Physiology Test Cycle 1

General Physiology

Describe the types of tissue found in the human body

• Connective Tissue

  • Connect, anchor, and support structures of the body and perform additional functions

  • bone

  • adipose - stores fat

  • blood - suspends cells in a fluid matrix, carries everything

  • loose - most common, supports blood vessels

  • dense - like a ligament

  • cartilage -support

• Muscle Tissue

  • Skeletal: Voluntary, striated, long

  • Smooth: involuntary, short, spindle-shaped in the walls of organs

  • Cardiac: only in the heart, striated cells joined at intracellular junctions, involuntary

• Nervous Tissue

  • In the brain, spinal cord, and peripheral neurons

  • highly specialized and sensitive

  • initiate, integrate, and conduct electrical signals to other cells to regulate body functions

• Epithelial Tissue

  • Widespread through the body

  • specialized for secretion, absorption, excretion, and protection

  • Characterized by shape, arrangement and function

    • Cuboidal - cube shaped

    • Columnar - elongated

    • Squamous - flattened

    • Ciliated - hair-like protrusions

    • Simple - one layer

    • Striated - multiple layer

  • Attaches to other tissues at the basement membrane

  • Opposite sides of the tissue can preform different functions

  • Form tight junctions (close leakage)

  Discuss the major organ systems and their principal functions

• Circulatory - Transport of blood throughout the body

• Digestive - Digestion and absorption of nutrients and water, elimination of waste

• Endocrine - Regulation and coordination of many activities in the body, including growth, metabolism, reproduction, blood, pressure, water and electrolyte balance, and others

• Immune - Pathogen defense

• Integumentary - protection against the outside world (injury, pathogens, and dehydration) and temperature regulation

• Lymphatic - collect ECF and return it to circulation, immune defenses

• Musculoskeletal - support, protection, movement, blood cell production

• Nervous - regulation and coordination of many activities, detection and response to changes in environments, states of subconsciousness, learning, memory, emotion, etc

• Reproductive

  • Male - Production of sperm, transfer of sperm

  • Female - Production of eggs, provision of nutritive environment for the developing embryo and fetus, nutrition of the infant

• Respiratory - gas exchange, regulation of H+ concentration in body fluids

• Urinary - regulation of plasma through controlled excretion of salts, water, and organic wastes

  Define Homeostasis and describe how it is regulated

• Homeostasis is a dynamic process of give and take that maintains the processes of the body

• Homeostasis is regulated by:

  • Negative feedback system: countermeasure (works to oppose the stimulus)

    • Temperature control

    • Reflex action: rapid involuntary movement in response to a stimulus

      • touching a hot plate

        • muscles contract, glands release hormones

  • Positive feedback system: Let’s make it worse and see what happens (moves stimulus in the same direction

    • Uterine contractions in childbirth

  • Local Response: action takes place local to the stimulus (platelet coagulation on damaged blood vessels)

  • Chemical Messengers allow cells to communicate includes hormones, neurotransmitters, paracrine and autocrine substances

    • some potential inputs and outputs affect the “pool” of materials creating different states of total body balance

      • Net gain (positive balance)

      • Net loss (negative balance)

      • stable balance

  • Gap Junctions: sharing is caring, a physical channel between cells

  • Juxtacrine signaling: cell on cell action, a receptor on one cell connects to the signal molecule on another cell

  • Feedforward System: “Pavloving” our own self, works early to minimize the effect of a trigger

    • Circadian rhythms

  Describe the principle mechanisms used to regulate movement of biomolecules

• The cell membrane is picky (polar head with a non-polar tail) it really only likes small, non-polar, uncharged objects.

