Unit 2 Pathophysiology - Chapter 3 The Cellular Environment Flashcards
Does ICF (Intracellular fluid) have most body water weight?
distribution of body fluids
Yes @ 40%
Total body water (TBW) for newborn infant
distribution of body fluids
70-80% d/t less fats stored
Total body water in childhood
distribution of body fluids
60-65%
Total body water in adults
distribution of body fluids
50-60%
What are the four forces hat determine if fluid moves out of the capillary to interstitial space? (as plasma flow from arteries to venous end of the capillary)
- capillary hydrostatic pressure (blood pressure)
- capillary (plasma) oncoctic pressure
- interstitial hydrostatic pressure
- interstitial oncotic pressure
distribution of body fluids
What is the overall movement between capillaries, interstitial, and lympathtic system?
distribution of body fluids
capillaries
a) aterial end - capillary hydrostatic pressure greater than capillary oncotic forces means water goes into interstitial (some water pulled into capillary d/t oncotic forces)
b) loss of water decreases capillary hydrostatic pressure at venous end; causing fluids to be attracted back into circulation
AS A RESULT => filtration (Arterial end) => reabsorption at venous end
interstitial hydrostatic/oncotic pressure + intracellular osmotic pressure (move to cells + lympathic)
Edema - increased capillary hydrostatic pressure
Alterations in Water Movement
Venous obstruction, or sodium and water retention.
- usually behind obstruction
- Rt congestive heart failure, renal failure, cirrhosis => water and sodium retention
Edema - decreaed capillary oncotic pressure
Alterations in Water Movement
results from losses or diminished production of plasma albumin => fluid moves out from capillary => d/t decreased synthesis of plasma protein, liver disease, protein malnutrition, glomerular diseases of the kidney, hemorrhage, serous drainage from open wounds or burns
Edema - increased capillary permeability
Alterations in Water Movement
inflammation and immune response; trauma, burns, crush injuries, neoplastic disease, allergic reactions, infection // more proteins enter interstitial space increasing interstitial oncotic pressure drawing even mroe water! => edema gang
edema - Lymphatic obstuction
Alterations in Water Movement
infection or tumor; protein and fluids are not reasorbed and accumulate in interstitial space // can happen after surgical removal of axillary or femoral lymph nodes (cancer tx)
In general pathophysiologic process that leads to edema favors what?
Alterations in Water Movement
fluid filtration from capillaries to tissues
Edema sx
Alterations in Water Movement
swelling, puffiness, tighter-fitting clothes, limited movement, weight gain
Sodium important for what other “functions”?
Sodium, Chloride, and Water Balance
neuromuscular irritability for conduction of nerve impulses (conjunction w/ potassium and calcium). regulates acid-base balance (na+ bicarb / phosphate), cellular chemical reactions, transport of substasnce across membrane
Daily intake of sodium?
Sodium, Chloride, and Water Balance
500 mg
Aldosterone
Sodium, Chloride, and Water Balance
Kidney secrete renin (when renal blood flow and blood pressure, or Na+ are low) =>
angiotensinogen (liver) => react with renin (to form angiotensin 1)
angiotensin I (converted in pulmonary vessels) => to angiotensin II via ace (released from lungs)
angiotensin II causes elevated systemic blood pressure and secretion of aldosterone (mineralcorticoid, adrenal cortex as end product of renin-angiotensin-aldosterone system) =>
aldosterone promotes sodium and water reabosrption by proximal tubules while secreting potassium (end result: conserve Na+, increase blood volume and pressure)
Natriuretic hormone (ANP or BNP)
Sodium, Chloride, and Water Balance
During incresaed transmural atrial pressure d/t incresaed intraatrial volume (possibly heart failure) => ANP and BNP inc sodium and h2o excretion by kidnyes, which lowers blood volume and pressure
antagonist to renin-angiotensin-aldosterone system
remeber natriuretic (prevents reabsorption of Na+ from urine)
Urodilatin
Sodium, Chloride, and Water Balance
released from distal tubular kidney cells when there is increased arterial pressure and increased renal blood flow. Decrease sodium reabsoption
It inhibits salt and water reabsorption.
Urodilatin (a natriuretic peptide) inhibits sodium and water reabsorption from the medullary part of collecting duct, thereby producing diuresis.
