Red blood cell cycle:

RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. RBCs require Vitamin B12, folic acid, and iron. The lifespan of RBC averages 120 days. Aged and damaged red cells are disposed of in the spleen and liver by macrophages. The globin is digested and the amino acids released into the blood for protein manufacture; the heme is toxic and cannot be reused, so it is made into bilirubin and removed from the blood by the liver to be excreted in the bile. The red bile pigment bilirubin oxidizes into the green pigment biliverdin and together they give bile and feces their characteristic color. Iron is picked up by a globulin protein (apotransferrin) to be transported as transferrin and then stored, mostly in the liver, as hemosiderin or ferritin. Ferritin is short term iron storage in constant equilibrium with plasma iron carried by transferrin. Hemosiderin is long term iron storage, forming dense granules visible in liver and other cells which are difficult for the body to mobilize.

Some iron is lost from the blood due to hemorrhage, menstruation, etc. and must be replaced from the diet. On average men need to replace about 1 mg of iron per day, women need 2 mg. Apotransferrin (transferrin without the iron) is present in GI lining cells and is also released in the bile. It picks up iron from the GI tract and stimulates receptors on the lining cells which absorb it by pinocytosis. Once through the mucosal cell iron is carried in blood as transferrin to the liver and marrow. Iron leaves the transferrin molecule to bind to ferritin in these tissues. Most excess iron will not be absorbed due to saturation of ferritin, reduction of apotransferrin, and an inhibitory process in the lining tissue.

Erythropoietin Mechanism:

Myeloid (blood producing) tissue is found in the red bone marrow located in the spongy bone. As a person ages much of this marrow becomes fatty and ceases production. But it retains stem cells and can be called on to regenerate and produce blood cells later in an emergency. RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. This hormone triggers more of the pleuripotential stem cells (hemocytoblasts) to follow the pathway to red blood cells and to divide more rapidly.

It takes from 3 to 5 days for development of a reticulocyte from a hemocytoblast. Reticulocytes, immature rbc, move into the circulation and develop over a 1 to 2 day period into mature erythrocytes. About 1 to 2 % of rbc in the circulation are reticulocytes, and the exact percentage is a measure of the rate of erythropoiesis.

Cardiac Output:

Minute Volume = Heart Rate X Stroke Volume

Heart rate, HR at rest = 65 to 85 bpm  

Each heartbeat at rest takes about .8 sec. of which .4 sec. is quiescent period.

Stroke volume, SV at rest = 60 to 70 ml.

Heart can increase both rate and volume with exercise. Rate increase is limited due to necessity of minimum ventricular diastolic period for filling. Upper limit is usually put at about 220 bpm. Maximum heart rate calculations are usually below 200. Target heart rates for anaerobic threshold are about 85 to 95% of maximum.

Terms:

End Diastolic Volume, EDV - the maximum volume of the ventricles achieved at the end of ventricular diastole. This is the amount of blood the heart has available to pump. If this volume increases the cardiac output increases in a healthy heart.

End Systolic Volume, ESV - the minimum volume remaining in the ventricle after its systole. If this volume increases it means less blood has been pumped and the cardiac output is less.

EDV - ESV = SV

SV / EDV = Ejection Fraction The ejection fraction is normally around 50% at rest and will increase during strenuous exercise in a healthy heart. Well trained athletes may have ejection fractions approaching 70% in the most strenuous exercise.

Isovolumetric Contraction Phase - a brief period at the beginning of ventricular systole when all valves are closed and ventricular volume remains constant. Pressure has risen enough in the ventricle to close the AV valves but not enough to open the semilunar valves and cause ejection of blood. 

Isovolumetric Relaxation Phase - a brief period at the beginning of ventricular diastole when all valves are closed and ventricular volume is constant. Pressure in the ventricle has lowered producing closure of the semilunar valves but not opening the AV valves to begin pulling blood into the ventricle.

Dicrotic Notch - the small increase in pressure of the aorta or other artery seen when recording a pulse wave. This occurs as blood is briefly pulled back toward the ventricle at the beginning of diastole thus closing the semilunar valves.

Preload - This is the pressure at the end of ventricular diastole, at the beginning of ventricular systole. It is proportional to the End Diastolic Volume (EDV), i.e. as the EDV increases so does the preload of the heart. Factors which increase the preload are: increased total blood volume, increased venous tone and venous return, increased atrial contraction, and the skeletal muscular pump.

Afterload - This is the impedence against which the left ventricle must eject blood, and it is roughly proportional to the End Systolic Volume (ESV). When the peripheral resistance increases so does the ESV and the afterload of the heart. 

The importance of these parameters are as a measure of efficiency of the heart, which increases as the difference between preload and afterload increases

Gonadotropin-releasing hormone (GnRH)

GnRH is a peptide of 10 amino acids. Its secretion at the onset of puberty triggers sexual development.

