Physiology Lecture Exam 1

G6PD/ Methemoglobin/ Anemia

-Glucose 6 phosphate dehydrogenase -most common inherited enzyme defect -X linked, mostly affects males -RBCs constantly exposed to high levels of free radicals (reactive oxygen species) -G6PD helps produce NADH which maintains levels of glutathione high in blood -RBCs are more vulnerable to oxidants, methemoglobin and denaturation of Hb results -Heinz bodies common -fava beans (favism), mediterranean descent -methemoglobin is formed when Hb binds to iron in ferric 3+ state, which cannot bind oxygen and forms methemoglobin -methemoglobin does not bind oxygen and cannot deliver oxygen to the tissues, which results in anemia: low oxygen carrying capacity

22.Describe the handling of iron by the body for delivery and removal of iron. Know the functions of transferrin, ferritin.

1. Free iron in intestines immediately combines with Protein Apotransferrin to form Transferrin 2. Transferrin is released into the blood to form Plasma Transferrin 3. Plasma Transferrrin delivers Iron to iron-deficient cells 4. In the cytoplasm, Iron combines with Apoferritin to form Ferittin 5. If Apoferrritin cannot combine with all iron available, Iron will be stored as the insoluble toxic form Hemosiderrin Ferittin: Storage Iron Hemosiderrin: insoluble, toxic form or iron that can form crystals

27.What are the two broad categories for being anemic? What is the definition of anemia? Know the general physiological consequences of anemia and understand their causes.

2 Broad Categories: Hemorrhagic and Hemolytic Consequences: Low blood viscosity-> Low resistance -> High blood return to heart-> High cardiac output Hypoxia-> Dilation of peripheral vessels-> High blood return to heart-> High cardiac output Short of breath: Low oxygen Fatigued: Low oxygen means low energy Chilly: poor blood circulation, no warmth

10.Know the result of osmosis and changes in volume when two solutions are separated by a membrane and (1) the two solutions have different osmolarities of a permeant solute, (2) the two solutions have different osmolarities of an impermeant/nonpermeant solute, (3) the two solutions have the same osmolarities.

???

10.What is an antigen presenting (APC) cell? What cell is a very powerful phagocyte?

APC: Antigen Presenting Cells, macrophage Monocyte: powerful phagocyte

42.Why does someone with Addison's disease show hyperpigmentation (understand the disrupted HPA pathway and know which hormones are elevated and which are decreased).

Addison's disease: pigmentation because ACTH stimulates melanocytes Hypothalamus (CRH), Pituitary (ACTH high), Adrenal (glucocorticoids low)

31.Addison's disease/primary hypoadrenalism: What is it? What could cause it? What hormonal profile would you expect in it? What are the signs and symptoms of the disease?Given that gland mass increases with increased stimulus and decreases with decreased stimulus, how would the mass of the adrenal gland be expected to change in this condition?

Addison's disease: primary hypoadrenalism, entire adrenal gland is destroyed due to injury, cancer, or autoimmune disorder (80% of cases), ACTH is increased, problem with adrenal gland Symptoms: Damaged adrenal cortex results in no aldosterone: Water/salt imbalance, plasma volume depletion (hypotension), hyperkalemia, metabolic acidosis; In addition: low blood glucose (hypoglycemia, from low cortisol), pigmentation (ACTH also stimulates melanocytes), decreased pubic /axillary hair in females (low androgens) AXIS: Hypothalamus, Pituitary, Adrenal Andrenal mass would decrease because glucocorticoids are decreased Profile: Hypothalamus (CRH)-> Pituitary(ACTH) -> Adrenal (glucocorticoids too low)

5.Know the differences in structure and affinity for oxygen among embryonic, fetal, and adult hemoglobin

Adult hemoglobin: HbA (a2b2) Males: 15-16 gm Hb/ 100 mL blood Females: 13-14 fm Hb/ 100 mL blood Embryonic: HbE (a2e2) Fetal: HbF (a2y2) O2 affinity: HbE> HbF> HbA

39.African pygmies: What causes it? What hormonal profile would you expect in it?

African pygmy- normal GH, but lack IGF-1 Profile: Hypothalamus (GHRH^, GHIHv)-> Pituitary (Growth Hormone)-> Liver(IGF-1, NO IGF-1)

12.Understand the role of albumin in maintain plasma osmolarity. Know that liver disease can affect albumin production and, hence, plasma osmolarity.

Albumin: synthesized by tryptophan Liver disease can affect albumin production and, hence, plasma osmolarity

7.How does water move? Which force is responsible for movement of water across capillaries and which is responsible for movement across cell membranes?

Always passive and unsaturable Two forces that drive water to move: Osmosis (osmotic pressure)- a chemical potential energy difference dependent on the water concentration on two sides of the membrane-Easier for physiologists to measure the solute concentration (more solute means less water; less solute means more water)- Driving force for water movement across CELL MEMBRANES Hydrostatic pressure- The pressure of the fluid exerted on the vessels, or container-Animal cell membranes are "flexible" so it is not a driving force across cell membranes-IT IS a driving force for moving plasma water across walls of CAPILLARIES

8.What hormones are synthesized by the amino acid, tyrosine?

Amines: hormones derived from tyrosine Ex: Dopamine (prolactin-inhibiting factor, PIF) - from hypothalamus Thyroid Hormone (TH, T3 + T4 )- from thyroid Norepinephrine / Epinephrine - from adrenal medulla

26.Know the different categories under which anemias are grouped.

Anemia: low oxygen carrying capacity from low hemoglobin concentration; either because of too fewRBCs or too little Hb in cells Blood Loss: Hemolytic or Hemorrhagic Defective RBC Production Hemolytic: can be Acquired or Inherited Acquired Hemolytic: transfusion incompatibility, venom, drugs Inherited Hemolytic: thalassemia, sickle cell, hereditary spherocytosis, G6PD deficiency Hemorrhagic: Acute or Chronic(leads to iron def.) Defective RBC Production: Iron Deficiency Aplastic Megaloblastic

4.Types and function/location of antibodies. Know the different classes of antibodies and their key characteristics.

Antibodies: immunoglobulins Y-shaped proteins, 2 long chains 2 short chains, linked by covalent bonds, Stem (Fc) region determines Ig class Arms (variable ends) are specific to the antigen they are meant to target. Usually 2, but more in large Ab's., V region recognize and bind to specific molecular epitopes IgG: 80% total, cross placenta, opsonization, neutralizes toxins and viruses IgA: body fluid, tears, bronchiole secretion, saliva, mucosa IgM: 10-15% total, first produced, especially effective against microorganisms and agglutinating antigens IgE: allergic reactions, histamine release, lysis of parasitic worms IgD: found on surface of B cells, activator for humoral response

21.What enzymes will aspirin and NSAIDs block? How are aspirin and NSAIDs different from each other? Why does low dosage aspirin work as an anti-platelet, but higher dosages can actually lead to more clot formation?

Aspirin & NSAIDS: block COX 1 enzyme Aspirin: irreversible cox inhibitor NSAIDS: reversible cox inhibitor Baby aspirin: prescribed to people with tendency to clot, only 81mg slight blood thinner

13.If a person has a bile duct obstruction (from a gall stone or portal hypertension), what clotting factors could they become deficient in? How can we help these individuals? Similarly, if a pet or child were to eat rat poison, what clotting factor(s) would they become deficient in and how should they be treated?

Bile duct obstruction: fat absorption problems, bile salts are needed to absorb fat, no vitamin K so deficient in factors II, VII, IX, X Vitamin K injection helps patients Rat poison is warfarin (anticoagulant): give patients Vit K to produce blood clotting

7.How can homeostasis be applied to body temperature?

Body temperature: normal 36-38° C This is the body's optimum temperature or set point

23.Know what causes bruises and why patients in anticoagulants may present more bruises than normal.

Bruises: without clotting, blood sits at trauma site and does not clot or dissolve, causes bruising

6.What prostaglandin is made by the endothelial cells to retard platelets from coming into contact with the cells and become activated?

COX-2

11.Describe centrifuged blood (the pellet (PCV), buffy coat and supernatant.)

Centrifuged blood: Erythrocytes are pulled to the bottom of the tube because they are denser than other blood elements PCV: ??? Buffy Coat: leukocytes and platelets, less than 1% of whole blood volume Supernatant: ???

2.What are the physical characteristics of blood? What are the functions of blood?

Characteristics of Blood: Adult ♂ contains 5-6L, Adult ♀ contains 4-5L Temperature: about 100.4° F 5 times as viscous as water-RBCs account for its viscosity pH ranges from 7.35 - 7.45 (slightly alkaline) Color ranges—oxygen poor (dark) vs. oxygen rich (light) Functions of Blood: Transportation-Gases, nutrients, hormones, wastes, antibodies. Regulation -Body fluid volume, Body fluid pH, Body temperature, Electrolyte levels Protection from pathogens and bleeding

17.How do we get clot removal? What is the role of plasminogen/ plasmin? On what does molecule does it act?

Clot removal: plasminogen gets trapped in clot, becomes proteolytic enzyme that busts the clot tPA activates plasminogen,

15.What is the role of platelets in clot retraction?

Clot retraction: actin and myosin filaments contract, then platelets contract and clot retraction occurs

10.Where are most clotting factors made?

Clotting factors: most made in the liver

8.What happens in the coagulation phase? What two pathways could be activated in the coagulation phase? How does the extrinsic pathway get activated? What about the intrinsic? Which one is faster? Slower? Which one generates more PAS? What are the steps of the common pathway?

