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Physiology

The bulk of the pancreas is an exocrine gland secreting pancreatic fluid into the duodenum after a meal. However, scattered through the pancreas are several hundred thousand clusters of cells called islets of Langerhans. The islets are endocrine tissue containing four types of cells. In order of abundance, they are the:

  • beta cells, which secrete insulin and amylin;
  • alpha cells, which secrete glucagon;
  • delta cells, which secrete somatostatin, and
  • gamma cells, which secrete a polypeptide of unknown function.

Beta Cells

Beta cells secrete insulin in response to a rising level of blood sugar

Insulin affects many organs. It

  • stimulates skeletal muscle fibers to
    • take up glucose and convert it into glycogen;
    • take up amino acids from the blood and convert them into protein.
  • acts on liver cells
    • stimulating them to take up glucose from the blood and convert it into glycogen while
    • inhibiting production of the enzymes involved in breaking glycogen back down (glycogenolysis) and
    • inhibiting gluconeogenesis; that is, the conversion of fats and proteins into glucose.
  • acts on fat (adipose) cells to stimulate the uptake of glucose and the synthesis of fat.
  • acts on cells in the hypothalamus to reduce appetite.

Diabetes Mellitus

Diabetes mellitus is an endocrine disorder characterized by many signs and symptoms. Primary among these are:

  • a failure of the kidney to retain glucose .
  • a resulting increase in the volume of urine because of the osmotic effect of this glucose (it reduces the return of water to the blood).

There are three categories of diabetes mellitus:

  • Insulin-Dependent Diabetes Mellitus (IDDM) (Type 1) and
  • Non Insulin-Dependent Diabetes Mellitus (NIDDM)(Type 2)
  • Inherited Forms of Diabetes Mellitus

Insulin-Dependent Diabetes Mellitus (IDDM)

IDDM ( Type 1 diabetes)

  • is characterized by little or no circulating insulin;
  • most commonly appears in childhood.
  • It results from destruction of the beta cells of the islets.
  • The destruction results from a cell-mediated autoimmune attack against the beta cells.
  • What triggers this attack is still a mystery, although a prior viral infection may be the culprit.

Non Insulin-Dependent Diabetes Mellitus (NIDDM)

Many people develop diabetes mellitus without an accompanying drop in insulin levels In many cases, the problem appears to be a failure to express a sufficient number of glucose transporters in the plasma membrane (and T-system) of their skeletal muscles. Normally when insulin binds to its receptor on the cell surface, it initiates a chain of events that leads to the insertion in the plasma membrane of increased numbers of a transmembrane glucose transporter. This transporter forms a channel that permits the facilitated diffusion of glucose into the cell. Skeletal muscle is the major "sink" for removing excess glucose from the blood (and converting it into glycogen). In NIDDM, the patient's ability to remove glucose from the blood and convert it into glycogen is reduced. This is called insulin resistance. NIDDM (also called Type 2 diabetes mellitus) usually occurs in adults and, particularly often, in overweight people.

Alpha Cells

The alpha cells of the islets secrete glucagon, a polypeptide of 29 amino acids. Glucagon acts principally on the liver where it stimulates the conversion of glycogen into glucose (glycogenolysis) which is deposited in the blood.

Glucagon secretion is

  • stimulated by low levels of glucose in the blood;
  • inhibited by high levels, and
  • inhibited by amylin.

The physiological significance of this is that glucagon functions to maintain a steady level of blood sugar level between meals.

Delta Cells

The delta cells secrete somatostatin. Somatostatin has a variety of functions. Taken together, they work to reduce the rate at which food is absorbed from the contents of the intestine. Somatostatin is also secreted by the hypothalamus and by the intestine.

Gamma Cells

The gamma cells of the islets secrete pancreatic polypeptide. No function has yet been found for this peptide of 36 amino acids.

