Clinical Physiology 

Heart Failure : Heart failure is inability of the heart to pump the enough amount of blood needed to sustain the needs of organism .
It is usually called congestive heart failure ( CHF) .

To understand the pathophysiology  of the heart failure ,  lets compare it with the physiology of the cardiac output :
Cardiac output =Heart rate X stroke volume

Stroke volume is determined by three determinants : Preload ( venous return ) , contractility , and afterload    (peripheral resistance ) . Any disorder of these factors will reduce the ability of the heart to pump blood .

Preload : Any factor that decrease the venous return , either by decreasing the intravenous pressure or increasing the intraatrial pressure will lead to heart failure .

Contractility : Reducing the power of contraction such as in  myocarditis , cardiomyopathy , preicardial tamponade ..etc , will lead to heart failure .

Afterload : Any factor that may increase the peripheral resistance such as hypertension , valvular diseases of the heart may cause heart failure.

Pathophysiology : When the heart needs to contract more to meet the increased demand , compensatory mechanisms start to develope to enhance the power of contractility  . One of these mechanism is increasing heart rate , which will worsen the situation because this will increase the demands of the myocardial cells themselves . The other one is hypertrophy of the cardiac muscle which may compensate the failure temporarily but then the hypertrophy will be an additional load as the fibers became stiff  .

The stroke volume will be reduced , the intraventricular pressure will increase and consequently the intraatrial pressure and then the venous pressure . This will lead to decrease reabsorption of water from the interstitium ( see microcirculation) and then leads to developing of edema ( Pulmonary edema if the failure is left , and systemic edema if the failure is right) .

Reflexes

A reflex is a direct connection between stimulus and response, which does not require conscious thought. There are voluntary and involuntary reflexes.

The Stretch Reflex:

The stretch reflex in its simplest form involves only 2 neurons, and is therefore sometimes called a 2-neuron reflex. The two neurons are a sensory and a motor neuron. The sensory neuron is stimulated by stretch (extension) of a muscle. Stretch of a muscle normally happens when its antagonist contracts, or artificially when its tendon is stretched, as in the knee jerk reflex. Muscles contain receptors called muscle spindles. These receptors respond to the muscles's stretch. They send stimuli back to the spinal cord through a sensory neuron which connects directly to a motor neuron serving the same muscle. This causes the muscle to contract, reversing the stretch. The stretch reflex is important in helping to coordinate normal movements in which antagonistic muscles are contracted and relaxed in sequence, and in keeping the muscle from overstretching.

Since at the time of the muscle stretch its antagonist was contracting, in order to avoid damage it must be inhibited or tuned off in the reflex. So an additional connection through an interneuron sends an inhibitory pathway to the antagonist of the stretched muscle - this is called reciprocal inhibition.

The Deep Tendon Reflex:

Tendon receptors respond to the contraction of a muscle. Their function, like that of stretch reflexes, is the coordination of muscles and body movements. The deep tendon reflex involves sensory neurons, interneurons, and motor neurons. The response reverses the original stimulus therefore causing relaxation of the muscle stimulated. In order to facilitate that the reflex sends excitatory stimuli to the antagonists causing them to contract - reciprocal activation.

The stretch and tendon reflexes complement one another. When one muscle is stretching and stimulating the stretch reflex, its antagonist is contracting and stimulating the tendon reflex. The two reflexes cause the same responses thus enhancing one another.

The Crossed Extensor Reflex -

The crossed extensor reflex is just a withdrawal reflex on one side with the addition of inhibitory pathways needed to maintain balance and coordination. For example, you step on a nail with your right foot as you are walking along. This will initiate a withdrawal of your right leg. Since your quadriceps muscles, the extensors, were contracting to place your foot forward, they will now be inhibited and the flexors, the hamstrings will now be excited on your right leg. But in order to maintain your balance and not fall down your left leg, which was flexing, will now be extended to plant your left foot (e.g. crossed extensor). So on the left leg the flexor muscles which were contracting will be inhibited, and the extensor muscles will be excited

Red Blood Cells (erythrocytes)

• Women average about 4.8 million of these cells per cubic millimeter (mm³; which is the same as a microliter [µl]) of blood.
• Men average about 5.4 x 10⁶ per µl.
• These values can vary over quite a range depending on such factors as health and altitude.
• RBC precursors mature in the bone marrow closely attached to a macrophage.
• They manufacture hemoglobin until it accounts for some 90% of the dry weight of the cell.

