Physiology

Blood Pressure

Blood moves through the arteries, arterioles, and capillaries because of the force created by the contraction of the ventricles.

Blood pressure in the arteries.

The surge of blood that occurs at each contraction is transmitted through the elastic walls of the entire arterial system where it can be detected as the pulse. Even during the brief interval when the heart is relaxed — called diastole — there is still pressure in the arteries. When the heart contracts — called systole — the pressure increases.

Blood pressure is expressed as two numbers, e.g., 120/80.

Blood pressure in the capillaries

The pressure of arterial blood is largely dissipated when the blood enters the capillaries. Capillaries are tiny vessels with a diameter just about that of a red blood cell (7.5 µm). Although the diameter of a single capillary is quite small, the number of capillaries supplied by a single arteriole is so great that the total cross-sectional area available for the flow of blood is increased. Therefore, the pressure of the blood as it enters the capillaries decreases.

Blood pressure in the veins

When blood leaves the capillaries and enters the venules and veins, little pressure remains to force it along. Blood in the veins below the heart is helped back up to the heart by the muscle pump. This is simply the squeezing effect of contracting muscles on the veins running through them. One-way flow to the heart is achieved by valves within the veins

Exchanges Between Blood and Cells

With rare exceptions, our blood does not come into direct contact with the cells it nourishes. As blood enters the capillaries surrounding a tissue space, a large fraction of it is filtered into the tissue space. It is this interstitial or extracellular fluid (ECF) that brings to cells all of their requirements and takes away their products. The number and distribution of capillaries is such that probably no cell is ever farther away than 50 µm from a capillary.

When blood enters the arteriole end of a capillary, it is still under pressure produced by the contraction of the ventricle. As a result of this pressure, a substantial amount of water and some plasma proteins filter through the walls of the capillaries into the tissue space.

Thus fluid, called interstitial fluid, is simply blood plasma minus most of the proteins. (It has the same composition and is formed in the same way as the nephric filtrate in kidneys.)

Interstitial fluid bathes the cells in the tissue space and substances in it can enter the cells by diffusion or active transport. Substances, like carbon dioxide, can diffuse out of cells and into the interstitial fluid.

Near the venous end of a capillary, the blood pressure is greatly reduced .Here another force comes into play. Although the composition of interstitial fluid is similar to that of blood plasma, it contains a smaller concentration of proteins than plasma and thus a somewhat greater concentration of water. This difference sets up an osmotic pressure. Although the osmotic pressure is small, it is greater than the blood pressure at the venous end of the capillary. Consequently, the fluid reenters the capillary here.

Control of the Capillary Beds

An adult human has been estimated to have some 60,000 miles of capillaries with a total surface area of some 800–1000 m². The total volume of this system is roughly 5 liters, the same as the total volume of blood. However, if the heart and major vessels are to be kept filled, all the capillaries cannot be filled at once. So a continual redirection of blood from organ to organ takes place in response to the changing needs of the body. During vigorous exercise, for example, capillary beds in the skeletal muscles open at the expense of those in the viscera. The reverse occurs after a heavy meal.

The walls of arterioles are encased in smooth muscle. Constriction of arterioles decreases blood flow into the capillary beds they supply while dilation has the opposite effect. In time of danger or other stress, for example, the arterioles supplying the skeletal muscles will be dilated while the bore of those supplying the digestive organs will decrease. These actions are carried out by

the autonomic nervous system.
local controls in the capillary beds

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

Type of Hypoxia	O₂ Uptake in Lungs	Hemoglobin	Circulation	Tissue O₂Utilization
Hypoxic	Low	Normal	Normal	Normal
Anemic	Normal	Low	Normal	Normal
Ischemic	Normal	Normal	Low	Normal
Histotoxic	Normal	Normal	Normal	Low

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.