• Endocytosis: eat’em

  • fluid (pinocytosis)

  • eat (phagocytosis)

  • receptor-mediated

• Exocytosis: Yeet’em

  • movement out of the cell using vesicles

  • functions: replacement of cell membrane, addition of cell membrane, route of secretion

• Passive transport (no energy)

  • Diffusion - high concentration to low concentration

    • Things to remember - heat speeds things up, big things move slower, low density means faster diffusion, shorter distance or larger surface area means we’re quicker on the draw

    • Osmosis - diffusion of water

  • Diffusion through ion channels - selective and specific, determined by pore size, charge, and binding sites, can exist as open or closed gates

    • Ligand

    • Voltage - depend on membrane potential, molecules just slide on in, no need to bind

    • Mechanical

  • Facilitated diffusion - a carrier protein (GLUTS) that spands the membrane has a binding site for a particular molecule (Glucose) when glucose binds the carrier protein changes it shape and pushes the molecule to the other side of the membrane. The carrier protein then returns to it OG shape.

    • Depends on solute concentration, transport affinity, number of transports, speed of conformational change

• Active Transport - gotta have that ATP in some way, moves molecules against the gradient (low to high)

  • Primary - direct use of ATP

    • NA+/K+ATPase (main control of membrane potential)

  • Secondary - electrochemical gradient plus another molecule

    • transporters have 2 binding sites where one molecule kinda hitches a ride with the ion.

    • Cotransporters: same direction

    • Countertransporters: opposite direction

  Discuss the influence of osmolarity and tonicity on movement of water across membranes

• Important tip to remember is that water chases salt.

• Osmolarity - the total solute concentration of a solution

  • So lets say we have one mol of CaCl2 (3 solvents) in 0.5 L of solution. We would have 6 milliosmols in 1 liter.

    • its based on the number of solvents, so each element in a molecule counts as one

  • High osmolarity means low water content

• Hypertonic Solutions have a high salt content, water will rush out of the cell (chasing the salt) cell shrinks

• Isotonic solutions are pretty close to whats already in the body so the water just kinda chills. (0.9 NaCl)

• Hypotonic solutions have a low salt content so the water is going to rush inside of the cell to get to the more saltier area. Cell expands

Hematology

Describe the components of blood

• Blood is made up of formed elements (WBCs and RBCs) and Plasma which is just cell fragments (platelets)

• Hematocrit (Hct) is the percentage that formed elements make up in the blood

  • normal Hct is about 45%

  • Anemia Hct is about 30%

    • No enough RBCs

    • Anemic patients may dehydrate themselves so hematocrit rises, which will decrease symptoms

  • Polycythemia Hct is about 70%

    • Too many RBCs, blood is thicc and the heart has to work harder to move it

• If a patient is dehydrated the plasma (mostly water) is depleted this will increase the fraction of the formed elements aka raising the Hct.

  • 90% of blood is water, so less water means a high percentage of RBCs

• There are many organs that can affect the elements in the blood

  • The liver produces proteins that help maintain the osmotic pressure, these work to pull water back into the blood vessels (water chases salt)

Discuss the synthesis and functions of various blood cells

• Red Blood Cells - main function is gas exchange

  • Made in the red bone marrow

  • Live about 120 days

  • Recycled in liver and spleen

• Reticulocytes - Baby RBCs, still contain ribosomes

  • Anemic patients will have increase numbers of Reticulocytes as they are trying to make up the difference

• Platelets - come from megakaryocytes and clot the blood

• Blast cell Lines

  • Promyelocyte → Band → neutrophils

    • A left shift is an increase in bands and present in infection as the body is trying to fight it off an infection

  • Monocytes

    • Monocytes become macrophages in the tissue

• Eosinophils used to fight parasites and are a factor in immediate hypersensitivity reactions

• Basophils secrete histamine and heparin

• Bone Marrow Lymphocyte Line

  • B cells - immunoglobulins on surface

  • T cells -

Differentiate the major forms of anemia and know the causes

• On a CBC anemia will look like low HGB, low RBCs.