Antidiuretic hormone (ADH)
Sodium, Chloride, and Water Balance
Also called vasopressin, plasma osmolality high, blood volume low, or blood pressure drops => produce less urine, constrict vessels, reabsorb more water
Isotonic
Alterations in Sodium, Water, and Chloride Balance
changes in total body water accompanied by proportional changes in concentrations of electrolytes
Hypertonic
Alterations in Sodium, Water, and Chloride Balance
osmolality of ECF is elevated above normal, d/t increased Na+ or lack of water (cell would shrink)
Hypotonic
Alterations in Sodium, Water, and Chloride Balance
osmolality lower than normal; water gain or solute loss (cells swell)
Euvolemic hypernatremia
Alterations in Sodium, Water, and Chloride Balance
Hypernatremia with euvolemia is a decrease (normal or minimal) in TBW with near-normal total body sodium (pure water deficit).
Loss of free water with near normal body sodium concentration; poor water intakae, excessive sweating, fever, water loss from lungs, burns, vomiting, diarrhea, diabetes insipidus (A disorder of salt and water metabolism marked by intense thirst and heavy urination)
Dehydration
Alterations in Sodium, Water, and Chloride Balance
Water loss + sodium loss
Hypervolemic hypernatremia
Increased total body water, greater Na+ concentration; hypertonic solution (w/ renal impairment, heart failure, GI loss), oversecretion ACTH or aldosterone (cushing, adrenal hyperplasia), near salt water drowning
hypercholremia
Alterations in Sodium, Water, and Chloride Balance
often accompanies hypernatremia + plasma bicarbonate deficits (hyperchloremic metabolic acidosis)
metabolic acidosis characterized by a decrease in serum pH and serum bicarbonate [HCO3–] with a matched rise in serum chloride level (due to retention of chloride in the serum) which maintains a normal anion gap
Hypernatremia sx
Alterations in Sodium, Water, and Chloride Balance
weakness, lethargy, muscle twitching, hyperrflexia, confusion, coma, seizures (d/t shinking of brain cells)
What can hyponatremia cause?
Alterations in Sodium, Water, and Chloride Balance
Cause water to enter cells!
Potassium
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
Regular ICF osmolality, maintain resting membrane potential, deposit glycogen in liver + skeletal muscle cells
Euvolemic hyponatremia
Alterations in Sodium, Water, and Chloride Balance
total body water increases, but the body’s sodium content stays the same
Caused by SIADH (antidiuretic) - water retention, hypothyroidism (decreased cardiac output), pneumonia (hypercapnia), glucosteroid deficiency (retain less na+)
Syndrome of inappropriate antidiuretic hormone (inc water reabsorption in distal nephron producing a conc urine and diluted plasma)
Hypervolemic hyponatremia
Alterations in Sodium, Water, and Chloride Balance
TBW and Na+ elevated; but sodium is lesser => hypotonic hyponatremia
Hypotonic hyponatremia represents an excess of free water. This excess free water can be caused by two mechanisms:
Increased free water intake: The patient drinks a large volume of free water (greater than 18 L/day or greater than 750 mL/h) that overwhelms the kidney's capacity to excrete free water. Examples of this are psychogenic polydipsia, marathon runners, water drinking competitions, and ecstasy. Decreased free water excretion: Patients drink a normal volume of free water, but the kidneys cannot excrete the water for some reason.
- High ADH activity: Three different mechanisms can cause high ADH:Decreased effective arterial blood volume (EABV): antidiuretic hormone (ADH) is released when there is a reduction of 15% or more of the EABV. This occurs with hypovolemia (e.g., vomiting, diarrhea), decreased cardiac output (e.g., heart failure), or vasodilation (e.g., cirrhosis).SIADH: ADH is secreted autonomously. Four general causes of this are brain disorders, lung disorders, drugs (e.g., SSRI), and miscellanea (e.g., nausea and pain).Cortisol deficiency: Cortisol exerts an inhibitory effect on ADH release. When cortisol is decreased, ADH is released in large amounts. Adrenal insufficiency is the cause of this mechanism.[12]
- Low glomerular filtration rate
- Low sodium intake
Hypertonic hyponatremia
Alterations in Sodium, Water, and Chloride Balance
shift water ICF => ECF w/ hyperglycemia, hyperlipidemia, and hyperproteinemia; diluting sodium and other electrolytes
What does increased serum K+ level stimulate?
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
Regulation via Insulin, aldosterone (renal excretion), and epinephrine (beta-adrenergic) secretion as well as activating K+ transport into liver and muscle cells (As for epinephrine and its effect on potassium, it is well known that epinephrine causes hypokalemia [5, 6]. This results from epinephrine-induced stimulation of b2 re- ceptors present in skeletal muscle that causes an intra- cellular shift of potassium.)