Coagulation: clot formation, sequence of steps leading to conversion of fibrinogen to the insoluble protein fibrin, clot is a meshwork of fibrin fibers -requires calcium ions (factor IV), 11 factors synthesized by liver, proenzymes of zymogens, activation of some clotting factors (2,7,9,10) requires Vit. K Extrinsic pathway: triggered by damage outside the bloodstream, begins with release of tissue factor, quick to start, do not produce a lot of prothrombin, PAS Prothrombin Activator Intrinsic pathway: Contact activation, triggered by damage inside the bloodstream, release of platelet factor, tissue factor III from blood, takes longer to start, produces more PAS *Both pathways start simultaneously and converge at one final common pathway Common pathway: Extrinsic and Intrinsic Pathway -> PAS -> Fibrin Polymers(final common pathway)

9.What are the components of RBCs? That is, what are they made of? What is hemoglobin? What is a normal blood Hb concentration value? What is heme? What are globin chains? Are there different globin chains expressed throughout life? IF so, which ones and when? Describe their relative affinities for oxygen.

Components: Mean Corpuscular Volume (MCV)-MCV 80-100 μm3 Mean Corpuscular Hemoglobin (MCH)-32μμg (10-12; picogram)-Weight of Hb in a single RBC Mean Corpuscular Hemoglobin Concentration(MCHC)-34%-Concentration of Hb to volume in a single RBC (i.e., solute/solvent). Mean Corpuscular Diameter (MCD)-MCD 7-8 μm Color Index (CI)-CI 0.9 - 1.1 Hemoglobin Normal Concentration: 15g%/100mL blood Heme: 4 in each hemoglobin, porphyrin ring + iron, iron ion in heme is able to reversibly bind an oxygen molecule Globin Chains: determine Hb's affinity for oxygen (allow loading and reloading of O2), 2 alpha chains and 2 beta chains Embryonic globin chains (HbE)A2E2, Fetal globin chains (HbF) A2Y2, Adult globin chains (HbA) A2B2

43.Congenital adrenal hyperplasia: What is it? What causes it? What are the signs and symptoms?

Congenital Adrenal Hyperplasia: autosomal recessive trait, deficiency of any of the five enzymes necessary for cortisol production Increase ACTH Hypothalamus (CRH), Pituitary (ACTH high), Adrenal (glucocorticoids high) Mineralcorticoids (aldosterone) may be excessive or deficient Diagnosed at birth: females have virilization, enlarged clitoris, fused labia; males rarely diagnosed With treatment (give patient cortisol throughout whole life) and surgery, sex characteristics and fertility becomes normal

20.What are the possible costs and benefits of fever? Can a fever be a good thing? Why? What is the current hypothesis about a low-grade fever and how it can be "protective."What is the "principle of asymmetric harm"?

Costs of fever: High metabolic rate is particularly demanding during physiological stress (infections) Fever may exacerbate tissue damage associated with aspects of immune response Fever may harm growth of microorganisms Benefits of fever: Fever may speed up immune defense Fever may also increase the expression of heat shock proteins, which are useful in repairing cells from damages A fever can be a good thing because it fights off macrophages to rid the body of infection Low grade fever: ??? Principle of asymmetric harm: failing to initiate a defense response when it is needed tends to be vastly more harmful than needlessly invoking a defense response when it is unnecessary (e.g. "smoke detector analogy")

29.Cretinism: What causes it?

Cretinism: mental defects due to maternal iodine deficiency

32.Cushing's disease: What is it? What could cause it? What hormonal profile would you expect in it? What are the signs and symptoms of the disease?Given that gland mass increases with increased stimulus and decreases with decreased stimulus, how would the mass of the adrenal gland be expected to change in this condition?

Cushing's Disease: (secondary hypercortisolism) Pituitary tumor, excess ACTH, high cortisol, problem with pituitary gland Symptoms: same as cushing's syndrome, add a tumor Pituitary mass would increase because ACTH is increased Profile: Hypothalamus (CRH)-> Pituitary(ACTH too high) -> Adrenal (glucocorticoids)

33.Cushing's syndrome/primary hyperadrenalism: What is it? What could cause it? What hormonal profile would you expect in it? What are the signs and symptoms of the disease?Given that gland mass increases with increased stimulus and decreases with decreased stimulus, how would the mass of the adrenal gland be expected to change in this condition?Know the hormone profile of iatrogenic (physician-induced) Cushing's syndrome.

Cushing's Syndrome: (primary hypercortisolism) iatrogenic(physician induced), exogenous source of cortisol, all adrenocortical hormones elevated Symptoms: buffalo hump, moon face, muscle loss, striae, hyperglycemia, immune suppression, problem with adrenal gland Adrenal mass would increase because glucocorticoids increase Profile: Hypothalamus (CRH)-> Pituitary(ACTH) -> Adrenal (glucocorticoids too high)

1.Be able to explain how information is converted from DNA into proteins.Where does transcription occur? Where, in the cell, does it happen?What material does it begin with and what material is created when finished?

DNA -> RNA -> PROTEIN Transcription: occurs in the nucleus of a cell, making a "working copy" of a gene DNA ->(transcription) -> RNA -> PROTEIN Material begin with: DNA Material created: RNA

12.What are the mechanisms to decrease body temperature? Know the different physiological responses that follow a change inbody temperatureabove set point as our body attempts to return to set point.

Decrease body temp: increased heat loss, vasodilation transfers heat to skin, sweating (evaporative water loss), sprawled position, less movement

26.Know what causes deep vein thrombosis and its possible consequences.

Deep Vein Thrombosis: blood clot forms in deep vein, could break off and go into blood stream and cause an embolus

21.What would happen if there was a defective hormone or a defective receptor for the hormone in terms of homeostasis? How would this affect circulating levels of all the other hormones in the axis? Be able to identify examples of negative and positive feedback regulation in hormonal axes.

Defective hormone- leads to hormonal imbalance Other hormones- would increase their secretion to make up for defective hormone

6.With respect to hematopoiesis, what can you say about a cell that is determined vs. a cell that is differentiated?

Determined: the fate of the cell Differentiated: morphological modification of the cell to preform assigned function

30.Diabetes mellitus: What causes it? What are its effects on plasma glucose levels?

Diabetes mellitus: diet is main cause, solute concentration of sugars increase in plasma, osmotic pressure increases, water leaves cells to go to plasma

11.Regarding the diabetes question from class, why does an excessive blood sugar level cause dehydration at the cellular level?

Diabetes: Elevated blood sugar levels; sugar does not move easily to cells Relatively less water due to increased solute concentration Person eventually becomes dehydrated at the cellular level, thirst center in the hypothalamus is activated (polydipsia: excessive thirst)

13.Know that one cause of edema is difference in osmolarity across body fluid compartments

Edema caused by low plasma protein Fluid moves from plasma into the interstitial space (seemingly increased concentration) and then into an area of low resistance (the peritoneal cavity - ascites) Failure to grow, lethargy, depressed mentality

4.Where does erythropoiesis occur throughout the stages of life? Know where, in the body, hematopoiesis takes place during different stages of embryonic and fetal development and after birth.

Erythropoiesis: 5-7 days Stages of Life: Embryonic: yolk sac Fetal: liver and spleen After birth: bone marrow Adult: axial skeleton

7.Understand the lineage of erythropoiesis. When do RBCs enter the blood stream? Are they mature as they enter? What percentage of RBC's are normally reticulocytes? How do reticulocytes differ in appearance from mature RBC's? What is the significance of an elevated reticulocyte count? Understand blood cell production in the bone marrow and the role of hemocytoblasts.

Erythropoiesis: the production of red blood cells When do RBCs enter the blood stream: start off as reticulocytes and turn into erythrocytes Not mature as they enter, reticulocyte is not mature (been in blood stream 1-2 days) Erythrocyte is mature and differentiated 1% of RBCs are reticulocytes Erythrocytes have biconcave disc, reticulocytes do not Elevated Reticulocyte count: more RBCs means more oxygen, higher endurance Blood cell production in bone marrow: Hemocytoblast (multipotent stem cell) -> Myeloid Stem Cell-> Proerythroblast-> Basophil erythroblast-> Polychromatophil erythroblast-> Orthrochromatic erythroblast-> Reticulocyte-> Erythrocyte

25.What disorders arise when there is excessive RBC production? How do we treat primary/secondary Polycythemia?

Excessive RBC Production: Polycythemia Polycythemia vera (primary): treated by blood let and adding isotonic saline Secondary Polycythemia: treated by blood let and isotonic saline, low flow oxygen if respiratory disorder

22.How might an excess of an exogenous hormone (someone "taking hormones") like cortisol, or birth control pills, or thyroid extract affect release of "endogenous" hormone? Think about your negative feedback mechanisms! What could happen to someone who is on cortisol for long-term and then immediately stops taking their medication?Know how endogenous levels of hormones of an HPX axis would change when exogenous source of one of the hormones is given to a patient. Be able to predict how the size of HPX glands would change as a result of therapy with exogenous cortisol, sex hormones, growth hormone, or thyroid hormone.

