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Physiology

The pancreas

The pancreas consists of clusters if endocrine cells (the islets of Langerhans) and exocrine cells whose secretions drain into the duodenum.

Pancreatic fluid contains:

  • sodium bicarbonate (NaHCO3). This neutralizes the acidity of the fluid arriving from the stomach raising its pH to about 8.
  • pancreatic amylase. This enzyme hydrolyzes starch into a mixture of maltose and glucose.
  • pancreatic lipase. The enzyme hydrolyzes ingested fats into a mixture of fatty acids and monoglycerides. Its action is enhanced by the detergent effect of bile.
  • 4 zymogens— proteins that are precursors to active proteases. These are immediately converted into the active proteolytic enzymes:
    • trypsin. Trypsin cleaves peptide bonds on the C-terminal side of arginines and lysines.
    • chymotrypsin. Chymotrypsin cuts on the C-terminal side of tyrosine, phenylalanine, and tryptophan residues (the same bonds as pepsin, whose action ceases when the NaHCO3 raises the pH of the intestinal contents).
    • elastase. Elastase cuts peptide bonds next to small, uncharged side chains such as those of alanine and serine.
    • carboxypeptidase. This enzyme removes, one by one, the amino acids at the C-terminal of peptides.
  • nucleases. These hydrolyze ingested nucleic acids (RNA and DNA) into their component nucleotides.

The secretion of pancreatic fluid is controlled by two hormones:

  • secretin, which mainly affects the release of sodium bicarbonate, and
  • cholecystokinin (CCK), which stimulates the release of the digestive enzymes.

Production of Hormones

The kidneys produce and interact with several hormones that are involved in the control of systems outside of the urinary system.

Calcitriol. Calcitriol is the active form of vitamin D in the human body. It is produced by the kidneys from precursor molecules produced by UV radiation striking the skin. Calcitriol works together with parathyroid hormone (PTH) to raise the level of calcium ions in the bloodstream. When the level of calcium ions in the blood drops below a threshold level, the parathyroid glands release PTH, which in turn stimulates the kidneys to release calcitriol. Calcitriol promotes the small intestine to absorb calcium from food and deposit it into the bloodstream. It also stimulates the osteoclasts of the skeletal system to break down bone matrix to release calcium ions into the blood.
 
Erythropoietin. Erythropoietin, also known as EPO, is a hormone that is produced by the kidneys to stimulate the production of red blood cells. The kidneys monitor the condition of the blood that passes through their capillaries, including the oxygen-carrying capacity of the blood. When the blood becomes hypoxic, meaning that it is carrying deficient levels of oxygen, cells lining the capillaries begin producing EPO and release it into the bloodstream. EPO travels through the blood to the red bone marrow, where it stimulates hematopoietic cells to increase their rate of red blood cell production. Red blood cells contain hemoglobin, which greatly increases the blood’s oxygen-carrying capacity and effectively ends the hypoxic conditions.
 
Renin. Renin is not a hormone itself, but an enzyme that the kidneys produce to start the renin-angiotensin system (RAS). The RAS increases blood volume and blood pressure in response to low blood pressure, blood loss, or dehydration. Renin is released into the blood where it catalyzes angiotensinogen from the liver into angiotensin I. Angiotensin I is further catalyzed by another enzyme into Angiotensin II.

Angiotensin II stimulates several processes, including stimulating the adrenal cortex to produce the hormone aldosterone. Aldosterone then changes the function of the kidneys to increase the reabsorption of water and sodium ions into the blood, increasing blood volume and raising blood pressure. Negative feedback from increased blood pressure finally turns off the RAS to maintain healthy blood pressure levels.

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 O2 Utilization

 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.

  • 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

Respiratory system plays important role in maintaining homeostasis . Other than its major function , which is supplying the cells with needed oxygen to produce energy and getting rid of carbon dioxide , it has other functions :

1 Vocalization , or sound production.
2 Participation in acid base balance .
3 Participation in fluid balance by insensible water elimination (vapors ).
4 Facilitating venous return .
5 Participation in blood pressure regulation : Lungs produce Angiotensin converting enzyme ( ACE ) .
6 Immune function : Lungs produce mucous that trap foreign particles , and have ciliae that move foreign particles away from the lung. They also produce alpha 1 antitrepsin that protect the lungs themselves from the effect of elastase and other proteolytic  enzymes

Blood Groups

Blood groups are created by molecules present on the surface of red blood cells (and often on other cells as well).

The ABO Blood Groups

The ABO blood groups are the most important in assuring safe blood transfusions.

Blood Group

Antigens on RBCs

Antibodies in Serum

Genotypes

A

A

Anti-B

AA or AO

B

B

Anti-A

BB or BO

AB

A and B

Neither

AB

O

Neither

Anti-A and anti-B

OO

When red blood cells carrying one or both antigens are exposed to the corresponding antibodies, they agglutinate; that is, clump together. People usually have antibodies against those red cell antigens that they lack.

The critical principle to be followed is that transfused blood must not contain red cells that the recipient's antibodies can clump. Although theoretically it is possible to transfuse group O blood into any recipient, the antibodies in the donated plasma can damage the recipient's red cells. Thus all transfusions should be done with exactly-matched blood.

The Rh System

Rh antigens are transmembrane proteins with loops exposed at the surface of red blood cells. They appear to be used for the transport of carbon dioxide and/or ammonia across the plasma membrane. They are named for the rhesus monkey in which they were first discovered.

There are a number of Rh antigens. Red cells that are "Rh positive" express the one designated D. About 15% of the population have no RhD antigens and thus are "Rh negative".

The major importance of the Rh system for human health is to avoid the danger of RhD incompatibility between mother and fetus.

During birth, there is often a leakage of the baby's red blood cells into the mother's circulation. If the baby is Rh positive (having inherited the trait from its father) and the mother Rh-negative, these red cells will cause her to develop antibodies against the RhD antigen. The antibodies, usually of the IgG class, do not cause any problems for that child, but can cross the placenta and attack the red cells of a subsequent Rh+ fetus. This destroys the red cells producing anemia and jaundice. The disease, called erythroblastosis fetalis or hemolytic disease of the newborn, may be so severe as to kill the fetus or even the newborn infant. It is an example of an antibody-mediated cytotoxicity disorder.

Although certain other red cell antigens (in addition to Rh) sometimes cause problems for a fetus, an ABO incompatibility does not. Rh incompatibility so dangerous when ABO incompatibility is not

It turns out that most anti-A or anti-B antibodies are of the IgM class and these do not cross the placenta. In fact, an Rh/type O mother carrying an Rh+/type A, B, or AB fetus is resistant to sensitization to the Rh antigen. Presumably her anti-A and anti-B antibodies destroy any fetal cells that enter her blood before they can elicit anti-Rh antibodies in her.

This phenomenon has led to an extremely effective preventive measure to avoid Rh sensitization. Shortly after each birth of an Rh+ baby, the mother is given an injection of anti-Rh antibodies. The preparation is called Rh immune globulin (RhIG) or Rhogam. These passively acquired antibodies destroy any fetal cells that got into her circulation before they can elicit an active immune response in her.

Rh immune globulin came into common use in the United States in 1968, and within a decade the incidence of Rh hemolytic disease became very low.

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

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