• Next we look at the MCV which is the mean cell volume

  • Microcytic anemia - low MCV

    • Iron Deficiency Anemia

  • Normocytic Anemia - MCV is in range

    • Anemia of Chronic disease (usually in CKD patients)

  • Macrocytic - High MCV

    • Folate or B12 deficiency Anemia

      • B12 is a vitamin that comes from eating animal products and assist in the uptake of folic acid.

        • Vegans have a low B12

      • Patients who have had a gastric bypass, are unable to absorb vitamins in their stomach, including B12

Discuss the key steps of hemostasis

1. A injury occurs in a vessel

2. Vascular spasm (aka vasoconstriction)

   • decrease the blood loss

   • hurt endothelial cells release endothelin which will activated smooth muscle contraction

   • Myogenic Mechanism

   • Nociorecptor activation

3. Platelet Plug Formation

   1. Injured endothelials secret vWF (von Wilderbraun’s factor) which can attach to the exposed collagen

   2. Platelets bind vWF and get activated.

   3. Platelets secrete ADP, Thromboxane A2, serotonin which activate more platelets (platelet aggregation)

      • Platelets are linked by fibrinogen.

      • Thromboxane A2 and serotonin bind to the smooth muscle and cause contraction, increasing the vascular spasm

4. coagulation

5. Clot retraction and repair

   1. platelet contraction

   2. secretion of platelet derived growth factor

   3. Secretion of vascular endothelial growth factor

6. Fibrinolysis (Clot busting)

   • Tissue plasminogen activator (tPA) on the cell membrane activates plasminogen (which is floating around) into Plasmin (aka PAC-Man)

   • Plasmin starts degrading fibrin mesh this will release D-dimer and Fibrinogen

     • D-dimer is an important marker for people with clots

Diagram the Blood Clotting Cascade

The liver is constantly creating clotting proteins that are floating around the bloodstream, but 9 times out of 10 they are usually inactivated

(Ca2+ is factor IV)

Intrinsic Pathway

More powerful

1. Factor XII floats on by our platelet plug, they interact. Factor XII is activated (XIIa).

2. Factor XI is activated by XIIa into XIa

3. Factor XIa activates IX into IXa

4. IXa activates VIII and they form a complex but they need the cofactor Ca+ and PF3 (platelet factor 3).

5. The Complex activates X to Xa. (common pathway starts here)

6. Xa reacts with V, PF3, and Ca2+ to form the prothrombin activator.

7. The Prothrombin activator which activates II (thrombin) into IIa

8. IIa reacts with fibrinogen (liquid-like) and links them together to form fibrin (jelly-like). IIa also activates XIII (using calcium) into XIIIa

9. XIIIa cross-links the fibrin strands to create a mesh to hold the platelet plug in place (no embolisms in this house)

10. The fibrin mesh is laid over the platelet plug so it cannot go anywhere

Extrinsic Pathway

Lightning Mcqueen (fast), weaker

1. When Tissues are injured they produce factor III which reacts with factor VII converting it to VIIa

2. VIIa can stimulate the activation of IX (intrinsic) or activate X (Common)

Define the natural anti-clotting system

• NO and PGI2 which is secreted by normal epthelial blood cells these molecules keep the platelet from activating

• Heparin-sulfate is bound to the plasma membrane and binds anti-thrombin III. The Activation of anti-thrombin 3 cleaves and inactivates, clotting factor II, IX, X.

• Thrombomodulin binds thrombin (factor II). This tag teams binds and activates protein C. This activation allows for protein C to degrade/inhibit factor V and VIII

• tPA on cell membranes will activate plasmin to break down the clot

Understand the mechanism of action of aspirin, heparin, warfarin, tPA, as well as overdose treatments

• tPA given in acute ischemic strokes to break up the clot.