Exogenous vs. Endogenous hormone- the exogenous hormone would replace the endogenous hormones so the endogenous hormone would decrease its secretion because of the exogenous hormone Exogenous cortisol- if they stopped taking cortisol, they would not be producing enough internally, causes Secondary Adrenal Insufficiency: Aldosterone levels tend to be closer to normal (in comparison to Addison's disease): no hyperkalemia, no hypotension ACTH levels are low: no hyperpigmentation (melanocytes are not stimulated) Glucocorticoids are low: hypoglycemia, sluggishness of energy mobilization, high susceptibility to infections Size of HPX glands: Exogenous cortisol: endogenous productions will go down, size goes down (shrinks over time) Sex hormones: endogenous productions will go down, size goes down (shrinks over time) Growth hormones: endogenous productions will go down, size goes down (shrinks over time) Thyroid hormone: endogenous productions will go down, size goes down (shrinks over time)

14.What is the action of factor XIII (fibrin stabilizing factor)? How does it work?

Factor XIII: comes mostly from platelets, strengthens fibrin reticulum (clot formation), it links fibrin monomers

14.What are the "fates of hormones"?What could happen to a hormone after its release? Know that hydrophobic hormones have a longer half-life than hydrophilic hormones, and why.Understand the use of the term "clearance"or "clearance rate". Know that the liver is involved in the clearance of hormones.Understand that hormones are not attached to receptors on their target cells for a long time.

Fates of Hormones: -degraded in blood stream' -may be activated T4-T3 -may be excreted by kidneys/liver -may reach a target cell and cause a response -may need carrier to reach target cell Hydrophobic hormones have a longer half-life than hydrophilic hormones Clearance rate: liver is involved in clearance of hormones

14.Be able to describe the course of fever and its associated physiological responses. How does our body increase its temperature?What does it mean to say that a fever "broke"? What are the physiological changes that happen when a fever has "broken"? How does our body increase its temperature?How does a fever re-set the set point? What is cyclooxygenase? How can this enzyme's activity lead to a fever? How can we stop this enzyme's activity? What are NSAIDS?

Fever/ hyperexia: elevated core temperature reflects resetting the temperature set-point Pyrogens: cause set point of hypothalamic thermostat to rise Cytokines: polypeptides release by macrophages and lymphocytes following phagocytosis of bacteria Fever broke: temperature returning to set point Return to set point: ??? Cylooxygenase: enzyme that cleaves arachidonic acid and generates E2 prostaglandin, can generate fever because PGE2 causes the hypothalamus to elevate the set point Antipyretics, Cox enzymes: inhibit PGE2 from producing fever NSAIDS: Non-Steroidal Anti-Inflammatory Drugs, types of antipyretics

15.When the posterior hypothalamus alters set point, what do we now call the current body temperature?What compensation occurs to cause the body temperature to reach this new set point? Be sure you can explain the reverse when "crisis" occurs.

Fever: when set point is elevated by hypothalamus and body temperature is raised Pyrogens: cause set point of hypothalamic thermostat to rise cytokines: polypeptides released by macrophages and lymphocytes following phagocytosis of bacteria Interleukin 1 (IL-1) is a cytokine released from macrophages IL-1 raises set-point by interacting with a "leaky" portion of the blood-brain barrier that lies on the wall of the third ventricle (above the optic chiasma) IL-1 causes endothelial cells to increase prostaglandin production (mainly PGE2) from arachidonic acid PGE2 causes the hypothalamus to elevate the temperature set-point Crisis: when the fever breaks and the body begins to return to its normal set point

4.If all nucleated cells have the same DNA in our body, then why does heart tissue look and behave like a heart and bone looks and behaves like bone?

Gene expression: the final end result is the synthesis of a protein, the physiology comes from the protein functions Each protein has a different function that causes different parts of the body to function differently

41.Gigantism: What causes it? What hormonal profile would you expect in it?

Gigantism: excess growth hormone in prepuberty, usually caused by a tumor of the pituitary that grows until whole gland is destroyed Hypothalamus (GHRH^,GHIHv), Pituitary (Growth hormone too high), Liver (IGF-1)

7.Know what glucocorticoids and mineralocorticoids are, including the main example of each category.

Glucocorticoids: Cortisol - secreted in response to ACTH. It stimulates fat and protein catabolism, gluconeogenesis (generation of glucose from non-carbohydrates; i.e. increases blood glucose levels) and reduces rate of glucose utilization. Also blocks inflammatory process and helps resist stress Mineralocorticoids: Aldosterone - Sodium/water are reabsorbed and potassium is lost

28.Know the type of problems on the HPT axis that could cause a goiter.

Goiter: caused by under or over secretion of TSI or TSH, can be caused by hyperthyroidism or hypothyroidism

2.Know which leukocytes are granulocytes and which are agranulocytes

Granulocytes: eosinophils, basophils, neutrophils Agranulocytes: monocytes, lymphocytes

23.Review the diseases and the problems with the axial relationships: Grave's disease, Hashimoto's hypothyroidism, Iodide deficiency, Cushing's disease, Cushing's Syndrome, secondary hypoadrenalism, and Addison's disease. Be ready to identify these diseased states based on description of patient signs and symptoms. Know their disrupted pathways and levels of hormones.

Grave's disease: problem with thyroid gland Hashimotos: problem with thyroid gland Iodide Deficiency: problem with thyroid gland Cushing's Disease: problem with pituitary gland Cushing's Syndrome: problem with adrenal gland Addison's disease: problem with adrenal gland Secondary hypoadrenalism: Deficiency of ACTH, problem with the pituitary, more common than Addison's disease, rapid withdrawal of pharmacologic doses of cortisol

24.Graves' disease: What is it? What could cause it? What hormonal profile would you expect in it? What are the signs and symptoms of the disease?Given that gland mass increases with increased stimulus and decreases with decreased stimulus, how would the mass of the thyroid gland be expected to change in this condition?

Graves disease: Thyroid-stimulating immunoglobulins (TSIs) form against the TSH receptor in the thyroid gland; most common form of hyperthyroidism, thyroid gland stimulates too much TH AXIS: Hypothalamus, Pituitary, Thyroid Thyroid mass would increase, because thyroid hormone stimulus is increased Profile: Hypothalamus (TRH)-> Pituitary(TSH) -> Thyroid (TH too high)

17.Know all glands and hormones (including all variations of their names discussed in class) of the HPT, HPA, and HPL axes. Know the following information for these hormones: TH, Cortisol, aldosterone, Growth Hormone and parathyroid hormone, TRH, TSH (there are a lot of actions for this one—KNOW THEM: look at your textbook), CRH, ACTH, insulin, and glucagon.•Where it is made •Where is its target organ (cell),•what the target organ/cell would do (the effect), •and what mechanism stimulates the hormone release? (hormonal, humoral, or neural).•Know the specific physiology, regulation of, and feedback mechanisms of the hormone •Which of these hormones does not have an "axis?" Why? In other words, how is its release controlled? Does aldosterone TRULY follow an axial relationship? What about cortisol?

HPT: Hypothalamus, Pituitary, Thyroid HPA: Hypothalamus, Pituitary, Adrenal HPL: Hypothalamus, Pituitary, Liver Thyroid Hormone: (TH,T3,T4), from thyroid, amine-derived, goes all the way to the nucleus binds to nuclear receptor and has direct effects on DNA transcription, results in new protein synthesis, target cell: all body cells Cortisol: steroid, from adrenal cortex, glucocorticoid, secreted in response to ACTH, stimulates fat and protein catabolism, gluconeogenesis, reduces rate of glucose utilization, blocks inflammatory process, reduce stress, HPA axis, Prednisone is synthetic form Aldosterone: Growth Hormone: Parathyroid Hormone: TRH: TSH: CRH: ACTH: Insulin: Glucagon:

3.Is there homeostasis in the hemostatic balance? That is, is there a balance between clotting factors and anti-coagulants?

Haemostatic balance: Procoagulants and platelets -> Thrombosis; Natural anticoagulants -> Bleeding, Not clotting

25.Hashimoto's disease: What is it? What could cause it? What hormonal profile would you expect in it? What are the signs and symptoms of the disease?Given that gland mass increases with increased stimulus and decreases with decreased stimulus, how would the mass of the thyroid gland be expected to change in this condition?

Hashimotos: autoimmune disease causing chronic inflammation and consequential failure of the thyroid gland, thyroid gland does not produce enough TH Symptoms: pale skin, puffy face, weight gain AXIS: Hypothalamus, Pituitary, Thyroid Thyroid mass would decrease, because thyroid stimulating hormone is decreased Profile: Hypothalamus (TRH)-> Pituitary(TSH) -> Thyroid (TH too low)

15.Define each of the following terms (not just the names of the initials!) and give normal values for each of the following: Hb concentration, MCHC, MCH, MCV, MCD, and CI. Know the units for each (as applicable)!

Hb concentrations: weight of Hb in 100mL blood, normal value is 15g%/100mL blood MCHC: Mean Corpuscular Hemoglobin Concentration, 34%, concentration of Hb in a single RBC MCH: Mean Corpuscular Hemoglobin, 32uug(picogram), weight of Hb in a single RBC MCV: Mean Corpuscular Volume, MCH 80-100um^3 MCD: Mean Corpuscular Diameter, 7-8um CI: Color Index, 0.9-1.1

13.Define hematocrit. Give normal value ranges for male and female. List some examples of conditions in which these values might increase or decrease.

Hematocrit: % volume of blood that is RBCs Male: 42-52% HCT Female: 37-47% HCT Polycythemia: an elevated hematocrit

6.What are the different types of stem cells? Which kind is the hemocytoblast? Which kind is the zygote? Understand the difference of determination vs. differentiation as the formed elements are synthesized in red marrow.