• The nucleus is squeezed out of the cell and is ingested by the macrophage.

RBC have characteristic biconcave shape

Thus RBCs are terminally differentiated; that is, they can never divide. They live about 120 days and then are ingested by phagocytic cells in the liver and spleen. Most of the iron in their hemoglobin is reclaimed for reuse. The remainder of the heme portion of the molecule is degraded into bile pigments and excreted by the liver. Some 3 million RBCs die and are scavenged by the liver each second.

Red blood cells are responsible for the transport of oxygen and carbon dioxide.

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.

• Sensory:
  • Somatic (skin & muscle) Senses:
    Postcentral gyrus (parietal lobe). This area senses touch, pressure, pain, hot, cold, & muscle position. The arrangement is upside-down (head below, feet above) and is switched from left to right (sensations from the right side of the body are received on the left side of the cortex). Some areas (face, hands) have many more sensory and motor nerves than others. A drawing of the body parts represented in the postcentral gyrus, scaled to show area, is called a homunculus .
  • Vision:
    Occipital lobe, mostly medial, in calcarine sulcus. Sensations from the left visual field go to the right cortex and vice versa. Like other sensations they are upside down. The visual cortex is very complicated because the eye must take into account shape, color and intensity.
  • Taste:
    Postcentral gyrus, close to lateral sulcus. The taste area is near the area for tongue somatic senses.
  • Smell:
     The olfactory cortex is not as well known as some of the other areas. Nerves for smell go to the olfactory bulb of the frontal cortex, then to other frontal cortex centers- some nerve fibers go directly to these centers, but others come from the thalamus like most other sensory nerves
  • Hearing:
    Temporal lobe, near junction of the central and lateral sulci. Mostly within the lateral sulcus. There is the usual crossover and different tones go to different parts of the cortex. For complex patterns of sounds like speech and music other areas of the cortex become involved.
• Motor:
  • Primary Motor ( Muscle Control):
    Precentral gyrus (frontal lobe). Arranged like a piano keyboard: stimulation in this area will cause individual muscles to contract. Like the sensory cortex, the arrangement is in the form of an upside-down homunculus. The fibers are crossed- stimulation of the right cortex will cause contraction of a muscle on the left side of the body.
  • Premotor (Patterns of Muscle Contraction):
    Frontal lobe in front of precentral gyrus. This area helps set up learned patterns of muscle contraction (think of walking or running which involve many muscles contracting in just the right order).
  • Speech-Muscle Control:
    Broca's area, frontal lobe, usually in left hemisphere only. This area helps control the patterns of muscle contraction necessary for speech. Disorders in speaking are called aphasias.
• Perception:
  • Speech- Comprehension:
    Wernicke's area, posterior end of temporal lobe, usually left hemisphere only. Thinking about words also involves areas in the frontal lobe.
  • Speech- Sound/Vision Association:
    Angular gyrus, , makes connections between sounds and shapes of words

PHYSIOLOGY OF THE BRAIN

• The Cerebrum (Telencephalon) Lobes of the cerebral cortex

   