  • Gotta have CT results showing ischemic and not hemorrhagic or you’ll kill’em

• Heparin keeps blood naturally thin by interfering with antithrombin III of endothelial cells

• Aspirin inhibits cyclooxygenase which decreases Thromboxane A2 and prostaglandin production

  • A low dose (84 mg) can be taken daily to lower the risk of stroke or heart attack because it “calms down” the clotting system

  • A high dose knocks out more of the clotting system

• Warfarin affects the the creation of clotting factors by blocking the integration of vitamin K

  • To combat an overdose of warfarin you would use a vitamin K

Immunology

Describe the cells and cytokines involved in immune response (CELL LINES (see hematology))

• Leukocytes (WBCs)

  • Neutrophils

    • made in the bone marrow

    • phagocytosis

    • release chemicals involved in inflammation leads to vasodilation and chemotaxis

  • Basophils

    • made in the bone marrow

    • similar to Mast cells (involved in allergies)

  • Eosinophils

    • made in bone marrow

    • parasite fighters

    • allergic reactions

  • Monocytes

    • Made in the bone marrow

    • enter into tissues and transform into macrophage

• Cytokines (messages from cells, dispatch team)

  • We got a ton of chemicals that work in tandem to activate the process of an immune response (immune and adaptive)

  • promoters and messengers

  • Redundancy and Cross talk

    • IL-1, TNF-alpha, IL-6

      • come from antigen presenting cells

      • target helper Ts and induce fever, stimulate systemic response

    • IL-2

      • come from most immune cells

      • target helper T

Discuss the role of lymphocytes in immune responses

• Lymphocytes are the B and T cells as well as the NK cells

  • B cells initiate antibody response

    • mature in the bone marrow

  • T cells have two types CD8+ (cytotoxic) and CD4+ (helper)

    • mature in the thymus

  • NK (natural killer cells)

Explain the innate and adaptive immune responses - whats the same what’s different

• Innate (maybe she’s born with it) gives us time to create an adaptive immunity, recruits immune cells to infection sites (the person calling 911)

• Defense at body surface

  • intact skin - barrier from infection

  • Hair in the nose

  • coughing, sneezing - expels potential infections

  • salivary glands

  • lacrimal glands

  • stomach acid - HCl acid, eats away the bad guys

  • mucus - makes it hard to move

  • ciliary action - captures the bad guy

• Inflammation

• Stages of inflammation

  1. Bacteria is introduced (Example: splinter in hand)

  2. Cytokines cause vasodilation and capillary permeability (makes it easy for help to get in)

     • Neutrophils (first responders) are recruited; margination

  3. Diapedesis results in neutrophils entering the affected tissue

  4. Bacteria is eaten by the neutrophils, capilliaries return to normal

• Chemotaxis

  • damaged tissue releases cytokines, margination (WBCs bind to capillary walls so they can get all up in the tissue), diapedesis (gettin all up in the tissue), chemokines

• Killing by phagocytes

  • Certain carbs or lipids = PAMPS

  • opsonin - seasoning for phagocytes (makes the antigen look tastier to the phagocytes)(antibody or innate substance)

    • important in tissue repair

  • Inside the macrophage

    • endocytosis forms a phagosome, these connect with lysosomes (phagolysosome) who’s chemicals breakdown the bacteria, dead bacteria, exocytosis of remnants

  • Phagocytes do other things (not just big back behavior)

    • release of cytokines to continue the immune response

    • Helps regulate the inflammatory process (inflammatory mediators)

    • Activation of clotting/anticlotting pathways

    • Hormonal regulation of systemic response

    • Doubles down - extracellular removal of microbes

• Complement Cascade

  • Bacteria (C3b) bind C3b receptors on phagocytes

    • locks it down (committed relationship), makes it efficient

  • Direct destruction via the MAC

  • Release of cytokines

• Interferons

  • A type of cytokine

    • two families (I and II)

  • Work as an autocrine, paracrine, and endocrine agent

  • inhibits viral replication inside the cell

    • Cancer cells can mess with this factor, makes the body think they’re normal cells

• Toll-like Receptors

  • Found on the surface of macrophages and dendritic cells

  • Release cytokines

    • IL-1, Il-2, Tumor necrosis factor

  • PAMPs (pathogen-associated molecular receptors)

    • pattern recognition of the bad guys and releases cytokines to begin the immune response

• Adaptive is specific

  • lymphocytes are specific to their antigen, they have got to recognize and then clonal expand.