Hematopoiesis: precursor of all blood cells, determined not differentiated Totipotent - zygote Pluripotent - a stem cell that has the potential to differentiate into ectoderm, mesoderm, or endoderm cells Multipotent - a stem cell that has the potential to give rise to a limited number of lineages, hemocytoblast, determined Unipotent - a stem cell that can generate only one differentiated cell type; generates from a multipotent cell

5.With respect to the hemocytoblast, as learned in your erythropoiesis lecture, is it a pluripotent, multi-potent, or unipotent stem cell?

Hemocytoblast- multipotent

25.What is hemophilia? Understand the specific causes and consequences of the three different types of hemophilia discussed in class. Discuss its mode of genetic transmission with regard to factors VIII and IX. What is meant by the term "carrier?" If a hemophiliac lacks factor IX, can an injection of vit. K help them?Know which ones are sex-linked and the consequence of this form of inheritance to male and female offspring.

Hemophilia A: lack of factor VIII, X linked Haemophilia B: lack of factor IX, X linked Von Willebrand Disease: plasma protein that carries factor VIII Symptoms: lots of bleeding Carrier: inherited, X gene

2.What are the major steps in the overall process of hemostasis?Differentiate between plug formation and coagulation (clot formation.) Are they the same?

Hemostasis: prevents blood loss through the walls of damaged blood vessels and establishes a framework for further tissue repairs 1. Vasoconstriction: myogenic contraction of smooth muscle, local myeogenic spasm, local factors, thromboxane A2 release, nervous reflexes 2. Platelet phase: glycoproteins on platelets adhere to injured areas, esp exposed collagen fibers, release ADP and thromboxane A2 to activate nearby platelets -platelets- swell, irregular space, granular contents, become sticky, attach to collagen fibers and von willebrand factor (vWF), positive feedback: platelet plug, NOT a clot 3. Coagulation: clot formation, sequence of steps leading to conversion of fibrinogen to the insoluble protein fibrin, clot is a meshwork of fibrin fibers -requires calcium ions (factor IV), 11 factors synthesized by liver, proenzymes of zymogens, activation of some clotting factors (2,7,9,10) requires Vit. K 4. Clot retraction: RBCs and platelets stick to fibrin strands, clot retraction (20-60 mins), actin and myosin filaments contract, pulls torn edges of the vessel closer together, platelet releases growth factor 5. Clot dissolution: plasminogen trapped in clot, when activated becomes proteolytic enzyme, plasmin is clot buster, Tissue Plasminogen Activator, Thrombin factor II negative feedback- fibrinogen creates clot, plasminogen dissolves clot

Thrombocytes and Hemostasis (notice, not "homeostasis")

Hemostasis: stopping the flow of blood

18.Know the effects of heparin, protamine, calcium chelators (citrate, oxalate, EDTA, EGTA), aspirin, and coumadin/coumarin/warfarin on clotting times and understand their mechanism of action.How do they differ in their mechanism of action? Which ones will immediately halt coagulation if added to blood in a test tube?

Heparin: released by mast cells and basophils, also given as drug, anticoagulant, works instantly Protamine: binds to heparin and removes it from circulation Calcium chelators: bind to calcium and/or change its ionic form Citrate: deionizes calcium, can be infused back into patient Oxalate: forms calcium precipitate, cannot be diffused back into patient EDTA,EGTA: bind to calcium and change its ionic form Aspirin: irreversible COX enzyme inhibitor, blocks formation of thromboxane A2, formation of platelet plug less likely Coumadin/Coumarin/Warfarin: natural substance found in plants, rat poison, blocks enzyme that activates Vit K, so there is no clotting, cannot prevent coagulation in a blood sample

5.Know the role of histamine and heparin and which leukocytes releases them.

Histamine: vasodilator and increase capillary permeability Heparin: Anti coagulant

1.Define homeostasis. What is the ultimate goal in homeostasis? If we didn't have homeostasis, what would happen to cells and proteins? Know that most capillaries are less than 50 micrometers (microns) to most cells of the body.

Homeostasis: the maintenance of a stable milieu interieur (internal environment) Ultimate goal: prevent denaturing of proteins, to keep cells under optimum conditions for function and survival Capillaries: < 50 um

16.Understand the anatomy and physiology of the pituitary gland, including the hormones it produces(anterior) and stores(posterior)and their target cells. Understand the communication of the anterior pituitary(adenohypophysis) and of the posterior pituitary(neurohypophysis) with the hypothalamus, and why they are different.

Hormonal control: Hypothalamus releases many different hormones that will trigger the anterior pituitary to, in turn, release hormones that target different organs Hormones released by the anterior pituitary: Melanocyte-stimulating Hormone (MSH)Growth hormone (GH)Adrenocorticotropic Hormone (ACTH)Prolactin (PRL)Thyroid-stimulating Hormone (TSH)Luteinizing Hormone (LH)Follicle-stimulating Hormone (FSH) •Anterior pituitary does produce and release its own hormones in response to hypothalamic input, thyroid stimulating hormone •Posterior pituitary is, in fact, an extension of the hypothalamus and does not make hormones, oxytocin, ADH

2.What are the basic hormone actions? How do hormones ULTIMATELY change cell activity?

Hormones: chemicals released by glands in the blood -circulates body -only effect target cells -effects depend on target cell Ultimately alter cell activity: by altering protein activity through gene expression or through altering phosphorylation

11.What is humoral immunity? Which cells are responsible for it?What cells secrete antibodies?

Humoral immunity: effective against pathogens outside the cell, in circulation B cells: responsible, antibody secretion

9.Humoral vs. cell-mediated response: what cells are involved? What cell type unites these two divisions of the immune response?

Humoral: B lymphocytes -effective against pathogens in circulation or outside the cell -when activated, become plasma cells, produce antibodies -antibodies bind to antigen -secondary/memory response produce Abs Cell mediated: T lymphocytes -act over short range -interact w another cell in body -can kill/signal other cells\ -only recognize antigen on surface of target cell -Cytotoxic Cells: kill infected cells -Helper Cells (two types): activate macrophages and B-cells -Suppressor Cells: regulate activity

11.How are hydrophobic hormones transported in the blood? How do the different classes of hormones communicate with their target cells/organs—that is which ones can enter the cell and which ones can't? IF a hormone can't enter the cell, how does the cell respond to the hormone? What changes to the cell do the different classes of hormones cause in their target cells (i.e., what effects are caused in the target cells). What determines whether a hormone will bind a membrane receptor or an intracellular receptor? Given a hormone, be capable of knowing its category, basic properties (hydrophobic/hydrophilic), whether they require a transport (carrier) protein in the plasma, where its receptors can be found, and whether they use a second-messenger system.

Hydrophobic (lipophilic): Require a transport protein to be carried in bloodstream, long lasting effects, not easily cleared; dissolve in body fat stores, have long "half life", can "go all the way" across cell and nuclear membranes to bind receptor, act directly on gene transcription Ex: Steroids, thyroid hormone Hydrophilic (lipophobic): may not require a transport, usually soluble in water, must bind receptor on the target cell membrane and trigger second messengers (e.g. cAMP, DAG+IP3) to change physiology of target cell Ex: Peptides, Amines (NOT Thyroid Hormone)

44.Why does an infant with congenital adrenal hyperplasia show hyperpigmentation and fused labia majora? What is wrong with the adrenal cortex? How can we help the baby? What will she (and a boy baby born with this) need in terms of hormone therapy?

Hyperpigmentation: increased ACTH stimulates melanocytes Labia Majora: fused because of overstimulation of mineralcorticoids Adrenal cortex: stimulates too many or too little glucocorticoids Help the baby: give cortisol, surgeries Hormone therapy: decrease ACTH and adjust glucocorticoids

13.Know the different changes in body temperature and thermoregulation that occur during exercise

Hyperthermia: prolonged exposure to heat and humidity, can cause heat stroke exercise induced hyperthermia- from the initial imbalance between heat production and heat loss, NOT from a change in set point Hypothermia: prolonged immersion in cold water, could stop heart

9.What will happen to a cell / to the cell volume if it is placed in a hypertonic solution? What if It is placed in a hypotonic solution? What if it is placed in an Isotonic solution?

Hypertonic: cell shrinks Hypotonic: cell swells Isotonic: cell stays the same

5.Do they have the same overall concentration of particles per unit of volume? If not, what will happen? Review hyper/hypo osmolality and crenation and swelling.

Hypo osmotic: lower osmolarity compared to surrounding solution, lower osmolarity than body fluids Hyper osmotic: higher osmolarity compared to surrounding solution, higher osmolarity than body fluids

17.What alters the hypothalamic set point? Under what conditions can hypothalamic set point be altered?Does exercise? Review your fever and exercise graphs we covered in class. What drugs have you learned that alter the set point when you have a fever?

Hypothalamic set point: altered by prostaglandin (PGE2) Conditions: Gram - bacilli, viruses, fungi, endotoxins, antigen/antibody reactions Exercise: does NOT alter set point Antipyrectics/ Cox inhibitors: NSAIDS bring temperature down

34.Be able to determine hormonal profiles for HPX hormones under conditions of over-and under-secreting tumors for each gland of the hormonal axis. Given that gland mass increases with increased stimulus and decreases with decreased stimulus, how would the mass of the glands involved be expected to change in each condition?Be able to determine the source of a problem (i.e.,which gland is over-or under-secreting) after being given a hormone profile.