Oxygen Transport

In adult humans the hemoglobin (Hb) molecule

consists of four polypeptides:
- two alpha (α) chains of 141 amino acids and
- two beta (β) chains of 146 amino acids
Each of these is attached the prosthetic group heme.
There is one atom of iron at the center of each heme.
One molecule of oxygen can bind to each heme.

The reaction is reversible.

Under the conditions of lower temperature, higher pH, and increased oxygen pressure in the capillaries of the lungs, the reaction proceeds to the right. The purple-red deoxygenated hemoglobin of the venous blood becomes the bright-red oxyhemoglobin of the arterial blood.
Under the conditions of higher temperature, lower pH, and lower oxygen pressure in the tissues, the reverse reaction is promoted and oxyhemoglobin gives up its oxygen.

Contractility : Means ability of cardiac muscle to convert electrical energy of action potential into mechanical energy ( work).
The excitation- contraction coupling of cardiac muscle is similar to that of skeletal muscle , except the lack of motor nerve stimulation.

Cardiac muscle is a self-excited muscle , but the principles of contraction are the same . There are many rules that control the contractility of the cardiac muscles, which are:

1. All or none rule: due to the syncytial nature of the cardiac muscle.There are atrial syncytium and ventricular syncytium . This rule makes the heart an efficient pump.

2. Staircase phenomenon : means gradual increase in muscle contraction following rapidly repeated stimulation..

3. Starling`s law of the heart: The greater the initial length of cardiac muscle fiber , the greater the force of contraction. The initial length is determined by the degree of diastolic filling .The pericardium prevents overstretching of heart , and allows optimal increase in diastolic volume.

Thankful to this law , the heart is able to pump any amount of blood that it receives. But overstretching of cardiac muscle fibers may cause heart failure.

Factors affecting contractility ( inotropism)

I. Positive inotropic factors:

1. sympathetic stimulation: by increasing the permeability of sarcolemma to calcium.
2. moderate increase in temperature . This due to increase metabolism to increase ATP , decrease viscosity of myocardial structures, and increasing calcium influx.
3. Catecholamines , thyroid hormone, and glucagon hormones.
4. mild alkalosis
5. digitalis
6. Xanthines ( caffeine and theophylline )

II. Negative inotropic factors:

1. Parasympathetic stimulation : ( limited to atrial contraction)
2. Acidosis
3. Severe alkalosis
4. excessive warming and cooling .
5. Drugs ;like : Quinidine , Procainamide , and barbiturates .
6. Diphtheria and typhoid toxins.

Concentration versus diluting urine

Kidney is a major route for eliminating fluid from the body to accomplish water balance. Urine excretion is the last step in urine formation. Everyday both kidneys excrete about 1.5 liters of urine.
Depending on the hydrated status of the body, kidney either excretes concentrated urine ( if the plasma is hypertonic like in dehydrated status ) or diluted urine ( if the plasma is hypotonic) .
This occurs thankful to what is known as countercurrent multiplying system, which functions thankfully to establishing large vertical osmotic gradient .
To understand this system, lets review the following facts:
1. Descending limb of loop of Henle is avidly permeable to water.
2. Ascending limb of loop of Henly is permeable to electrolytes , but impermeable to water. So fluid will not folow electrolytes by osmosis.and thus Ascending limb creates hypertonic interstitium that will attract water from descending limb.
Pumping of electrolytes
3. So: There is a countercurrent flow produced by the close proximity of the two limbs.

Juxtamedullary nephrons have long loop of Henle that dips deep in the medulla , so the counter-current system is more obvious and the medullary interstitium is always hypertonic . In addition, peritubular capillaries in the medulla are straigh ( vasa recta) in which flow is rapid and rapidly reabsorb water maintaining hypertonic medullary interstitium.

In distal tubules water is diluted. If plasma is hypertonic, this will lead to release of ADH by hypothalamus, which will cause reabsorption of water in collecting tubules and thus excrete concentrated urine.

If plasma is hypotonic ADH will be inhibited and the diluted urine in distal tubules will be excreted as diluted urine.

