Exam 4 Flashcards
Excess NaCl intake
Avg 2-3x more than what we need
Too much increases plasma osmolarity and causes cells to shrink
Handled via mass balance
2 part response to salt intake
Cardiovascular (fast)
Renal (slow)
Vasopressin and thirst response change ECF volume, BP, & osmolarity
Reabsorption vs. secretion regulation
ONLY regulate reabsorption
Can’t increase secretion of salt
Aldosterone
Steroid hormone from adrenal cortex
Increases Na reabsorption and K secretion in distal nephron
Slow Aldosterone response
Production of new channels via transcription/translation
Fast aldosterone response
Increase activity of the channels present
Ion transporters targeted by aldosterone
Na/K pump
ENaC (Epithelial Na Channel)
ROMK (Renal Outer Medulla K channel)
SEE DIAGRAM Slide 31
Primary stimuli for aldosterone release
Increased Extracellular K+ (detected by adrenal cortex, protection against hyperkalemia)
Low blood pressure (Triggers RAAS)
RAAS
Renin Angiotensin Aldosterone System
GO OVER PATHWAY/DIAGRAM slide 34
6 possible effects of ANG II
Constrict arterioles
CVCC (SNS) to increase Cardiac response
Hypothalamus to increase vasopressin and thirst
Adrenal cortex to release aldosterone
Proximal tubule to increase Na reabsorption
All lead to increased BP and/or Increased volume and maintained osmolarity
ACE-inhibitors
Lower BP by preventing conversion of ANG I to ANG II
Increases vasodilation
Angiotensin receptor blockers (ARB)
Competitive binding of AT1 receptors prevents intracellular response to ANG II
Renin Inhibitors
Reduce Renin activity
Can’t be used in combo with other RAAS drugs
Natriuresis
Losing sodium in urine
Natriuretic peptides
Oppose RAAS system
Decrease BP
Atrial natriuretic Peptide (ANP)
Produced in cardiac atria
Myocardial stretch (Increase BP) triggers release
Enhances Na and water excretion, multiple effects
Brain Natriuretic peptide (BNP)
Produced in some neurons and ventricular myocardium
Marker to estimate heart failure
Hypokalemia
Low IF K+
Increases K+ gradient
Resting membrane potential becomes more negative, so harder to excite cells
Muscle weakness, feeling tired
Hyperkalemia
Excess IF K+
Decreases gradient
Resting membrane potential becomes less negative so it’s easier to fire AP
Cardiac arrythmias, fast HR
Less excitable over time
Common disturbances of K+ levels
Kidney disease, ED, K+ loss in diarrhea, certain diuretics
What response when K+ too high
Aldosterone increase K+ excretion via increase activity/expression of Na/K pump
Thirst reflex
Osmoreceptors in hypothalamus
Receptors in mouth/pharynx respond to cold water to reduce thirst and vasopressin
Salt appetite
Crave salt when Na lost; linked to aldosterone and angiotensin
Hypothalamic response - osmoreceptors monitor plasma
Fluid loss
Excess sweating, vomit, diarrhea, hemorrhage
Fluid gain
Excess water consumption dilutes ECF; hyponatremia, hypokalemia
Amateur athletes over hydration
Severe dehydration
5-10% water loss, goal is to restore BP, ECF volume, and osmolarity
Lose way more H2O than ions in sweat
3 Major mechanisms to oppose dehydration
- Conserve fluid and prevent further loss
- Trigger CV to increase BP
- Stimulate thirst to establish normal volume and osmolarity
4 systems involved to respond to dehydration
CV
RAAS
Renal
Hypothalamic
GO OVER FLOW CHART SLIDE 49
pH
Measure of H+ concentration
7.38-7.42 in the body
Change in 1 log unit is a 10 fold difference in ion s
Why is pH homeostasis critical for life
Acidic pH denatures proteins
Acidosis reduces neuron excitability and depresses ventilation
Alkalosis enhances neurons excitability
Primary sources of acid
Diet and metabolism
Primary elimination of acid
Ventilation and Renal
Three main mechanisms to cope with pH change
Chemical buggers (1st line of defense)
Ventilation (2nd line of defense)
Renal (last line, slower, control excretion/reabsorption of H+ and HCO3-)
Chemical buffer Mechanism
Buffer moderates but does not prevent pH change (temporary)
Most combine with H+
Intracellular buffers
Proteins
Phosphate ions (HPO42-)
Hemoglobin
Extracellular buffers
Bicarbonate
600,000x more concentrated than H+
Ventilation buffer mechanisms
Respiratory compensation (increase CO2 production increases ventilation)
Nearly instant response
Hypoventilation
Decrease rate and depth
Increases CO2
More acidic so increase vent to overcome
Hyperventilation
Decreases CO2
More basic pH so decrease ventilation
Renal buffer mechanisms