Hypothalamus (TRH)-> Pituitary(TSH) -> Thyroid (TH) Hypothalamus (CRH)-> Pituitary(ACTH) -> Adrenal (Glucocorticoids) Hypothalamus (GHRHsomatotropin^, GHIHsomatostatinv)-> Pituitary (Growth Hormone)-> Liver(IGF-1) Hypothalamus (Gonadotropin Releasing Hormone GmRH) -> Pituitary (Leutinizing Hormone LH, Follicle Stimulating Hormone FSH) -> Gonads (testosterone, estrogen, progesterone)

11.What are the mechanisms to increase body temperature?Know the different physiological responses that follow a change in body temperature below set point as our body attempts to return to set point.

Increase body temp: reduced heat loss, vasoconstriction impedes heat transfer to skin (stays at core), fetal position , shivering

18.Understand the processes involved in the maintenance of homeostatic balance of erythropoiesis. What conditions lead to increased or decreased EPO levels? Where is EPO secreted from? What are its effects?

Increased EPO: Polycythemia Decreased EPO: Anemia EPO: secreted 90% in the kidney, 10% in the liver EPO: Promotes release of reticulocytes Stimulates stem cell mitosis Increase in red cell number in 5 days Synthetic EPO /Recombinant Human EPO—"Ecrit", "Eprex", "Dynepo"

7.What happens during an inflammatory response? Is it a form a specific or non-specific defense?

Inflammatory Response (NON SPECIFIC) : 1. Tissue damage 2. Chemical change in interstitial fluid 3. Mast cells release histamine and heparin 4. Dilation of blood vessels, increase blood flow, increased vessel permeability 5. Area becomes red, swollen, warm, and painful 5. Clot formation 6. Attraction of phagocytes, esp neutrophils 7. Activation of specific defenses 8. Removal of debris by neutrophils and macrophages 9. Tissue repair

8.What are the components of the innate immune system?

Innate Immune System: ???

2.What compartments do we find this water? Are they the same volume? Order them from largest to smallest. Do they have the same composition?

Intracellular Fluid (30-40% of body weight) Extracellular Fluid-Interstitial fluid(the water immediately outside cells, between and around cells; 15%) Plasma fluid(the water inside blood vessels, but not in blood cells; 4-5%) Transcellular fluid(the water enclosed in chambers lined by epithelial membranes; e.g. synovial, peritoneal, pericardial, and intraocular spaces, as well as the cerebrospinal fluid; 1-3%)

26.Iodide deficiency: What hormonal profile (in the HPT axis) would you expect? Why? Given that gland mass increases with increased stimulus and decreases with decreased stimulus, how would the mass of the thyroid gland be expected to change in this condition?

Iodide Deficiency: increase TRH and TSH, not enough TH, defective thyroid gland AXIS: Hypothalamus, Pituitary, Thyroid Thyroid mass would decrease, because thyroid stimulating hormone is decreased Profile: Hypothalamus (TRH)-> Pituitary(TSH) -> Thyroid (TH too high)

23.Know which iron form is required for a functional hemoglobin molecule(ferrous or ferric ion), what happens when iron is oxidized, and the type of anemia that results in methemoglobin production.

Iron 2+: ferrous, required for a functional hemoglobin molecule Iron 3+: ferric, oxidized, cannot bind oxygen, forms methemoglobin Anemia: G6PD, from methemoglobin production

28.Know the expected MCV. MCH, and MCHC levels (normal, higher than normal, or lower than normal) for all types of anemia discussed in our lecture. Know how to describe these values using the terminology for chromasia, anisocytosis, poikilocytosis. Make sure you understand the relationship of MCHC= MCH/ MCV for each of the anemias

Iron deficiency: low MCH, low MCV, low MCHC Aplastic: cannot use MCH, MCV, MCHC because RBCs not produced Megaloblastic: high MCH, high, MCV, normal MCHC Hemorrhagic (acute and chronic): normal MCH, normal MCV, normal MCHC Acquired Hemolytic: normal MCH, normal MCV, normal MCHC Thalassemia: low MCH, low MCV, low MCHC Sickle cell: normal MCH, normal MCV, normal MCHC Hereditary Spherocytosis: normal MCH, low MCV, high MCHC Chromasia: MCH, hyperchromic, hypochromic, or normochromic Anisocytosis: MCV, microcytic, macrocytic/megalocytic, normocytic Poikilyocytosis: Abnormal shape, sickle cell, spherocytosis, echinocyte, pokilocytic MCHC = MCH/MCV

10.What is iron? What state of iron can bind oxygen? Why can't we use just iron for oxygen transport?Describe the physical characteristics of RBCs: why are they shaped the way they are? Know the molecular composition of hemoglobin, the importance of its components, and that, as any protein, it tends to change shape (and become less efficient) under non-optimal pH and temperature environments. How many oxygen molecules can a single hemoglobin molecule carry when it is fully loaded with oxygen?Where, in the molecule, do these molecules bind?

Iron: Free iron in the intestines combine with protein apotransferrin to make transferrin -> Transferrin is released into the blood to form plasma transferrin-> plasma transferrin delivers iron to iron deficient cells-> In the cytoplasm, iron combines with apoferritin to form ferritin (storage iron)-> if apoferritin cannot combine with all iron available, iron will be stored in the insoluble, toxic form hemosiderin Hemoglobin normally binds to iron in ferrous (reduced; +2) form, which binds indirectly to oxygen (forming oxyhemoglobin) In some cases, Hb binds to iron in ferric (oxidized; +3) form, which cannot bind oxygen (forming methemoglobin) RBCs: Biconcave disc- provides a large surface area for O2entry/exit Enables them to bend and flex when entering small capillaries Membranous bags of hemoglobin, a protein found in extreme abundance in RBCs, which binds and transports O2 and CO2 Hemoglobin: 4 polypeptides: 2 a chains, 2 b chains a & b chains synthesized at ribosome in the cytoplasm, porphyrin rings bind in to them in cytoplasm and form Hb Protein found in RBCs Tends to change shape (and become less efficient) under non-optimal pH and temperature environments 4 heme means 4 O2 molecules Iron ion in heme is able to reversibly bind an oxygen molecule

24.What is jaundice? What would happen to the breakdown products of hemoglobin (heme) if there is liver failure? If there is a bile duct blockage? That is, which types of bilirubin would accumulate and cause jaundice. What types would accumulate if an alcoholic has cirrhosis of the liver and hepatic portal tension?Know the causes and consequences of obstructive and hemolytic jaundice.

Jaundice: Hemolytic Jaundice: Free UNCONJUGATED bilirubin levels rise, RBCs are hemolyzed more quickly than hepatocytes can conjugate Obstructive Jaundice: CONJUGATED bilirubin due to clogged bile ducts, rate of bilirubin formation is normal, but cannot pass from blood to intestines, feces can be clay colored Liver failure: Bilirubin remains unconjugated and cannot pass through blood into feces or bile Bile duct blockage: Bilirubin is conjugated but cannot pass through feces because of blockage Alocholic has Cirrhosis of liver: bilirubin cannot conjugate and cannot pass thru blood into feces or bile

14.What causes Kwashiorkor?Understand the fluid compartments affected by Kwashiorkor.

Kwashiorkor - "disease of deposed child" (no longer suckled), swollen and distended belly Corn has no tryptophan (needed to synthesize albumin and other proteins) In economically disadvantaged countries, cornmeal is used to feed children at home, hospitals and nursing homes Fluid compartments affected: fluid in interstitial space increases, and fluid in the peritoneal cavity increases because it's and area of low resistance

38.Laron Dwarfs: What causes it? What hormonal profile would you expect in it?

Laron dwarfs- lack GHBP (GH binding protein)-300 worldwide-33% in Ecuador Profile: Hypothalamus (GHRH^, GHIHv)-> Pituitary (Growth Hormone)-> Liver(IGF-1, too low/ not receptive)

3.Know where leukocytes are formed

Leukocytes: formed in bone marrow

12.Disorders of immune system: leukocytosis/ leukemia/ leucopenia/ HIV/ autoimmune disorders-be sure you know what these terms mean, and their main characteristics as explained in the lecture.

Leukocytosis: excessive number of WBCs, -modest number normal during infection -extreme >100,000 indicates leukemia Leukemia: malignant disease of the blood forming tissue Lymphocytic leukemia: in lymphoid cells Myelogenous leukemia: cancer in bone marrow -poorly differentiated cells dont function properly -interfere with maturation of normal blood cells -consequent anemia and poor clotting, bleeding -bone medullary expansion, fragile easy broken bones -loss of nutrients from excessive mitosis -cells ineffective (immature) Leukopenia: low numbers of WBCs -causes infection -from radiation, drug use Autoimmune disorders: Excessive: hypersensitivities- allergies, autoimmunity Diminished: immune deficiency- HIV/AIDS

1.Types, abundance, and function of the white blood cells. Be able to place all leukocytes in order from the most numerous to the least numerous.Know the different leukocytes and know the key functions / characteristics of each type of leukocyte

Leuokocytes: white blood cells 60%,30%,6%,3%,1% Neutrophils: 60%, most abundant, very mobile, second to arrive at injury site, phagocytic/opponization Lymphocytes: 30%, T or B, react to one specific antigen, when activated they rapidly duplicate, some workers some memory T lymphocytes: cell mediated immunity, act over short range, can kill/signal other cells Cytoxic T cells: kill infected cells Helper T cells: activate macrophages and B cells Suppresser cells: regulate activity B lymphocytes: humoral immunity, pathogens outside the cell, become plasma cells, speifically bind to antigens, retain memory Monocytes: 6%, differentiates into tissue macrophage, first to arrive at injury site, phagocytic/opponization Eosinophils: 3%, main method of attack is exocytosis of target compounds on surface of target, defends against parasites like flukes or parasitic worms, increase in parasitic infection Basophils: 1%, enhance local inflammation, IgE binds to allergen and stick to basophil, release histamine and heparin

15.Kwashiokor/ alcoholism—why does a decrease in albumin lead to the ascites? Explain your answer with respect to water shifting from one compartment to the next; i.e. understand osmosis and why water moves out of the plasma in Kwashiorkor.