Primary Effects

FSH and LH Relaese

Secondary Effects

Increases estrogen and progesterone (in females)

testosterone Relaese (in males)

Growth hormone-releasing hormone (GHRH)

GHRH is a mixture of two peptides, one containing 40 amino acids, the other 44.  GHRH stimulates cells in the anterior lobe of the pituitary to secrete growth hormone (GH).

Corticotropin-releasing hormone (CRH)

CRH is a peptide of 41 amino acids. Its acts on cells in the anterior lobe of the pituitary to release adrenocorticotropic hormone (ACTH) CRH is also synthesized by the placenta and seems to determine the duration of pregnancy.  It may also play a role in keeping the T cells of the mother from mounting an immune attack against the fetus

Somatostatin

Somatostatin is a mixture of two peptides, one of 14 amino acids, the other of 28. Somatostatin acts on the anterior lobe of the pituitary to

• inhibit the release of growth hormone (GH)
• inhibit the release of thyroid-stimulating hormone (TSH)

Somatostatin is also secreted by cells in the pancreas and in the intestine where it inhibits the secretion of a variety of other hormones.

Antidiuretic hormone (ADH) and Oxytocin

These peptides are released from the posterior lobe of the pituitary

CNS PROTECTION

- Bones of the Skull       Frontal, Temporal, Parietal, Sphenoid, Occipital

- Cranial Meninges         Dura mater, Arachnoid Space, Pia mater

- Cerebrospinal Fluid

Secreted by Chroid Plexi in Ventricles

Circulation through ventricles and central canal

Lateral and Median apertures from the 4th ventricle into the subarachnoid space

Arachnoid villi of the superior sagittal sinus return CSF to the venous circulation

Hydrocephalic Condition, blockage of the mesencephalic aqueduct, backup of CSF, Insertion of a shunt to drain the excess CSF

Neural Substrates of Breathing

A.    Medulla Respiratory Centers

Inspiratory Center (Dorsal Resp Group - rhythmic breathing) → phrenic nerve→ intercostal nerves→ diaphragm + external intercostals

Expiratory Center (Ventral Resp Group - forced expiration) → phrenic nerve → intercostal nerves → internal intercostals + abdominals (expiration)

1.    eupnea - normal resting breath rate (12/minute)
2.    drug overdose - causes suppression of Inspiratory Center

B.    Pons Respiratory Centers

1.    pneumotaxic center - slightly inhibits medulla, causes shorter, shallower, quicker breaths
2.    apneustic center - stimulates the medulla, causes longer, deeper, slower breaths

C.    Control of Breathing Rate & Depth

1.    breathing rate - stimulation/inhibition of medulla
2.    breathing depth - activation of inspiration muscles
3.    Hering-Breuer Reflex - stretch of visceral pleura that lungs have expanded (vagal nerve)

D.    Hypothalamic Control - emotion + pain to the medulla

E.    Cortex Controls (Voluntary Breathing) - can override medulla as during singing and talking

Water: comprises 60 - 90% of most living organisms (and cells) important because it serves as an excellent solvent & enters into many metabolic reactions

• Intracellular (inside cells) = ~ 34 liters
• Interstitial (outside cells) = ~ 13 liters
• Blood plasma = ~3 liters

40% of blood is red blood cells (RBCs)

plasma is similar to interstitial fluid, but contains plasma proteins

serum = plasma with clotting proteins removed

intracellular fluid is very different from interstitial fluid (high K concentration instead of high Na concentration, for example)

• Capillary walls (1 cell thick) separate blood from interstitial fluid
• Cell membranes separate intracellular and interstitial fluids

• Loss of about 30% of body water is fatal

Ions = atoms or molecules with unequal numbers of electrons and protons:

• found in both intra- & extracellular fluid
• examples of important ions include sodium, potassium, calcium, and chloride

Ions (Charged Atoms or Molecules) Can Conduct Electricity

• Giving up electron leaves a + charge (cation)
• Taking on electron produces a - charge (anion)
• Ions conduct electricity
• Without ions there can be no nerves or excitability
  • Na⁺ and K⁺ cations  
  • Ca²⁺ and Mg²⁺ cations  control metabolism and trigger muscle contraction and secretion of hormones and transmitters

Na+ & K+ are the Major Cations in Biological Fluids

• High K+ in cells, high Na+ outside
• Ion gradients maintained by Na pump (1/3 of basal metabolism)
• Think of Na+ gradient as a Na+ battery- stored electrical energy
• K+ gradient forms a K+ battery
• Energy stored in Na+ and K+ batteries can be tapped when ions flow

• Na+ and K+ produce action potential of excitable cells