves a temporary indentation, or “pit,” in the skin
Causes: Increased capillary hydrostatic pressure (heart failure, deep vein thrombosis, venous stasis), decreased plasma osmotic colloid (oncotic) pressure (nephrotic syndrome, cirrhosis, protein deficiency), chronic kidney disease, certain medications (dihydropyridine calcium channel blockers, such as amlodipine and nifedipine via vasodilation, and thiazide diuretics, NSAIDS)
Characteristics: Normal capillary permeability prevents proteins from leaking into the interstitial space, so fluid in the interstitial space is mostly free water and electrolytes, NOT PROTEINS, making fluid transudate*
*Transudate = transparent (no proteins to cause cloudiness)
What is non-pitting edema? What are its characteristics?
Definition: Type of peripheral edema in which the application of pressure with a finger or hand does NOT leave a temporary indentation, or “pit”
Causes: Decreased lymphatic drainage (removal of lymph nodes or tumor resection) and autoimmune conditions (inflammation, which may be due to Graves’ disease or scleroderma, increases vascular permeability)
Characteristics: Decreased lymphatic drainage and tissue matrix changes (i.e., overproduction of collagen) allow proteins to accumulate in the interstitial space, which tightly bind to water, forming gel-like, non-compressible fluid; PROTEIN-RICH gel makes it exudate
Protein-rich gel/fluid can exacerbate inflammation, leading to deposition of collagen, producing peau d’orange
What is pulmonary edema? What are its characteristics?
Definition: Abnormal accumulation of fluid within the interstitial space of the lungs and alveoli, interfering with normal exchange of oxygen and carbon dioxide
Causes: Heart failure (left ventricle cannot pump effectively, causing blood to back up into pulmonary veins and capillary beds of the lungs, leading increased capillary hydrostatic pressure) and acute respiratory distress syndrome (inflammation causes increased vascular permeability, leading to fluid leakage)
Characteristics (or manifestations): Dyspnea, orthopnea, and pink, frothy sputume
What events occur during normal hemostasis?
- Within seconds, transient reflex arteriolar vasoconstriction reduces blood flow and, thus, blood loss.
- .Within seconds to minutes, primary hemostasis occurs via formation of platelet plug. Endothelial injury exposes sub endothelial collagen and von Willebrand factor. Upon binding to collagen and platelets, it causes platelets to undergo shape change to flat plates with spiky protrusions that release secretory granules containing ADP and thromboxane, which recruit platelets to site of injury, forming primary plug.
- Within minutes, secondary hemostasis occurs via formation of fibrin. Vascular injury also exposes tissue factor, a pro-coagulant GLYCOPROTEIN. Tissue factors binds to CLOTTING FACTOR VII, forming a complex that causes coagulation cascade to form prothrombin. Prothrombin converts to thrombin. Thrombin cleaves fibrinogen to form fibrin, an insoluble protein that forms mesh-like network in blood to form clots and leads to further platelet aggregation.
- Within minutes to hours, clot stabilization via cross-linkage of fibrin by CLOTTING FACTOR VIII and contraction of platelet aggregate to pull edges of wound together.
- Within hours to days, fibrinolysis via tissue-type plasminogen activator, which converts plasminogen to plasmin, an enzyme that degrades fibrin.
What are the counter-regulatory mechanisms of hemostasis?
- Healthy, basal-state endothelium
- Fibrinolysis
- Anti-thrombin III
How does basal-state endothelium counter-regulate hemostasis?
- Shielding platelets from von Willebrande factor and collagen
- Synthesis of nitric oxide, a potent vasodilator that inhibits platelet activation and aggregation
- Synthesis of tissue factor pathway inhibitor, limiting activity of tissue factor
- Basal-state causes thrombin to have anti-coagulant effects via binding to thrombomodulin, a GLYCOPROTEIN expressed on endothelial cells that functions as a cofactor in the conversion of thrombin from a pro-coagulant enzyme into an anti-coagulation one (see below)
Thrombin and thrombomodulin ➡️ thrombin-thrombomodulin complex
Endothelial protein C receptor (EPCR) binds to protein C and presents it to thrombin-thrombomodulin complex ➡️ activated protein C (APC)
Activated protein C and protein S ➡️ inactivation of CLOTTING FACTORS Va and VIIIa shuts down generation of thrombin
What is prothrombin time (PT)?
Definition: An assay (test) that measures time it takes for blood to clot after activation of the EXTRINSIC (initiated by tissue factor) and COMMON (secondary hemostasis and clot stabilization) pathways of coagulation cascade
Procedure: (1) Plasma mixed with tissue factor, artificially triggering extrinsic pathway; (2) timer measures in seconds the time it takes for fibrin clot to form; (3) prothrombin time standardized into internationalized normalized ratio (INR)
What is partial thromboplastin time (activated partial thromboplastin time) (PT/aPTT)?
Definition: An assay that measures the time it takes for blood to clot after activation of the INTRINSIC (does NOT involve tissue factor) and COMMON (secondary hemostasis and clot stabilization) pathways of coagulation cascade
Procedure: (1) Partial thromboplastin, which is phospholipids (stimulates plasma membrane) without tissue factor, and contact activators (negatively charged surface) added to blood sample to artificially trigger intrinsic pathway; (2) timer measures in seconds the time it takes for fibrin clot to form
-
Cell Injury, Cell Death, and Adaptations71
-
The Cell as Unit of Health and Disease134
-
Blood Vessels36
-
Only Tissue Types5
-
Inflammation and Repair1
-
Hemodynamic Disorders28
-
The Immune System19
-
The Heart4
-
Cell Types Of The Anterior Pituitary And Their Hormones6
-
Hyperpituitarism7
-
Hematopoietic And Lymphoid Disorders27
-
The Kidneys24
-
Syndromes Of The Posterior Pituitary5
-
The Adrenal Glands6
-
White Blood Cells, Spleen, and Thymus2