(simulatenously with glucose transport w/ insulin use, risk of low plasma k+ w/ Na+-K+ pump if administering insulin w/ low intrinsic k+)
What causes K+ to shift out of cell?
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
Insulin deficiency, aldosterone deficiency, acidosis (A frequently cited mechanism for these findings is that acidosis causes potassium to move from cells to extracellular fluid (plasma) in exchange for hydrogen ions, and alkalosis causes the reverse movement of potassium and hydrogen ions), strenuous exercise (A progressive hyperkalemia is observed as exercise intensity increases. The current most popular hypothesis for the hyperkalemia is that the Na+-K+ pump cannot keep pace with the K+ efflux from muscle during the depolarization-repolarization process of the sarcolemmal membrane during muscle contraction.)
What does alpha-adrenergics and glucagon do to K+?
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
impair K+ entry into cells
Alpha 2 prevents insulin release (meaning more glucose in serum)
Thus, glucagon is similar to epinephrine in that it elevates blood potassium and glucose and dissimilar in that it has no cardiovascular effects.
A significant rise in serum potassium may result from a sudden increase in plasma osmolality which shifts water out of the cell and drags in some potassium with the water (d/t inc glucose)
Glucagon is a hormone that is involved in controlling blood sugar (glucose) levels. It is produced by the alpha cells, found in the islets of Langerhans, in the pancreas, from where it is released into the bloodstream. The glucagon-secreting alpha cells surround the insulin-secreting beta cells, which reflects the close relationship between the two hormones.
Glucagon’s role in the body is to prevent blood glucose levels dropping too low. To do this, it acts on the liver in several ways:
It stimulates the conversion of stored glycogen (stored in the liver) to glucose, which can be released into the bloodstream. This process is called glycogenolysis. It promotes the production of glucose from amino acid molecules. This process is called gluconeogenesis. It reduces glucose consumption by the liver so that as much glucose as possible can be secreted into the bloodstream to maintain blood glucose levels.
Glucocoritioids promote what w/ potassium?
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
Potassium secretion
Alkalosis and acidosis for k+ bx
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
Alkalosis (K+ shift into cells; H+ outside cells) and acidiosis (K+ shift outside cells; while H+ enters cells)
Prinicipal cells (collecting duct)
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
mediates the collecting duct’s influence on sodium and potassium balance via sodium channels and potassium channels located on the cell’s apical membrane (free surface that is exposed to the luminal fluid.). Aldosterone determines expression of sodium channels (secrete K+)
Principal cells are the main Na+ reabsorbing cells and the site of action of aldosterone, K+-sparing diuretics, and spironolactone.
intercalated cells in collecting dcut
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
reabsorb K+
Hyperkalemic acidosis
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
Due to acidosis in environment, K+ leaves cell causing decreased ICF K+ in distal tubules causing less urine secretion of K+ contributing to hyperkalemia overall.
Hypokalemic alkalosis
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
Due to alkalosis in surrounding, k+ shift into cells for H+ causing increased ICF k+ makes distal tubules secrete more K+ via urine, l/t ultimately hypokalemia.
Potassium adaptation
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
ability of the body to adapt to increased levels of K+ intake over time
Hypokalemia only
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
when K+ <3.5 meq/l // loss of total body K+, ECF hypokalemia may occur w/ no losses in total body potassium while plasma K+ may be normal or elevated when total body K+ is depleted
What causes hypokalemia (5)? and sx?
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
- reduced K+ intake
- inc ECF => ICF K+ concentration
- loss of K+ from body stores (muscle, skin, subq, RBC?)
- increased aldosterone secretion
- increased renal excretion
sx
* neuromuscular excitability
* skeletal muscle weakness (legs + arms => diaphragm)
* paralysis and respiratory arrest
* GI manifestations: constipation, anorexia, n/v, paralytic ileus, intestinal distention
What causes hyperkalemia and sx
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
K+ >5 ;
* caused by increased K+ intake
* shift from ICF => ECF K+
* decreased renal excretion
sx
- dysrhythmias
for mild sx:
* neuromuscular irritability (lips, fingers) + early (hyperactive muscles + reflexes)
* restlessness
* intestinal cramp
for severe sx:
* muscle weakness
* loss muscle tone
* paralysis
Importance of calcium?
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
- bones and teeth structure
- blood clotting (enzymatic cofactor)
- hormone secretion
- fx of cell receptors
- membrane stability (permeabilty and repair)
- transmission of nerve impulses
- contraction of muscles
Phosphate
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
Buffer in acid-base regulation and provides energy for muscle contraction
Parathyroid? And how does it manage ca++ and phosphate?