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

The Nervous System Has Peripheral and Central Units

  • The central nervous system (CNS) is the brain and spinal column
  • The peripheral nervous system (PNS) consists of nerves outside of the CNS
  • There are 31 pairs of spinal nerves (mixed motor & sensory)
  • There are 12 pairs of cranial nerves (some are pure sensory, but most are mixed)

The pattern of innervation plotted on the skin is called a dermatome

The Nervous System Has Peripheral and Central Units

  • The central nervous system (CNS) is the brain and spinal column
  • The peripheral nervous system (PNS) consists of nerves outside of the CNS
  • There are 31 pairs of spinal nerves (mixed motor & sensory)
  • There are 12 pairs of cranial nerves (some are pure sensory, but most are mixed)

The pattern of innervation plotted on the skin is called a dermatome

(RDS) Respiratory distress of Newborn
1.    hyaline membrane disease of the new born
2.    decrease in surfactant, Weak, Abnormal complience of chest wall
3.    Small alveoli, difficult to inflate, Alveoli tent to collapse, many of varied sizes
4.    decrease in O2 diffusion area, lung difficult to expand, in compliance

White Blood Cells (leukocytes)

White blood cells

  • are much less numerous than red (the ratio between the two is around 1:700),
  • have nuclei,
  • participate in protecting the body from infection,
  • consist of lymphocytes and monocytes with relatively clear cytoplasm, and three types of granulocytes, whose cytoplasm is filled with granules.

Lymphocytes: There are several kinds of lymphocytes, each with different functions to perform , 25% of wbc The most common types of lymphocytes are

  • B lymphocytes ("B cells"). These are responsible for making antibodies.
  • T lymphocytes ("T cells"). There are several subsets of these:
    • inflammatory T cells that recruit macrophages and neutrophils to the site of infection or other tissue damage
    • cytotoxic T lymphocytes (CTLs) that kill virus-infected and, perhaps, tumor cells
    • helper T cells that enhance the production of antibodies by B cells

Although bone marrow is the ultimate source of lymphocytes, the lymphocytes that will become T cells migrate from the bone marrow to the thymus where they mature. Both B cells and T cells also take up residence in lymph nodes, the spleen and other tissues where they

  • encounter antigens;
  • continue to divide by mitosis;
  • mature into fully functional cells.

Monocytes : also originate in marrow, spend up to 20 days in the circulation, then travel to the tissues where they become macrophages. Macrophages are the most important phagocyte outside the circulation. Monocytes are about 9% of normal wbc count

Macrophages are large, phagocytic cells that engulf

  • foreign material (antigens) that enter the body
  • dead and dying cells of the body.

Neutrophils

The most abundant of the WBCs. about 65% of normal white count  These cells spend 8 to 10 days in the circulation making their way to sites of infection etc  Neutrophils squeeze through the capillary walls and into infected tissue where they kill the invaders (e.g., bacteria) and then engulf the remnants by phagocytosis. They have two types of granules: the most numerous are specific granules which contain bactericidal agents such as lysozyme; the azurophilic granules are lysosomes containing peroxidase and other enzymes

Eosinophils : The number of eosinophils in the blood is normally quite low (0–450/µl). However, their numbers increase sharply in certain diseases, especially infections by parasitic worms. Eosinophils are cytotoxic, releasing the contents of their granules on the invader.

Basophils : rare except during infections where these cells mediate inflammation by secreting histamine and heparan sulfate (related to the anticoagulant heparin). Histamine makes blood vessels permeable and heparin inhibits blood clotting. Basophils are functionally related to mast cells.  . The mediators released by basophils also play an important part in some allergic responses such as hay fever and an anaphylactic response to insect stings.

Thrombocytes (platelets):

Thrombocytes are cellular derivatives from megakaryocytes which contain factors responsible for the intrinsic clotting mechanism. They represent fragmented cells  which contain residual organelles including rough endoplasmic reticulum and Golgi apparati. They are only 2-microns in diameter, are seen in peripheral blood either singly or, often, in clusters, and have a lifespan of 10 days.

Bleeding Disorders

A deficiency of a clotting factor can lead to uncontrolled bleeding.

The deficiency may arise because

  • not enough of the factor is produced or
  • a mutant version of the factor fails to perform properly.

Examples:

  • von Willebrand disease (the most common)
  • hemophilia A for factor 8 deficiency
  • hemophilia B for factor 9 deficiency.
  • hemophilia C for factor 11 deficiency

In some cases of von Willebrand disease, either a deficient level or a mutant version of the factor eliminates its protective effect on factor 8. The resulting low level of factor 8 mimics hemophilia A.

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) .
 

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