Typical Concentration Gradients and Membrane Potentials in Excitable Cells

The Na Pump is Particularly Important in the Kidney and Brain

• All cells have Na pumps in their membranes, but some cells have more than others
• Over-all Na pump activity may account for a third of your resting energy expenditure!
• In the kidney the Na pump activity is very high because it is used to regulate body salt and water concentrations
  • Kidneys use enormous amounts of energy: 0.5% of body weight, but use 7% of the oxygen supply
• Pump activity is also high in the brain because Na and K gradients are essential for nerves
  • The brain is another high energy organ; it is 2% of body weight, but uses 18% of the oxygen supply

In the Resting State Potassium Controls the Membrane Potential of Most Cells

• Resting cells have more open K channels than other types
• More K+ passes through membrane than other ions- therefore K+ controls the potential
• Blood K+ must be closely controlled because small changes will produce large changes in the membrane potentials of cells
  • Raising K will make the membrane potential less negative (depolarization)
• High blood K+ can cause the heart to stop beating (it goes into permanent contraction)

During an Action Potential Na Channels Open, and Na Controls the Membrane Potential

• Whichever ion has the most open channels controls the membrane potential
• Excitable cells have Na channels that open when stimulated
• When large numbers of these channels open Na controls the membrane potential

Hypoxia

• Hypoxia is tissue oxygen deficiency
• Brain is the most sensitive tissue to hypoxia: complete lack of oxygen can cause unconsciousness in 15 sec and irreversible damage within 2 min.
• Oxygen delivery and use can be interrupted at several sites

• Causes:
  • Hypoxic: high altitude, pulmonary edema, hypoventilation, emphysema, collapsed lung
  • Anemic: iron deficiency, hemoglobin mutations, carbon monoxide poisoning
  • Ischemic: shock, heart failure, embolism
  • Histotoxic: cyanide poisoning (inhibits mitochondria)

• Carbon monoxide (CO) poisoning:
  • CO binds to the same heme Fe atoms that O₂ binds to
  • CO displaces oxygen from hemoglobin because it has a 200X greater affinity for hemoglobin.
  • Treatment for CO poisoning: move victim to fresh air. Breathing pure O₂ can give faster removal of CO

• Cyanide poisoning:
  • Cyanide inhibits the cytochrome oxidase enzyme of mitochondria
  • Two step treatment for cyanide poisoning:
    • 1) Give nitrites
      • Nitrites convert some hemoglobin to methemoglobin. Methemoglobin pulls cyanide away from mitochondria.
    • 2) Give thiosulfate.
      • Thiosulfate converts the cyanide to less poisonous thiocyanate.

Micturition (urination) is a process, by which the final urine is eliminated out of the body .
After being drained into the ureters, urine is stored in urinary bladder until being eliminated.

Bladder is a hollow muscular organ, which has three layers:

- epithelium : Composed of superficial layer of flat cells and deep layer of cuboidal cells.

- muscular layer : contain smooth muscle fibers, that are arranged in longitudinal, spiral and circular pattern . Detrusor  muscle is the main muscle of bladder. The thickening of detrusor muscle forms internal urinary sphinctor which is not an actual urinary sphincter. The actual one is the external urinary sphincter, which is composed of striated muscle and is a part of urogenital diaphragm.

- adventitia: composed of connective tissue fibers.

So: There are two phases of bladder function that depend on characterestics of its muscular wall and innervation :

1. Bladder filling : Urine is poured into bladder through the orifices of ureters. Bladder has five peristaltic contraction per minute . These contraction facilitate moving of urine from the ureter to the bladder as prevent reflux of urine into the ureter.. The capacity of bladder is about  400  ml. But when the bladder start filling its wall extends and thus the pressure is not increased with the increased urine volume.

2. Bladder emptying : When bladder is full stretch receptors in bladder wall are excited , and send signals via the sensory branches of pelvic nerves to the sacral plexus. The first urge to void is felt at a bladder volume of about 150 ml. In sacral portion of spinal cord the sensory signals are integrated and then a motor signal is sent to the urinarry blader muscles through the efferent branches of pelvic nerve itself.

In adult people the neurons in sacral portion could be influenced by nerve signals coming from brain ( Micturition center in pons ) that are also influenced by signals coming from cerebral cortex.

So: The sensory signals ,transmitted to the sacral region will also stimulate ascending pathway and the signals be also transmitted to the micturition center in the brain stem and then to the cerebrum to cause conscious desire for urination.

If micturition is not convenient the brain sends signals to inhibit the parasympathetic motor neuron to the bladder via the sacral neurons. 

It also send inhibitory signal via the somatomotor pudendal nerve to keep external urinary sphincter contracting.

When micturition is convenient a brain signal via the sacral neurons stimulate the parasympathetic pelvic nerve to cause contraction of detruser muscle via M-cholinergic receptors and causes relaxation of external urinary sphincter and the micturition occurs.

Sympathetic hypogastric nerve does not contribute that much to the micturition reflex. It plays role in prvrntion reflux of semen into urinary bladder during ejaculation by contracting bladder muscles.