Low plasma protein (albumin, because no tryptophan). Fluid moves from plasma into the interstitial space (seemingly increased concentration) and then into an area of low resistance (the peritoneal cavity - ascites)

7.What factors can activate platelets? What do platelets look like when activated? What important chemicals are contained within platelets? How do platelets form a plug (include descriptions of collagen and vW factor).

Megakaryocytes: produce platelets in bone marrow Platelets when activated: swell, pseudopods, granule contents, become sticky Von Willebrand Factor (vWF): glycoprotein that arrives at tissues from plasma, platelets attach to vWF and collagen fibers to form platelet plug Platelet plug: mound of platelets at damage site, platelets attach to vWF and collagen fibers to form plug

18.Know that the long negative feedback loop within an HPX axis (between the X gland and the hypothalamus) is the most important regulatory negative feedback.

Most important regulatory feedback: The long negative feedback loop within an HPX axis (between X gland and Hypothalamus)

3.Consider potassium, calcium, sodium, and proteins. Is each of these ions more abundant in the intracellular or extracellular environment?

Na+ is more abundant out of the cell (extracellular) Ca2+ is more abundant out of the cell (extracellular) K+ is more abundant in the cell (intracellular) Proteins are more abundant in the cell (intracellular)

6.What components do we find most abundantly inside and outside of a cell? (Know this for potassium, sodium, calcium, proteins, and carbon dioxide).

Na+ is more abundant out of the cell (extracellular) Ca2+ is more abundant out of the cell (extracellular) K+ is more abundant in the cell (intracellular) Proteins are more abundant in the cell (intracellular) CO2 ??

9.With respect to negative feedback mechanisms, the greater the deviation (i.e., error signal), the (larger? smaller?) the correction.

Negative feedback: The greater the deviation, the larger the correction

1.Review the connections, similarities, and differences between the nervous and endocrine system.

Nervous system: neurons and neurotransmitters, electrical impulses, synapses on local target cells with local effects, quick, stops quickly after stimulus stops Endocrine system: glands/hormones, exposure throughout body, sometimes general sometimes specific effects, slow (seconds to days), effects long after stimulus stops

10.Norepinephrine is primarily used by the body as a neurotransmitter or a hormone? What about epinephrine?

Neurotransmitters: epinephrine and norepinephrine, from adrenal medulla, stimulate gland to release hormone

6.What are non-specific defenses?

Non specific defenses: skin and mucus membranes, inflammation (redness, swelling, heat, pain), fever, antimicrobial substances, phagocytes Non specific white blood cells: basophils, eosinophils, neutrophils, monocytes, Specific white blood cells: T and B lymphocytes

3.Do all cells respond to a hormone? What determines if a cell responds at all? Do all cells respond to the same hormone in the same manner? What determines how a cell will respond?

Not all cells respond to a hormone Receptors: determine cell response -a protein made by the target cell (protein synthesis, gene expression) Active site "fits" the hormone, Acts to convert or "transduce" the signal into a response

47.Which cell releases OPG? When is OPG released? Which cell releases OPGL? When is OPGL released?Describe the role of these molecules in calciumregulation.

OPG- osteoprotegerin, released by estrogen (gonads), secreted osteoblasts OPG- serves as a "decoy" receptor, it will bind to OPGL and prevents it from interacting with its receptor on preosteoclasts, thus inhibiting their differentiation into mature osteoclasts that resorb bone OPGL- osteoprotegerin ligand, AKA Rank ligand (RANKL) , released by PTH OPGL- binds to immature osteoclasts to create osteoclast to degrade bone matrix and put calcium back in plasma

45.How does parathyroid hormone target osteoblasts in order to increase bone resorption? What regulates the release of PTH?What gland releases PTH?

Osteoblasts - build bone; target cells for PTH PTH causes osteoblasts to release OPGL (osteoprotegerin ligand), also called RANK ligand (or RANKL) PTH: Low calcium levels on plasma trigger PTH release (humoral control) Parathyroid gland: releases PTH

14.What is oxygen carrying capacity? What determines oxygen carrying capacity? How do we calculate it?

Oxygen carrying capacity: g% hemoglobin/ 100mL blood x 1.34mLO2/ g% Hb Male: 21mLO2/100mL blood Female: 19mLO2/100mL blood

22.Know the different roles of PGE2, TXA2, and PGI2. Understand why COX-2 inhibitors result in increased tendency of clot formation and why COX-1 inhibitors result in increased risk of ulcers.

PGE2: prostaglandin E2 helps protect gastric mucosa TXA2: thromboxane A2 promotes clots PGI2: prostacyclin helps protect gastric mucosa, pro inflammatory, inhibits clots COX 1: less protection of gastric mucosa, leads to ulcers COX 2: increased risk of thrombotic cardiovascular events, PGI2 is blocked, but TXA2 still promoting clots

46.Know all functions of parathyroid hormone. Consider what would happen to our body if there was an increase in the amount of PTHcaused by a tumor. What about a decrease in PTH?

Parathyroid hormone: to regulate calcium in the blood Increased PTH: Increased calcium in the plasma Decreased PTH: Decreased calcium in the plasma Symptoms: osteoperosis(increased),bonestoothick(decreased)

6.Which class of hormones is the most abundant?

Peptides *all hormones that are not classified as steroids or amines can be assumed as peptide hormones

4.Know the components of plasma and the percentage of water in plasma

Plasma: Plasma fluid(the water inside blood vessels, but not in blood cells; 4-5%) Plasma water is moved across walls of capillaries by hydrostatic pressure Plasma is extracellular

24.What is a normal range of platelet counts? What is thrombocytopenia? What is the disorder "idiopathic thrombocytopenia purpura?" What physical signs develop in this condition? Know what causes petechiae and purpura.

Platelet counts: 150,000-300,000/ul Thrombocytopenia: reduced platelet counts Idiopathic Thrombocytopenia Purpura: tendency to bleed from many small venules and capillaries Physical signs: small purple blood leaks below skin called petechiae and purpura Treatment: whole blood transfusions, splenectomy

1.What are platelets derived from? How many are there per ul/ whole blood? Where are they made? Do they have nuclei?Know what platelets are, where they came from, their normal count/μL, how long it takes before they are no longer viable. Know the granule contents of a platelet.

Platelets: thrombocytes, derived from megakaryocytes, produced in bone marrow, life span 8-12 days, production stimulated by thrombopoietin from liver/kidney 150-200,000 platelets/ ul of whole blood Do not contain nucleus Granule contents: Mitochondria: make ADP and ATP ER and Golgi: make clotting enzyme and store calcium Prostaglandin: thromboxane A2 Actin, Myosin: important contractile proteins Factor XIII: fibrin stabilizing factor Growth Factor: good for repair of damaged cell walls

16.What is the meaning of the terms poikilocytosis and anisocytosis?

Poikilocytosis: cells of abnormal shape Anisocytosis: cells of abnormal size, indication of MCV

19.Know if EPO and hematocrit values should be higher or lower than normal under polycythemia vera, under secondary polycythemia, under conditions of renal failure, and under aplastic anemia. What about an athlete?

Polycythemia vera: EPO decreased or low normal, HCT is increased Secondary Polycythemia: EPO normal or increased, HCT increased Renal Failure: EPO: decreased EPO, increased HCT Aplastic anemia: EPO increased, HCT decreased Athlete: EPO increased because needs more oxygen, HCT is decreased

9.Notice the way enzymes are named. What can you say about enzymes whose names begin in "pro-" or end in "-ogen?" What is the enzymatic role of thrombin?

Pro- and -ogen: inactive enzymes Thrombin: acts on fibrinogen to form fibrin polymers

27.Propylthiouracil (PTU): Understand why it is given to patients, how it works, and its possible effects on HPT hormone levels and thyroid gland size/goiter.

Propylthiouracil: exogenous drug, blocks the peroxidase and organification process. PTU is used to treat hyperthyroidism and may cause a goiter

19.Know the different prostaglandins that can be converted from arachidonic acid and the key enzyme responsible for that conversion

Prostaglandins: cause the hypothalamus to elevate temperature set point, PGE2 is the main prostaglandin that does this Arachidonic acid: phospholipid in cell membrane

19.How is heparin removed after surgery for a patient on a heart-lung bypass machine.

Protamine: binds to heparin and removes it from circulation, causes shorter clotting times, used after surgery

3.Understand the process of protein packaging/processing. What is it?How does it work? Where, in the cell, does it happen?