  • Lymphocytes are created in the thymus (Ts) and bone marrow (Bs) which are primary lymphoid organs

    • secondary lymphoid organs are sites where there can be lots of antigens (mouth, spleen, lymph nodes, etc).

      • Lymphocytes will divide here

    • Humoral response (antibody mediated)

      • activated B cells (antibody-antigen action and the go ahead from CD4+ Ts)

      • hang out in lymphoid tissue

      • Antibodies

        • multiple classes (IgM, IgG, ETC.)

        • 2 heavy chains, 2 light chains

        • variable ends is where antigens bind

        • Constant ends are the same for most classes

        • IgM and IgG make up the bulk of specific immunity against bacteria and viruses in the ECF

        • IgE mediates immediate hypersensitivity and parasitic infections

        • IgA protects mucous membranes (think GI, respiratory, GU) and is secreted in breast milk (passive immunity)

        • IgD’s function is unclear

      • Bacteria gets in, antibody of B cell binds, B cell is activated by helper Ts (IL-2), clonal expansion into plasma (antibody making) and memory cells (so we’re quicker next time)

      • Antibodies only put a target on the back of a pathogen

        • enhance phagocytosis (opsonin)

        • active in complement system

        • Antibody Dependent Cytotoxity

          • Brings those NK cells into play

    • Cell Mediated Responses (T cell mediated)

      • Cytotoxic (CD8+)

        • attack cells - bind and secrete deadly chemicals (perforin)

        • Bind MHC I

        • Target infections inside the cell

      • Helper (CD4+)

        • absolutely necessary in activation of Bs, cytotoxic Ts, and macrophages, and NK

        • Keeps the body from attacking self

        • Bind MHC II

      • T Cell receptors - MHCs

        • MHCs have to bind to a presented complex where the cell breaks down the antigen and packages it up

        • 2 Classes

          • MHC I - found on every cell except RBCs

          • MHC II - only found on macrophages, dendritic cells, and B Cells

Describe the role of antigen presenting cells in promoting immune responses

• Gotta recognize we don’t want a reaction against self or non-dangerous things aka provides specificity

• Macrophages, dendritic cells, and B cells (CLASS II MHC) eat a antigen and present the epitopes on its MHC II. Presented to Helper Ts

  • To activate the Helper Ts we still need a costimulus (provable self protein) and IL-1 and TNF-alpha

• Any cell (basically) can act as a antigen presenting cell for cytotoxic Ts

  • Antigens can arise from inside the cell (the call is coming from inside the house)

    • cancer or virus

  • These are processed with MHC I and exocytosis and presented to the Cytotoxic Ts

• NK Cells are lymphocytes but not antigen specific, no b or t cell receptors, they are enhanced by helper Ts

  • when enhanced by T helper cells NKs can kill intracellular viruses and cancer cells

    • Since NKs can secrete IL-2 they can increase their own response

Discuss the immune-tolerance immunity and immune memory

• Immune Tolerance

  • Look at some point your body made antibodies and T cells against your own self

    • Clonal deletion - testing your T/B cells if they fail they die

    • Clonal inactivation - if your T/B cells start doing to much they get fired

    • The costimulus is only released if the antigen-presenting cells find something dangerous

• Immune Memory

  • As a part of clonal expansion, B cells will divide into memory B cells so we’re quicker next time

  • Active immunity - exposing the patient to the antigen

    • slow

    • vaccines

  • Passive immunity - direct transfer of antibodies

    • not long lived but fast

    • Antibodies from mom to baby

  • When treating Rabies you don’t have time to wait for the active immunity from the vaccine to kick in, so you also give them human rabies immunoglobulin (passive) to hold them over