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
- PTH stimulates reabsorption of ca++ along distal tubule of nephron (hypocalcemia); including excretion of phosphate, bone resorption predominates when continuous exposure to high levels of PTH ensues; promotes calcium and phos- phate absorption in the intestine.
- Hypercalcemia (reverse of above processes) - for phosphase less excretion
How does vitamin D get activated?
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
- Liver - metabolize vitamin?
- serum Ca+ decreases
- stimulates PTH secretion
- Ca++ reabsorbed / phosphate released
- Combination of low initial Ca++ plus increased PTH secretion causes renal activation of Vitamin D
- Vitamin D circulates as a hormone throughout plasma and acts to increase absorption of calcium and phosphate in small intestin, enchance bone calcification, and inrease further renal tubular absorption of calcium + excretion of phosphate
What happens with vitamin D if there is renal failure present?
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
Vitamin D is not activated - also calcium levels drop and phosphate increases
Calcitonin (produced by C cells of the thyroid gland)
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
Decreases calcium levels by inhibiting osteoclastic activity in bone
Acidosis and calcium levels?
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
State of acidosis, ionized calcium increase
Alkalosis and calcium
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
ionized calcium level decreases; protein-bound calcium increases
Hypocalcemia and manifestations
<9 mg/dl ;; inadequate intestinal absorption, deposition of ionized calcium in bone or soft tissue, blood administration (Calcium levels can be significantly decreased with rapidly transfused blood products due to the citrate preservative that is added. Citrate binds to the patient’s endogenous calcium when blood products are administered, rendering calcium inactive. As a result, undesirable physiological effects can occur.) or decreased PTH and vitamin D levels
- inc neuromuscular excitability
- muscle spasms (hands, feet, facial muscles)
- tingling
- osteoporosis
- fractures
- convulsions + tetany
- prolonged QT interval
- cardiac arrest
- bowel sounds
Hypercalcemia
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
> 10.5 mg/dl ;; hyperparathyroidism, bone metastases, sarcodosis (granulomas, small clumps of inflammatory cells), and excess vitamin D
- fatigue
- weakness
- lethargy
- constipation
- impaired renal fx / kidney stones
- dysrhythmias
- bradycardia
- cardiac arrest
- bone pain
- osteoporosis, fractures
Hypophosphatemia
Alterations in Potassium, Calcium, Phosphate, and Magnesium Balance
<2.0 mg/dl ; caused by intestinal malabsorption and increased renal excretion of phosphate
- reduced o2 transport and disturbed energy metabolism
- leukocyte and platelet dysfuction
- Abnormal nerve and muscle fx
- severe cases: irritability, confusion, numbness, coma, convulsions, resp. failure (muscle weakness), cardiomyopathies, bone resorption
Hyperphosphatemia
> 4.7 mg/dl ; develops with acute or chronic renal failure with significant loss of glomerular fx
- low serum ca++ levels
- similar sx to hypocalcemia
- inc neuromuscular excitability
- muscle spasms (hands, feet, facial muscles)
- tingling
- osteoporosis
- fractures
- convulsions + tetany
- prolonged QT interval
- cardiac arrest
- bowel sounds
Magnesium
major intracelluar cation (regulated by PTH; when released => increases mg+ => magnesium reabsorption in the renal tubule, absorption in the gut and release of the ion from bone); metabolism balanced by kidney and small intestine
important in:
* protein synthesis
* nucelic acid stability
* neuromuscular excitability
* calcium interaction, vitamin D metabolism, parathyroid fx
The body depends on magnesium to convert Vitamin D into its active form within the body. Magnesium also helps Vitamin D bind to its target proteins, as well as helping the liver and the kidneys to metabolize Vitamin D.
Hypomagnesemia and sx
caused by malabsorption syndromes // <1.5 meq/l
sx:
* bh changes (irritability)
* increased reflex + muscle cramps
* ataxia (poor coordination)
* nystagmus
* tetany/convulsions
* tachycardia
* hypotension
Hypermagnesemia and sx
> 3.0 meq/l // rare and caused by renal failure
sx:
* Lethargy, drowsiness
* loss DTR
* n/v
* muscle weakness
* hypotension
* bradycardia
* heart block
* cardiac arrest
ph less than 7.4 and ph greater than 7.4
Acid-Base Balance
acididc // basic
Which major organs are invovled in acid-base regulation?