Proteins: chains of amino acids linked by peptide bonds Denaturing of proteins: loss of structure leads to loss of function Folding and coiling is stabilized by bonds formed between the "R groups" of amino acids Shape (conformation) determines function Changing a single amino acid can change the shape of a protein Gene: a code which determines the sequence of amino acids in a protein

18.What is a pyrogen? Where can they come from? From lecture, what pyrogen does your own immune system release? How can these signals reach the hypothalamus when there is a blood-brain barrier?

Pyrogen: cause set point of hypothalamic thermostat to rise come from: macrophages and T lymphocytes Cytokines: breach the blood brain barrier to get to the hypothalamus

20.What is the lifespan of an RBC? What is the role of ATP in keeping a RBC viable, i.e., do they have aerobic respiration?

RBC lifespan: approx 120 days Role of ATP: stores for replacement of worn parts of the RBC Aerobic Respiration: ???

21.How and when are RBC's removed from circulation? What is the role of the macrophage and liver and spleen in the destruction of the RBC and the handling of breakdown products of hemoglobin (Hb)? What happens to Fe, heme, and globin? Know which components of a red blood cell are recycled, which ones are destroyed, and where are the components of a destroyed red blood cell are processed.Know the steps involved in the processing of pyrrole chains and excretion of bilirubin resulting from red blood cell destruction.

RBCs removed from bloodstream by reticular fibers and macrophages in liver and spleen, contents are destroyed (pyrrole chains) or recycled (globin chains, iron) Iron: becomes transferrin, then ferritin and stored in the liver Heme: (pyrrole) taken by albumin to hepatocyte to become conjugated, and then excreted Globin: becomes amino acid and can be redistributed Which components of RBC are recycled: globin and iron ^Destroyed: pyrrole chains ^where is it processed: hepatocyte 1. Red blood cell breaks down in macrophage 2.Macrophage consists of globin, pyrrole chains, and iron 3. Globin breaks down to amino acids and can be redistributed 4. Iron breaks down to transferrin and then to ferritin to be stored in liver 5. Pyrrole chains cannot be broken down yet 6. Albumin carries pyrrole chains to hepatocyte 7. Pyrrole chains start as unconjugated bilirubin and become conjugated bilirubin 8. Then conjugated bilirubin can be excreted in the bile or feces

1.Know how abundant RBCs are in the body(out of all cells in the body)and per microliter of blood.

RBCs: erythrocytes Hematocrit: % Volume of blood that is red blood cells ¼ of body cells (25 trillion; 4.5 - 5.5 x 10 6 cells / mm3)

16.How do we lose heat? What is the main way we lose heat? What if it is a very hot day with low humidity? What if it is a very hot day and high humidity (do we lose heat?) What if we are submersed icy waters? What if we are submersed in a very hot, hot tub? Consider a person who is starting to work on a coal mine (hot, humid environment)vs. another who has already been acclimatized to such conditions. How would they differ in their abilities to thermoregulate?Why?

Radiation: 60% of heat lost Very hot day and low humidity: we lose heat by sweating (evaporation) Very hot day and high humidity: we lose heat by convection (skin and muscle blood flow) much harder to lose heat! Submersed by icy waters: shivering to increase heat Very hot hot tub: Sweating (evaporation) drinking water, air flow (convection) Thermoregulate: person who has been acclimatized will regulate much easier in these conditions than the person who is new to these conditions

10.Know all the mechanisms of heat loss and their respective importance under different conditions and their limitations(e.g. evaporative cooling through sweating is reduced in high humidity environments, etc).

Radiation: 60% of heat lost, solar, sky thermal Conduction: to air and solid objects Convection: wind and water, skin blood flow Evaporation: sweat, respiratory

17.How is the rate of erythropoiesis regulated? Provide the complete feedback loop that controls this variable (RBC count.) What is sensed by the kidney in order to regulate the RBC count?

Rate of erythropoiesis: regulated by erythropoieten, a hormone that promotes release of reticulocytes Feedback loop: ??? Kidney: senses hypoxemia (low oxygen), and secretes erythropoieten

4.What are hormone receptors? In which general locations can they be found?

Receptors: protein made by target cell Three locations where it can be found: -inserted into plasma membrane, in cytoplasm, in the nucleus

8.What is the recipe for normal erythropoiesis? What are coenzymes? Which two are important for erythropoiesis? Discuss the role of folic acid and Vitamin B12 in erythropoiesis. Where does the body store these coenzymes? How does a lack of each affect the production and final appearance of the RBC? How and where is Vit B12 absorbed from the GI tract? What is a necessary requirement for normal B12 absorption? Where is this "factor" produced and released?

Recipe for Normal Erythropoiesis: Healthy stem cells Growth inducers (interleukins) Differentiation inducers Cell division (mitosis)- DNA replication, vitamin B12 and folic acid (coenzymes stored in the liver) Building blocks of DNA- Adenine, Thymine, Cytosine, Guanine Hemoglobin synthesis-amino acids, heme and iron Folic acid(vit B9): Leafy green vegetables (aspargus, spinach, etc), Greater demand during pregnancy for neural tube closure (week 4), Stored supply (liver; 6-9 months), Poor nutrition, alcoholism, sprue (celiac disease), and anti-cancer drugs interfere with absorption Vit B12: Meat, dairy, eggs, Stomach mucosa; parietal cells produce intrinsic factor, a glycoprotein which is necessary for Vitamin B12 absorption. Join in stomach, then Vit B12 is released and absorbed in the ileum., Anemia seen associated with poor nutrition, strictly vegan diet, gastritis or gastrectomy, gastric atrophy, when lack IF, Stored supply (liver; 3-5 years)

8.What are the components of the thermoregulation reflex arc? Where, anatomically, do you find them? Specifically, what are the effectors for thermoregulation? What are sensors? Where is integration?

Reflex arc: negative feedback mechanism Components: Thermoreceptors (sensory): Peripheral (in skin) detect cold and cool temperatures, prevent hypothermia, Central (preoptic area and anterior hypothalamus) heat and cold sensitive neurons Afferent Nerve Fibers Integration in anterior hypothalamus: activates cooling mechanisms Efferent nerve fibers to effectors: skeletal muscle and sweat glands Effectors of thermoregulation: cutaneous circulation, sweat glands, and skeletal muscle

32.Are people with malaria at an advantage in life? Do people with sickle cell disease have an advantage against malaria? What if someone has sickle cell trait AND malaria, does having the trait give them an advantage fighting malaria?

SS Trait: advantage against malaria, erythrocyte destruction means fewer parasites, easier for individuals to fight infection SS Disease: no advantage against malaria

13.What types of second messenger systems are used?

Second messengers; cAMP, DAG+IP3 used for Amine and Peptide Hormones

5.Understand the key propertiesof feedback mechanisms used to maintain homeostasis (redundancy, hierarchy, complexity). Be able to cite examples of eachproperty.

Sensor: detects deviation from set point Pre programmed correction: in triggered Output signal: activates an effector mechanism Redundancy: from molecular (genetic) to organ system level Complex: do not work in isolation, multiple synergistic or antagonistic mechanisms (ex: cortisol inhibits insulin) Hierarchy: ???

3.Understand the terms "sensor", "variable", "set point", "deviation", "compensation",and "integrator"in the context of maintaining homeostasis.

Sensor: detects deviation from set point Variable: anything that changes and can be measured (pH, temp) Set point: an optimal value for a variable Deviation: a change from set point Compensation: a return to set point, the amount of deviation determines the amount of compensation needed Integrator: brain and spinal chord

16.What is serum vs. plasma?

Serum: liquid that remains after blood has clotted Plasma: liquid that remains when clotting is prevented

36.Understand the different factors that can result in reduced growth (short stature).

Short stature: 1.Decreased GH 2.Defective receptor (Growth Hormone binding protein, GHBP) for GH on liver, Laron dwarfs- lack GHBP (GH binding protein)-300 worldwide-33% in Ecuador 3. Liver does not make IGF-1, African pygmy- normal GH, but lack IGF-1, IGF-I- adult (aka- somatomedin C)•IGF-II- fetal, Targets bone and cartilage

30.Explain how a single point mutation on a gene can affect the structure of a globin chain (sickle cell anemia or thalassemia major.) What is the exact change in the globin chain in these disorders? Under what oxygen conditions does this affect RBC shape in sickle cell disease. How does it change the cell's shape? Are there other globin chains made to compensate (e.g., HbF or HbE?)

Sickle cell anemia: mutation for B globin chain leads to HbS, valine (nonpolar) is used in place of glutamic acid (polar) in position 6, RBCs sickle under low O2 conditions, HbS: alpha and sickle beta chains Thalassemia major: all 4 alleles are mutated

37.What is somatostatin (GHIH)?

Somatostatin (GHIH): stops release of growth hormone

35.Considering the HPT, HPA, and HPL axes, which hormones inhibit growth and which hormones stimulate growth?

Somatotropin- growth hormone Somatostatin- stops release of growth hormone

5.Describe the three classes of hormones (amino acid derived, peptide/protein vs. lipid), their properties, and the examples of amine-based hormones and of steroid hormones discussed in class. Know that all remaining hormones can then be assumed to be peptide hormones.