Identify systemic manifestations or responses to infection

• A response of organs and tissues that are away from the site of infection/immune response

• AKA acute phase responses - no indicators of disease

• Usually triggered by cytokines released from macrophages

• Examples -

  • Fever (brain)

  • secretion of acute phase proteins by the liver

    • liver also retains zinc and iron which are necessary for bacterial replication

  • Increase of release of WBCs

  • lipolysis - increase in available energy

  • Cortisol is dumped

    • STEROIDS SUPPRESS THE IMMUNE SYSTEM (NEGATIVE FEEDBACK)

Explain the factors that might alter the resistance to infection

• Protein (malnutrition) - no amino acids for essential proteins

  • single greatest contributor to decreased resistance to disease

• pre-existing disease

  • like DM

  • AIDs (kills CD4+ cells)

    • Caused by HIV which is a rRNA virus so hella high viral replication

• Stress

  • low stress is good

  • high stress can make it worse

• Moderate exercise

• Genetic concerns

  • some people don’t make T/B cells (bubble boys)

• the amount of sleep

• Antibiotics

  • can disrupt bacterial cell-wall synthesis, protein synthesis, DNA replication

    • won’t affect the replication of human cells

  • BE CAREFUL

    • allergic reactions

    • some are toxics

    • bacteria can develop resistance

Summarize the common harmful or unwanted, human immune responses

• Graft rejection

  • transplanted organs get attacked by cytotoxic Ts

    • have to do with a difference of MHCs, cytotoxic Ts target the MHC class I proteins on the transplanted organ

  • Cyclosporine and steroids suppress rejection but you gotta take them FOREVER

    • non specific immuno-suppression so the entire immune system is messed with

• Transfusion rejection

  • Has to do with the antigens already found on our blood cells (A,B,O)

  • B cell response

    • A blood type people have antibodies against B

    • B blood type people have antibodies against A

    • AB blood type people have no antibodies against these antigens

    • O people have both antibodies (A and B)

  • recipients antibodies hemolyze the transfused cells

  • Gotta cross-match (unless its a code)

  • Rh negative vs. positive

    • Has to be exposed if they are Rh negative for there to be response.

    • If a mother is Rh- and in her first pregnancy is Rh+ baby is fine, mom gets exposed to the antigen

    • in future pregnancies the antibodies are already there so they can cross the placenta and mess with the baby leading to hemolytic disease of a newborn.

      • can prevent with passive immunity to mitigate the antibody response

• Hypersensitivity (allergies)

  • immune response causes the damage

  • 1st exposure causes sensitization, following immune exposures lead to the issues

  • Immediate (allergy)

    • most common and rapid onset, usually at the entry point of the allergen

    • antibody (IgE) mediated

    • IgE antibodies bind to Mast Cells (constant chain part) this is gonna trigger the release of histamines and other cytokines initiating a local inflammatory response

    • Anaphylaxis may result if a large amount of allergen is seen noted by vasodilation and bronchial constriction

    • Late-phase reaction - eosinophils secrete more inflammatory mediators and further sensitize the tissue so less allergen is needed

      • Eosinophils were originally important in killing parasites

  • Cytotoxic

    • Mediated by antibodies as in hemolytic disease of a newborn

  • Immune-complex

    • mediated by antigen-antibody complexes in their tissues, get trapped in capillary walls.