Acid-Base Balance
Lungs, kidneys, bone
Body acids: volatile and nonvolatile
Acid-Base Balance
Volatile
* respiratory acids - eliminated as CO2 gas
Nonvolatile
* metabolic acids - eliminated by kidney or metabolized by the liver
* carbonic acid H2CO3; formed by hydration of carbon dioxide
Regulated by lung //// Regulated by kidney
CO2 + H2O .. H2CO3 …..HCO3- + H+
Carbonic anhydrase readily dissociates carbonic acid (weak acid) into CO2 and H2O (therefore volatile)
Examples of nonvolatile strong acids?
Acid-Base Balance
sulfuric, phosphoric, other metabolic acids (lactic acid, pyruvic acid, and keto acids [acetoacetic acid, b-hydroxybutyric acid, related to DM[) produced from incomplete metabolism of proteins, carbohydrates, and fats
Buffers
Acid-Base Balance
absorb excessive H+ (acid) or hydroxyl ion (OH- or Base) to minimize fluctuations in pH.
These systems exit in ICF and ECF compartments; usually as pairs consisting of weak acid and its conjugate base
MOST IMPORTANT ones:
Plasma buffer systems:
bicarbonate-carbonic acid + hemoglobin
H2CO3 (carbonic) + HCO3- (bicarb) (H+ + HCO3- <=> H2O + CO2 ) ///// HHb ⇄ H+ + Hb−
Intracellular buffers
phosphate + protein (1st line of defense)
HPO4- + H <-> H2PO4- // HPr ⇄ H+ + Pr
Renal buffers
Ammonia and phosphate (can attach hydrogen ion)
Lungs - buffer system
Acid-Base Balance
Regulates retention or elimination of CO2 and importantly H2CO3 (bicarbonate)
Ionic shifts - buffer system
Acid-Base Balance
K+ intracellular and hydrogen
Kidneys - buffer system
Acid-Base Balance
Bicarbonate reabsorption and regeneration, ammonia formation (Intestinal bacteria decompose protein into ammonia by producing urease. Intestinal ammonia can be absorbed into the bloodstream. After ammonia is transported into the portal vein, it enters the liver and is re-synthesized to urea => secreted via kidneys), phosphate buffering (The phosphate buffer system is almost identical to the bicarbonate buffer system—where phosphates work—in the intracellular fluid.)
Nonvolatile acids are eliminated by (lactic acid, phosphoric acid, sulfuric acid, acetoacetic acid, and beta-hydroxybutyric acid. )
Bone - buffer system
Acid-Base Balance
Increased osteoclastic bone resorption releases alkali as well as mineral from bone. Thus, bone serves as a buffer and in the process of neutralizing acid arising from acid-producing diets, net bone loss occurs.
An increase in pH, alkalosis, promotes increased protein binding, which decreases free calcium levels. Acidosis, on the other hand, decreases protein binding, resulting in increased free calcium levels.
What systems utilize the carbonic acid-bicarbonate buffering?
Acid-Base Balance
Kidney and lung
Acid-base imbalances + compensations
Acid-Base Balance
- Is pH high or low? If low acidemia, if high alkalemia
- Once determined, is the cause respiratory or metabolic
- Is there compensation for either?
Pa CO2 (acid) (alkalosis < 38 == 40 == 44 mmHg < acidosis ) === > respiratory
HCO3- (base) (acidosis < 22 == 24 === 26 meq/l < alkalosis ) ===> metabolic
Resiratory acidosis ( > 44 mmHg paCO2) ==> renal bicarbonate retention and hydrogen elimination (HCO3- > 24)
Respiratory alkalosis (< 38 mmHg paCO2) ===> renal bicarbonate elimination and hydrogen retention (HCO3- < 24)
Metabolic acidosis (< 22 meq/l HCO3-) ===> respiratory co2 elimination (hyperventilation) [< 40 mmHg PaCO2]
Metabolic aklalosis (> 26 meq/l HCO3-) ====> respiratory co2 elimination (hypoventilation) [> 40 mmgHg PaCO2]
Metabolic acidosis
Acid-Base Balance
an increase in non-carbonic acis or loss of bicarbonate from extracellular fluid
Metabolic alkalosis
Acid-Base Balance
Increase in bicarbonate conc. usually d/t loss of metabolic acids from vomiting, GI suctioning, excessive bicarbonate intake, hyperaldosteronism (secretion of K+/H+, retains Na+), diuretic therapy
Respiratory acidosis
Acid-Base Balance
decreased alveolar ventilation and increase in co2 or hypercapnia
Respiratory alkalosis
Acid-Base Balance
alveolar hyperventilation and dec carbon dioxide concentration, hypocapnia