Urea contributes to concentrating and diluting of urine as follows:

Urea is totally filtered and then 50% of filtrated urea will be reabsorbed to the interstitium, this will increase the osmolarity of medullary interstitium ( becomes hypertonic ). Those 50% will be secreted in ascending limb of loop of Henle back to tubular fluid to maintain osmolarity of tubular fluid. 55% of urea in distal nephron will be reabsorbed in collecting ducts back to the interstitium ( under the effect of ADH too) . This urea cycle additionally maintain hypertonic interstitium.

HEART DISORDERS

Pump failure => Alters pressure (flow) =>alters oxygen carrying capacity.
1. Renin release (Juxtaglomerular cells) Kidney
2. Converts Angiotensinogen => Angiotensin I
3. In lungs Angiotensin I Converted => Angiotensin II
4. Angiotensin II = powerful vasoconstrictor (raises pressure, increases afterload)
  1. stimulates thirst
  2. stimulates adrenal cortex to release Aldosterone
    (Sodium retention, potassium loss)
  3. stimulates kidney directly to reabsorb Sodium
  4. releases ADH from Posterior Pituitary
Myocardial Infarction
1. Myocardial Cells die from lack of Oxygen
2. Adjacent vessels (collateral) dilate to compensate
3. Intracellular Enzymes leak from dying cells (Necrosis)
  1. Creatine Kinase CK (Creatine Phosphokinase) 3 forms
    1. One isoenzyme = exclusively Heart (MB)
    2. CK-MB blood levels found 2-5 hrs, peak in 24 hrs
    3. Lactic Dehydrogenase found 6-10 hours after. points less clearly to infarction
  2. Serum glutamic oxaloacetic transaminase (SGOT)
    1. Found 6 hrs after infarction, peaks 24-48 hrs at 2 to 15 times normal,
    2. SGOT returns to normal after 3-4 days
4. Myocardium weakens = Decreased CO & SV (severe - death)
5. Infarct heal by fibrous repair
6. Hypertrophy of undamaged myocardial cells
  1. Increased contractility to restore normal CO
  2. Improved by exercise program
7. Prognosis
  1. 10% uncomplicated recovery
  2. 20% Suddenly fatal
  3. Rest MI not fatal immediately, 15% will die from related causes
Congenital heart disease (Affect oxygenation of blood)
1. Septal defects
2. Ductus arteriosus
3. Valvular heart disease
  1. Stenosis = cusps, fibrotic & thickened, Sometimes fused, can not open
  2. Regurgitation = cusps, retracted, Do not close, blood moves backwards

Structure of a nerve:

A peripheral nerve is arranged much like a muscle in terms of its connective tissue. It has an outer covering which forms a sheath around the nerve, called the epineurium. Often a nerve will run together with an artery and vein and their connective coverings will merge. Nerve fibers, which are axons, organize into bundles known as fascicles with each fascicle surrounded by the perineurium. Between individual nerve fibers is an inner layer of endoneurium.

The myelin sheath in peripheral nerves consists of Schwann cells wrapped in many layers around the axon fibers. Not all fibers in a nerve will be myelinated, but most of the voluntary fibers are. The Schwann cells are portrayed as arranged along the axon like sausages on a string. Gaps between the Schwann cells are called nodes of Ranvier. These nodes permit an impulse to travel faster because it doesn't need to depolarize each area of a membrane, just the nodes. This type of conduction is called saltatory conduction and means that impulses will travel faster in myelinated fibers than in unmyelinated ones.

The myelin sheath does several things:

1) It provides insulation to help prevent short circuiting between fibers.

2) The myelin sheath provides for faster conduction.

3) The myelin sheath provides for the possibility of repair of peripheral nerve fibers. Schwann cells help to maintain the micro-environments of the axons and their tunnel (the neurilemma tunnel) permits re-connection with an effector or receptor CNS fibers, not having the same type of myelination accumulate scar tissue after damage, which prevents regeneration.

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