    • Immune complexes activate complement which can affect the tissue around the area

  • Delayed

    • TB Skin test

• Autoimmune Disease

  • due to attacking self (no clonal deletion or inactivation)

  • Examples: MS, Type I DM, RA

• Excessive inflammatory resposnses

  • Septic Shock

    • Secretion of nonspecific toxins, if there’s a lot of them you can kill the patient

      • the cytokines not the bacteria that causes septic shock

    • vasodilation (decreased bp)

    • high fevers

  • HIV can attack microglia cells which can cause “dementia”

Endocrinology

Describe and recognize the selected hormones’ synthesis, transport, metabolism, and excretion

• Amine Hormones (AKA the catecholamines, thyroid hormones, and dopamine)

  • Catecholamines are made in the adrenal medulla by chromaffin cells that synthesize and release Epi and NorEpi

  • Amines are transported unbound in blood and interact with receptors on cell surface

  • Amines have a short life span (minutes-hours) and are inactivated by enzymes in the blood

• Peptide hormones

  • Synthesized on ribosomes as pre-prohormones, cleaved by proteolytic enzymes in the rough ER into pro-hormones, packaged into vesicles by the golgi apparatus where the prohomone is cleaved into its active hormone and “left overs,” released via exocytosis

  • Transported unbound in blood and interact with receptors on cell surface

  • Short life span and are inactivated by enzymes in the blood

• Steroid hormones

  • In the mitochonidria, cholesterol is converted to pregnenolone using the cytochrome 450 pathway and dehydrogenases. Intermediates are shuttle between the smooth ER and the mitochondria, diffuse into the blood

  • Since steroid hormones are lipophilic they need a protein buddy to travel through the blood. They bind intracellular receptors

  • Resistant to enzyme degradation and have a long life span (hours to days)

• Thyroid Hormones (technically Amines but they’re getting their own sections)

  • Thyroid hormone is tightly regulated, when low levels are indicated the hypothalamus will release TRH which leads to the anterior pituitary releasing TSH which will increase protein synthesis in follicular epithelial cells of the thyroid. In the thyroid, Iodide is cotransported in with Na+, iodide will then diffuse across the follicle cell and into the lumen of the colloid, there it is oxidized and attached to a ring of tyrosine in thyroglobulin (TG), the iodinated rings of one MIT or DIT is added to a DIT at another spot (this determines T3 vs T4), endocytosis of thyroglobulin containing T3 and T4 molecules, Thyroglobulin is cleaved, at this point iodide can either be recycled or the hormones can be secreted

  • Thyroid hormones require a protein buddy in the blood and bind intracellular receptors

  • T4 is activated into T3 by metabolism (deiodinases)

Compare and Contrast the general characteristics of the presented hormones and hormone classes

• Peptides and catecholamines bind to receptors on the cell membrane and free float in the plasma

• Peptides and catecholamines are short-lived (minutes to hours) and quickly inactived by enzymes in the blood

• Protein-bound fractions of steroid hormones a resistant to enzymatic degradation and have a long lifespan (hours to days)

• Steroids and thyroid hormones need a protein buddy in the plasma and operate on intracellular receptors

• Testosterone (steroid androgen) and thyroxine (amine thyroid) have little metabolic activity until they are activated in the target tissue

Differentiate between individual mechanisms of action of the selected hormones on their target tissues

• Specific receptors on target cells respond to specific hormones

  • Up regulation increase hormone receptors to increase sensitivity

  • Down regulation decrease in the number of hormone receptors due to high hormone concentrations to decrease sensitivity

  • Permissive action (permissiveness) is where the presence of one hormone is required for full activity of a second hormone

    • One hormone acts to up or down regulate the number of receptors for a second hormone

    • Example Thyroid hormone and Epi

      • Neither thyroid hormones or Epinephrine can mobilize fatty acid from triglyceride stores in adipose. Thyroid hormones plus epi up-regulated epi receptors to allow for maximal effect

• Thyroid Hormones have major 3 functions: metabolic actions, permissive actions, growth and development

  • Metabolic action: maintains energy for sodium-potassium pump and represents a significant portion of a person’s total generated heat

    • works on the small intestine to metabolize carbs

    • Works on the adipocytes to metabolize lipids

  • Permissive action

    • Necessary for GH release

    • up-regulates Beta receptors in many tissues (permissive to epi)