  1. Frontal Lobe
     1. Precentral gyrus, Primary Motor Cortex, point to point motor neurons, pyramidal cells: control motor neurons of the brain and spinal cord. See Motor homunculus
     2. Secondary Motor Cortex repetitive patterns
     3. Broca's Motor Speech area
     4. Anterior - abstract thought, planning, decision making, Personality
  2. Parietal Lobe
     1. Post central gyrus, Sensory cortex, See Sensory homunculus, size proportional to sensory receptor density.
     2. Sensory Association area, memory of sensations
  3. Occipital Lobe
     1. Visual cortex, sight (conscious perception of vision)
     2. Visual Association area, correlates visual images with previous images, (memory of vision, )
  4. Temporal Lobe
     1. Auditory Cortex, sound
     2. Auditory Association area, memory of sounds
  5. Common Integratory Center - angular gyrus, Parietal, Temporal & Occipital lobes
     1. One side becomes dominent, integrats sensory (somesthetic, auditory, visual) information
  6. The Basal nuclei (ganglia)
     1. Grey matter (cell bodies) within the White matter of cerebrum, control voluntary movements
  7. Cauadate nucles - chorea (rapi, uncontrolled movements), Parkinsons: (dopamine neurons of substantia nigra to caudate nucles) jerky movements, spasticity, tremor, blank facial expression
  8. The limbic system - ring around the brain stem, emotions(w/hypothalamus), processing of olfactory information

• The Diencephalon

   

  1. The Thalamus - Sensory relay center to cortex (primitive brain!)
  2. The Hypothalamus
     1. core temperature control"thermostat", shivering and nonshivering thermogenesis
     2. hunger & satiety centers, wakefulness, sleep, sexual arousal,
     3. emotions (w/limbic-anger, fear, pain, pleasure), osmoregulation, (ADH secretion),
     4. Secretion of ADH, Oxytocin, Releasing Hormones for Anterior pitutary
     5. Linkage of nervous and endocrine systems

• The Mesencephalon or Midbrain -

   

  1. red nucleus, motor coordination (cerebellum/Motor cortex),
  2. substantia nigra
• The Metencephalon
  1. The Cerebellum -
     1. Performs automatic adjustments in complex motor activities
     2. Input from Proprioceptors (joint, tendon, muscles), position of body in Space
        1. Motor cortex, intended movements (changes in position of body in Space)
     3. Damping (breaking motor function), Balance, predicting, inhibitory function of Purkinji cells (GABA), speed, force, direction of movement
  2. The Pons - Respiratory control centers (apneustic, pneumotaxic)
     1. Nuclei of cranial nerves V, VI, VII, VIII

• Myelencephalon

   

  1. The Medulla
     1. Visceral motor centers (vasomotor, cardioinhibtory, respiratory)
     2. Reticular Formation RAS system, alert cortex to incoming signals, maintenance of consciousness, arousal from sleep
     3. All Afferent & Efferent fibers pass through, crossing over of motor tracts
  2. Corpus Callosum: Permits communication between cerebralhemispheres
• Generalized Brain Avtivity
  1. Brain Activity and the Electroencephalogram(EEG)
     1. alpha waves: resting adults whose eyes are closed
     2. beta waves: adults concentrating on a specific task;
     3. theta waves: adults under stress;
     4. delta waves: during deep sleep and in clinical disorders
  2. Brain Seizures
     1. Grand Mal: generalized seizures, involvs gross motor activity, affects the individual for a matter or hours
     2. Petit mal: brief incidents, affect consciousness but may have no obvious motor abnormalities
  3. Chemical Effects on the Brain
     1. Sedatives: reduce CNS activity
     2. Analgesics: relieve pain by affecting pain pathways or peripheral sensations
     3. Psychotropics: alter mood and emotional states
     4. Anticonvulsants: control seizures
     5. Stimulants: facilitate CNS activity
  4. Memory and learning
     1. Short-term, or primary, memories last a short time, immediately accessible (phone number)
     2. Secondary memories fade with time (your address at age 5)
     3. Tertiary memories last a lifetime (your name)
     4. Memories are stored within specific regions of the cerebral cortex.
     5. Learning, a more complex process involving the integration of memories and their use to direct or modify behaviors
     6. Neural basis for memory and learning has yet to be determined.
• Fibers in CNS
  1. Association fibers: link portions of the cerebrum;
  2. Commissural fibers: link the two hemispheres;
  3. Projection fibers: link the cerebrum to the brain stem