Alters pH directly by excreting or reabsorbing H+ OR indirectly by changing the rate that HCO3- is excreted or reabsorbed
Apical Na+H+ exchanger
NHE
Active transporter brings Na+ into cell to move H+ against its gradient
Basolateral Na+-HCO3- symporter
Moves Na+ and HCO3- out of epithelial cell into interstitial fluid
H+K+ ATPase
Moves H+ into urine in exchange for reabsorbed K+
Can lead to K+ imbalance
Na+NH4+ antiporter
Moves NH4+ from cell to nephron lumen in exchange for Na+
Bicarbonate Reabsorption
Filter 1lb of HCO3- per day
PT reabsorbs by converting it into CO2 then back into HCO3-
OR metabolism of glutamine which leads to net reabsorption of Na+ and HCO3- (by product of glut. metab)
Bicarb reabsorption Diagram
Go over diagram
Draw it out
Know transporters
Acid Excretion
Distal nephron
Intercalated cells contain CA
Type A and Type B cells
Type A cells
Intercalated cells secrete H+ and reabsorb HCO3-
Used in acidosis
Type B Cells
Intercalated cells that secrete HCO3- and reabsorb H+
Used in Alkalosis
Intercalated Cells Acid base balance
DIAGRAM
Transporters
Acid base disturbances categorized by 2 things
Direction of pH change (Acidosis/alkalosis)
Source of disturbance (metabolic or respiratory)
Respiratory Acidosis
Hypoventilation and CO2 retention
Elevates PCO2
Decreased pH with elevated HCO3-
Renal compensation is the only method (Type A cells)
Causes of Respiratory acidosis
Drugs that depress ventilation
Increased airway resistance
Impaired gas exchange
Muscle weakness
COPD
Metabolic acidosis
H+ input exceeds excretion
Lactic acid production (lactic acidosis)
Ketone production (Ketoacidosis)
Loss of HCO3- due to diarrhea
Ventilation and renal compensation (type A)
Respiratory alkalois
Results from hyperventilation (too much CO2 exhaled)
Alveolar ventilation increases but not metabolic CO2 production
Only compensation is renal HCO3- secretion (Type B) and H+ reabsorption
Metabolic alkalosis
Excessive vomiting of stomach acid or excessive ingestion of bicarbonate
Reduces H+ and increases HCO3-
Plasma CO2 decrease
Ventilation (Hypovent to retain CO2) and renal compensation (Type B, secrete HCO3- reabsorb H+)
Challenges exercise presents to homeostasis
Increase BP, vent, temp, HR, ATP demand, water loss
Decrease pH (More acidic)
Systems integrated in exercise response
CV, renal, respiratory, nervous
Energy forms in skeletal muscle
ATP stores
Phosphocreatine (PCr)
Phosphocreatine (PCr)
Transfers phosphates to ADP to make ATP via creatine Kinase
Only provides energy for ~15s of intense contraction (sprinting, weightlifting)
Pathway of energy for muscles
Recreate diagram!
3 main pathways: Anaerobic (glycolyis, lactase), Aerobic (CAC, ETC), PCr
Where does glucose come from
Liver glycogen or dietary intake
Where can fatty acids be used
Only in aerobic metabolism
Anaerobic metabolism
No need for O2
Advantage is speed of ATP production
Disadvantage is quantity of ATP ~2 and contributes to metabolic acidosis via lactic acid
Aerobic metabolism
Uses O2
Advantage is high yield ~32 ATP
Disadvantage is generation of ATP is much slower
Much longer sustained contraction
What process produces ATP fastest
PCr
But lowest muscle endurance
Fat glucose usage in exercise
At lower intensities, fat is primarily used but as intensity increases glucose takes over
See graph
Oxygen consumption (VO2)
O2 combines with H to make H2O in mitochondria
Determines intensity (L/min)
VO2 Max
Indicator of ability to perform endurance exercises
Greater number = greater ability to do work
Why does ventilation increase so quickly when exercise begins
Anticipation of oxygen demand (feedforward control)
Stretch receptors in muscles trigger increase in vent.
How come PO2 and PCo2 stay constant during exercise
Exercise hyperventilation keep them equal
Cardiovascular response to exercise
Mechano-sensory info from muscles –> motor cortex
Descending pathways activate CVCC –> sympathetic output increases CO and constrict most peripheral arterioles
Prime factor of exercise tolerance
O2 delivery
CO = HR* SV
Blood flow during exercise
Vasoconstriction of non exercising tissue and dilation of exercising tissue pushes blood to muscles
Why does the BP increase during exercise not trigger homeostatic compensation
Motor cortex signals “reset” baroreceptor threshold
Baroreceptors afferents are blocked (central inhibition)
Sensory input (H+) and muscle mechanoreceptors override the baroreceptors
What causes activation of CVCC at the onset of exercise
Muscle mechanoreceptors