Oxygen Transport in Blood: Hemoglobin

A.    Association & Dissociation of Oxygen + Hemoglobin

1.    oxyhemoglobin (HbO₂) - oxygen molecule bound
2.    deoxyhemoglobin (HHb) - oxygen unbound
    
H-Hb     +    O₂  <= === => HbO₂ + H+

3.    binding gets more efficient as each O₂ binds
4.    release gets easier as each O₂ is released

5.    Several factors regulate AFFINITY of O₂

a.    Partial Pressure of O₂
b.    temperature
c.    blood pH (acidity)
d.    concentration of “diphosphoglycerate” (DPG)

B.    Effects of Partial Pressure of O₂

1.  oxygen-hemoglobin dissociation curve

a.    104 mm (lungs) - 100% saturation (20 ml/100 ml)
b.    40 mm (tissues) - 75% saturation (15 ml/100 ml)
c.    right shift - Decreased Affinity, more O2 unloaded
d.     left shift- Increased Affinity, less O₂ unloaded

C.    Effects of Temperature
    
1.    HIGHER Temperature    --> Decreased Affinity (right)
2.    LOWER Temperature        --> Increased Affinity (left)

D.    Effects of pH (Acidity) 

1.    HIGHER pH    --> Increased Affinity (left)
2.    LOWER pH    --> Decreased Affinity (right) "Bohr Effect"
a.    more Carbon Dioxide, lower pH (more H+), more O2 release

E.    Effects of Diphosphoglycerate (DPG)

1.    DPG - produced by anaerobic processes in RBCs
2.    HIGHER DPG    > Decreased Affinity (right)
3.    thyroxine, testosterone, epinephrine, NE - increase RBC metabolism and DPG production, cause RIGHT shift

F.    Oxygen Transport Problems

1.    hypoxia - below normal delivery of Oxygen

a.    anemic hypoxia - low RBC or hemoglobin
b.    stagnant hypoxia - impaired/blocked blood flow
c.    hypoxemic hypoxia - poor lung gas exchange

2.    carbon monoxide poisoning - CO has greater Affinity than Oxygen or Carbon Dioxide 
 

Ingestion: Food taken in the mouth is

• ground into finer particles by the teeth,
• moistened and lubricated by saliva (secreted by three pairs of salivary glands)
• small amounts of starch are digested by the amylase present in saliva
• the resulting bolus of food is swallowed into the esophagus and
• carried by peristalsis to the stomach.

The Adrenal Glands

The adrenal glands are two small structures situated one at top each kidney. Both in anatomy and in function, they consist of two distinct regions:

• an outer layer, the adrenal cortex, which surrounds
• the adrenal medulla.

The Adrenal Cortex

cells of the adrenal cortex secrete a variety of steroid hormones.

• glucocorticoids (e.g., cortisol)
• mineralocorticoids (e.g., aldosterone)
• androgens (e.g., testosterone)

• Production of all three classes is triggered by the secretion of ACTH from the anterior lobe of the pituitary.

Glucocorticoids

They Effect by raising the level of blood sugar (glucose). One way they do this is by stimulating gluconeogenesis in the liver: the conversion of fat and protein into intermediate metabolites that are ultimately converted into glucose.

The most abundant glucocorticoid is cortisol (also called hydrocortisone).

Cortisol and the other glucocorticoids also have a potent anti-inflammatory effect on the body. They depress the immune response, especially cell-mediated immune responses. 

Mineralocorticoids

The most important of them is the steroid aldosterone. Aldosterone acts on the kidney promoting the reabsorption of sodium ions (Na⁺) into the blood. Water follows the salt and this helps maintain normal blood pressure.

Aldosterone also

• acts on sweat glands to reduce the loss of sodium in perspiration;
• acts on taste cells to increase the sensitivity of the taste buds to sources of sodium.

The secretion of aldosterone is stimulated by:

• a drop in the level of sodium ions in the blood;
• a rise in the level of potassium ions in the blood;
• angiotensin II
• ACTH (as is that of cortisol)

Androgens

The adrenal cortex secretes precursors to androgens such as testosterone.

Excessive production of adrenal androgens can cause premature puberty in young boys.

In females, the adrenal cortex is a major source of androgens. Their hypersecretion may produce a masculine pattern of body hair and cessation of menstruation.

Addison's Disease: Hyposecretion of the adrenal cortices

Addison's disease has many causes, such as

• destruction of the adrenal glands by infection;
• their destruction by an autoimmune attack;
• an inherited mutation in the ACTH receptor on adrenal cells.

Cushing's Syndrome: Excessive levels of glucocorticoids

In Cushing's syndrome, the level of adrenal hormones, especially of the glucocorticoids, is too high.It can be caused by:

• excessive production of ACTH by the anterior lobe of the pituitary;
• excessive production of adrenal hormones themselves (e.g., because of a tumor), or (quite commonly)
• as a result of glucocorticoid therapy for some other disorder such as
  • rheumatoid arthritis or
  • preventing the rejection of an organ transplant.

The Adrenal Medulla

The adrenal medulla consists of masses of neurons that are part of the sympathetic branch of the autonomic nervous system. Instead of releasing their neurotransmitters at a synapse, these neurons release them into the blood. Thus, although part of the nervous system, the adrenal medulla functions as an endocrine gland.The adrenal medulla releases:

• adrenaline (also called epinephrine) and
• noradrenaline (also called norepinephrine)

Both are derived from the amino acid tyrosine.

Release of adrenaline and noradrenaline is triggered by nervous stimulation in response to physical or mental stress. The hormones bind to adrenergic receptors  transmembrane proteins in the plasma membrane of many cell types.

Some of the effects are:

• increase in the rate and strength of the heartbeat resulting in increased blood pressure;
• blood shunted from the skin and viscera to the skeletal muscles, coronary arteries, liver, and brain;
• rise in blood sugar;
• increased metabolic rate;
• bronchi dilate;
• pupils dilate;
• hair stands on end (gooseflesh in humans);
• clotting time of the blood is reduced;
• increased ACTH secretion from the anterior lobe of the pituitary.

All of these effects prepare the body to take immediate and vigorous action.