  • Growth and development

    • Helps in the synthesis of axon terminals, synapses, dendrites, myelin sheaths

    • required in pregnancy for proper development

      • w/o it we get congenital hypothyroidism (cretinism)

    • Required in adults for nerve and muscle reflexes as well as normal cognition

• PTH works to maintain calcium balance

  • Bones: breakdown (osteoclasts)

  • Kidneys: increase calcium uptake and converts vitamin D to calcitrol

• Calcitrol also helps in calcium balance

  • works on intestine to increase calcium absorbtion

• Calcitonin the anti-flash to PTH

  • Bones: works to remodel bones (osteoblasts)

  • Kidneys: works to decrease calcium uptake

• Cortisol

  • Muscles: works to increase amino acids in the plasma and to release glucose from muscular glycogen

  • Liver: increase glucose through hepatic gluconeogenesis

  • Adipose: release glycerol and free fatty acids

  • Pancreas: decrease insulin, increase glucogon to increase gluconeogenesis and lipolysis

  • Permissive to glucagon and epi

• Epi and Norepi (Norepi only binds alpha-1, beta-1)

  • Alpha-1 receptors: increased intracellular calcium which leads to vasoconstriction leading to increase resistance which raises the MAP. Increased venous return. Pupil dilation. urine retention

  • Beta-1 receptors: Mostly in the heart, increased force and speed of contraction. No vessel influence. May influence renin to raise bp.

  • Beta-2 receptors: vasodilation, decreased systemic resistance and diastolic pressure. In the lungs it causes bronchodilation. In the liver, gluconeogenesis.

• Aldosterone works on the kidney to increase sodium and water retention

Recognize and differentiate between the various input that control hormone secretion

• Hypothalamus releases hyophysiotrophic hormones that act on the anterior pituitary gland

  • Corticotropin releasing hormone (CRH) → Stimulates secretion of ACTH

  • Thyrotropin releasing hormone (TRH) → stimulates secretion of TSH

  • Growth hormone releasing hormone (GHRH) → stimulates secretion of GH

  • Somatostatin (SS) → inhibits secretion of GH

  • Gonadotropin-releasing hormone (GnRH) → stimulates secretion of LH and FSH

  • Dopamine (DA) → inhibits prolactin

• Anterior pituitary hormones act on tissues

  • FSH and LH → act on the gonads to secrete hormones (estradiol/progesterone (female) and testosterone (men))

  • GH → stimulates the liver to secrete IGF-1 as well as other organs to synthesize proteins and metabolize lipids and carbohydrates

  • TSH → stimulates the thyroid to secrete T3 and T4

  • Prolactin → stimulates milk production

  • ACTH → stimulates the adrenal cortex to secrete cortisol

    • cytokines and vasopressin can also cortisol

• Hypothalamic-pituitary axis (HPA) describes the complex feedback loop

  • Short loop feedback: Negative feedback from the pituitary the the hypothalamus

    • GH inhibits GHRH release

  • Long loop feedback: Negative feedback from a pituitary target like the adrenal cortex

    • Cortisol inhibits CRH and ACTH release

• Lots of things can affect the rate of hormone secretions

  • Can be multiple, stimulatory, and/or inhibitory simultaneously

    • Ions or nutrients (no ingredients no cake)

    • Neurotransmitters

    • Other hormones

  • Secretion rate: balance of negative and positive inputs

• Example: Blood Sugar Control

  • Insulin is the only blood sugar lowering hormone in the body, its produced in the beta cells of the Islets of Langerhans

    • Promotes the storage of energy (glycogen, proteins, lipids)

    • suppresses the breakdown of nutrients

    • targets are the liver, muscles, and adipose tissue

      • these will pull glucose out of the ECF into the cell

    • release is controlled by blood glucose levels, glucagon, or indirectly by GH, glucocorticoids, and thyroid hormones

  • Glucagon is produced in the alpha cells of the Islets of Langerhans and work to increase blood glucose levels

    • increases blood glucose levels by stimulating insulin release