Steroids: lipid-derived, hydrophobic- Ex: Cortisol, Aldosterone, Testosterone, Estrogen, Progesterone Peptides: Proteins (> 100 a.a.) or peptides (3-100 a.a.) (or modified, as glycoproteins); MOST hormones Amines (small, derived from an a.a., e.g. tyrosine, tryptophan) Ex: Dopamine (prolactin-inhibiting factor, PIF) - from hypothalamus, Thyroid Hormone (TH, T3 + T4 )- from thyroid, Norepinephrine / Epinephrine - from adrenal medulla

15.What mechanisms exist to trigger a hormone to be released? Know all three hormone release mechanisms and the examples of each discussed in class.Know what triggers the release of each of the hormones under humoral release mechanism discussed in class.

Substance in blood triggers hormone release Examples: Glucose levels regulate insulin and glucagon release Calcium levels regulate parathyroid hormone release Neural: Neuron releases neurotransmitter, which stimulates gland to release hormone. Examples: Oxytocin, ADH (from posterior pituitary, aka neurohypophysis); Epinephrine, Norepinephrine (from adrenal medulla) Humoral: Substance in blood triggers hormone release Examples: Glucose levels regulate insulin and glucagon release. Calcium levels regulate parathyroid hormone release Hormonal: Hierarchy of hormones through glands Examples: H-P-X axes (Hypothalamus, Pituitary, 3rd gland)H-P-T (H-P-Thyroid)H-P-A (H-P-Adrenal)H-P-G (H-P-Gonads)

19.UnderstandTH (T3+ T4) synthesis in the thyroid gland.Which one, triiodothyronine or tetraiodothyronine(thyroxine) is the most potent form of thyroid hormone and is responsible for most of the physiological effects of thyroid hormone? Which one is released in larger quantities by the thyroid gland?

T3- triiodothyronine, four times as potent as T4, the active form, released in larger quantities, 7% T4- thyroxine/ tetraiodothyronine, 93% most potent, responsible for most of the physiological effects of thyroid hormone

31.Thalassemia: what kinds are there and which globin chain is mutated and what types of globin chains are left to associate with each other?

Thalassemias: a thalassemia: Hemoglobin H, with 4 beta chains, is formed when there are not enough alpha chains, forms heinz bodies b thalassemia: prevent/ reduce beta chain production, accumulation of alpha chains

2.Does every system in the body help maintain homeostasis? Does every system have the same stringency with set points andallowed deviations? What is the specific role of the neural and endocrine systems in homeostasis? In what ways are these two systems different from each other? How are they similar?

The nervous and endocrine system are responsible for regulating body functions. Every system ?? Nervous system: neurons and neurotransmitters, electrical impulses, synapses on local target cells with local effects, quick, stops quickly after stimulus stops Endocrine system: glands/hormones, exposure throughout body, sometimes general sometimes specific effects, slow (seconds to days), effects long after stimulus stops

12.How do hormones that do not enter the cell convey chemical changes inside the cell?In general terms, how do second-messenger systems work and why are they so effective?

The second messenger system consists of hydrophilic proteins The hormones that are hydrophobic (need second messenger) attach to the hydrophilic transport proteins to enter the bloodstream Can go all the way across cell and nuclear membranes to bind receptor, act directly on gene transcription

40.If the African Pygmies and Laron dwarfs have enough GH, why are they still showing short stature?

They are still showing short stature because they're IGF-1 is either too low, or not there so the growth hormone cannot properly bind to target cells, growth is inhibited

4.Which of the following are pro-platelet activation/ pro-coagulants and which are anti-platelet/ anti-coagulants?Which are endogenous and/or exogenous? TXA2 (thromboxane A2), PGI2 (prostacyclin), heparin, coumadin/coumarin/warfarin, oxalate, citrate, EDTA, aspirin, anti-thrombin III, and protamine.

Thromboxane A2: activate platelets, procoagulants, endogenous PGI2: anticoagulant, endogenous Heparin: anticoagulant, exogenous Coumadin/coumarin/warfarin: anticoagulant, exogenous Oxalate: anticoagulant, endogenous Citrate: anticoagulant, endogenous EDTA, EGTA: anticoagulant, exogenous Anti-thrombin II: anticoagulant, endogenous Protamine: anticoagulant, exogenous

27.What is a thrombus? An embolus? How can they be treated clinically? That is, what needs to be injected? What can we give a patient to prevent clots while in the hospital? What test will be used to monitor clotting times while on this drug in the hospital? What can we give them when they are discharged to prevent clots? What test will be used to monitor their blood clotting times while on this medication and why should they limit their green-leafy vegetables?

Thrombus: formed when platelets begin to stick to wall of intact blood vessel Embolus: air bubble in blood Anticoagulant needs to be injected, heparin aPPT: used to check heparin in hospital PT test: monitors prothrombin, clotting times

20.How are levels of thyroid hormone and growth hormone dependent? What can extreme levels of cortisol do to non-essential functions of the body like reproduction or growth?

Thyroid hormone- dependent on 2nd messenger system, hydrophobic, bind to nuclear receptor to have direct effects on DNA transcription Growth hormone- dependent on somatostatin to stop its release Extreme levels of cortisol- cushing's syndrome/ disease

8.When we say hyperosmotic and hypertonic, are these words interchangeable? What is the difference between the two?Know the difference between a permeant and an impermeant solute. Know that urea is a permeant solute.

Tonicity: (isotonic, hypotonic, hypertonic solutions) refers to whether a solution will cause changes in cell volume Osmolality: (isosmotic, hyperosmotic, hypo-osmotic solutions) refers to the number of particles, regardless of permeability A solute can be classified as: Impermeant: effective Permeant: ineffective (ex: urea) Tonicity and osmolality are often interchangeable.

7.What are totipotent, pluripotent, multipotent, and unipotent stem cells? Be ready to match their descriptions and give examples of these types of stem cells.

Totipotent: new organisms plus extraembryonic membranes Pluripotent: new organism Multipotent: hemocytoblast, many lineages Unipotent: proerythroblast

2.Where does translation occur? Where, in the cell, does it happen?What material does it begin with and what material is created when finished?

Translation: occurs in the cytoplasm, the ribosome makes a protein using the code in the mRNA molecule Material begin with: RNA Material created: Protein

4.Identify the two mechanisms used to achieve homeostasis and differentiate between them and give examples. Which one is used the most by body systems to maintain homeostasis?Which of the two mechanisms can cause instability and vicious cycles? Under which conditions can positive feedback contribute to homeostatic balance(know the examples cited in lecture)?

Two mechanisms: Negative feedback: promotes stability, used most, returning to set point Positive feedback: promotes instability, leaving set point, leads to instability, vicious cycle, avalanche effect, can promote homeostatic balance during pregnancy and childbirth, blood clotting, generation of nerve signals, immune system

5.What happens in the vascular phase? What prostaglandin is released that helps with vasoconstriction?

Vascular Phase: myogenic contraction of smooth muscle Thromboxane A2: helps in vasoconstriction

20.What would happen with vitamin K deficiency? Who could present with such a deficiency?

Vit K deficiency: no blood clots, bleeding Patients: newborns, people with bile obstructions

48.What is the role of vitamin D in calcium regulation?

Vitamin D: required for calcium absorption from intestinal tract and for bone deposition and absorption Vitamin D3: cholecalciferol Active Vitamin D: calcitriol

11.Understand why vitamin K is important for hemostasis. Know the clotting factors that need vitamin K to be activated. How do we obtain vitaminK? Why does it require bile to be absorbed by our intestines?

Vitamin K: clots blood Clotting factors II, VII, IX, X need Vitamin K Vitamin K: found in green veggies, grains, red meats Fat soluble vitamin, need bile salts to absorb it

12.Know the role of the following molecules in hemostasis: vitamin K, antithrombinIII, tissue plasminogen activator (tPA)

Vitamin K: needed as coenzyme in hepatocyte to activate factors II, VII, IX, X and protein C Antithrombin III: plasma protein that bind to heparin tPA: activates plasminogen involved in clot dissolution

1.How much of our body is water? Know the percentage of total body weight accounted for water and by each body fluid compartment.

Water: 60% (45-75%) of our body weight Weight in water by kg: (your weight Lb/2.2) x 0.6 Intracellular water (ca. 40% of body weight) Extracellular water (ca. 20% of body weight)

6.Are we ever at (or locked at) our set point? When correction is made does it end AT the set point?

We are NOT locked at set point. Correction: returns to set point (negative feedback

12.Is whole blood an extracellular fluid? IF not, what part of whole blood would be extracellular fluid?

Whole blood: Plasma: extracellular fluid WBCs and RBCs: intracellular fluid

Define the components of whole blood. What components do you find in the formed element portion of whole blood? What components do you find in the plasma? What are normal blood values of protein? Glucose? Electrolytes?

Whole blood: Plasma (55%), Formed Elements (45%) Formed Elements: RBCs (99.9%), Platelets & WBCs (0.1%) Plasma: Water (92%), Plasma Proteins (7%), Other Solute (1%) Plasma Proteins: Albumins (60%), Globulins (35%), Fibrinogen (4%), Regulatory Proteins (<1%) Glucose: <1%,othernutrients Electrolytes: 1%, ions used for for vital cellular activity

28.What are the tests used to determine if someone's intrinsic or extrinsic pathways are compromised? Understand the uses of the aPTT and of the PT test.

aPTT test: activated partial thromboplastin time test, detects deficiency of factor VIII, used for heparin treated patients, prolonged time = deficiency PT test: prothrombin time test, detects deficiency of factor VII, used in coumarin treated patients, prolonged time = deficiency

9.What are catecholamines?

epinephrine, norepinephrine, and dopamine

29.Know the causes, consequences, and special considerations, of all types of anemia discussed in lecture.

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