N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
Stress & disease
● Trigger: Perceived or anticipated threat – stress is not all created equal, what stresses one
person may not stress another
● 3 Major Systems: SNS/HPA/Immune (see power point slides 12 & 13)
o SNS: Sympathetic nervous system, (RAPID) Catecholamines: Epinephrine &
Norepinephrine, fight or flight
o Rapidly released by 2 sources – directly from stress trigger, adrenal medulla
(chromaffin cells in response to CRH)
o Regulates cardiovascular, pulmonary, hepatic, skeletal muscle, and immune
system
o Stimulates two classes of receptors (alpha adrenergic receptors, beta adrenergic
receptors)
▪
Overall Goal: Fight or Flight (Blood and O2 delivery) (Alertness)
● Mobilize energy (increase blood glucose)
o HPA axis: Hypothalamus-Pituitary-Adrenal
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
▪
Adrenal cortex (Cortisol is key player), adrenals secrete cortisol, anything
that blocks this pathway affects the body’s ability to participate in fight or
flight response (Addison's disease)
▪
Hypothalamus secretes corticotropin-releasing hormone (CRH)
▪
Pituitary releases adrenocorticotropic hormone (ACTH)
● Goal: Mobilize energy (increase blood glucose)
▪
Adrenal medulla Epinephrine and Norepinephrine
● Goal: See above (SNS)
● Epinephrine released causes increased force of cardiac
contraction, increased lipolysis, increased blood glucose levels
o Immune: Innate (Inflammation) and Adaptive (Humoral & Cellular)
▪
Acute: Beneficial
● Inflammation: Inhibits initial response affecting Blood pressure
(See SNS effects on Blood pressure)
▪
Chronic: Harmful
● Cortisol (prolonged effect):
o Pro-inflammatory
o Suppresses humoral and cellular immunity
o Chronic effects of elevated cortisol: Cushing syndrome,
obesity, sleep deprivation, lipid abnormalities, HTN, DM,
loss of bone density, atherosclerosis, ulcers, emotional
disorders
o CVD, cancer, obesity, HTN, DM, also
autoimmune/inflammatory diseases
● Catecholamines (prolonged effect):
o Pro-inflammatory effects & counteracts PNS
o Catecholamines: Chronic stress induced release of
norepinephrine may cause plaque formation in blood
vessels, MI, stroke, autoimmune d/o
● Understand and apply: GAS, HPA axis; effects of cortisol and
neuroendocrine/immune responses to stress; Effects of stress on inflammatory
system.
o GAS – general adaptation syndrome, noxious stimuli (cold, injury, restraint)
caused structural changes in rats. Enlargement of adrenal gland. Thymic and
other lymphoid structure atrophy. Development of bleeding ulcers in the stomach
and duodenal lining.
▪ 1. Alarm stage, 2. Resistance/Adaptation stage, 3. Exhaustion stage
o Effects of cortisol (hydrocortisone) – released in response to adrenocorticotropic
hormone (ACTH). Regulates arousal, cognition, mood, sleep, metabolism,
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
cardiovascular tone, growth, & reproduction. Stimulates gluconeogenesis,
elevates the blood glucose level, affects protein metabolism, powerful antiinflammatory, and immunosuppressive agent, “stress hormone.”
o Effects of neuroendocrine/immune responses to stress – increase in blood
pressure, pupil dilation, goosebumps, increase sweat gland action, increase
arteriole smooth muscle contraction.
▪
Short term effects of stress and immune system: increased colds and
infections
▪
Long term effects of stress: cardiovascular disease, cancer, arthritis,
Multiple sclerosis, IBS, fibromyalgia, DM, obesity, HTN
o Effects of stress on inflammatory system – allostasis is stability through change,
allostatic overload causes overactivation of adaptive systems, may lead to
disease, highly individualized.
o Allostatic overload – allostatic is stability through change. Overload is chronic
overactivation of adaptive regulatory physiologic systems that may lead to
pathophysiology and onset of disease.
o HPA Axis pathway –
Fluids & Electrolytes/ Acid-Base Balance:
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
● Fluid: compartments and movement (plasma, interstitial, intracellular)
o Plasma – intravascular fluid (blood)
o Interstitial – the space between cells, outside the vessels
o Intracellular – inside cells, 2/3 of Total Body Water
o Extracellular ⅓ of TBW
● Starling forces (4 forces relating to Net Filtration)
o Starling forces – forces favoring filtration minus forces opposing filtration, forces
favoring reabsorption
1. Capillary hydrostatic pressure (BP – water pushing)
2. Interstitial oncotic pressure (water pulling)
3. Plasma oncotic pressure (water pulling)
4. Interstitial hydrostatic pressure (water – pushing)
● Edema (cause/process/result)
o Cause – increased intravascular hydrostatic pressure, lack of albumin, loss of
plasma proteins to interstitial space
o Process – decreased capillary oncotic pressure, increased tissue oncotic pressure
o Result – blood clot, swelling, fluid buildup
● Pulmonary edema – excess fluid in lungs, caused by heart
● Pericardial Effusion – buildup of fluid surrounding heart, puts pressure on heart until it
can’t pump
● Cerebral edema – increased fluid/swelling and intracranial pressure, skull is unable to
expand to accommodate
● Sodium, chloride, and water balance (hormones affecting this):
1. ANP & BNP – natriuretic peptide system
▪ ANP/BNP – released when increase in sodium, increased plasma volume
> increased atrial stretching detected by atrial endocrine cells >ANH &
BNP released > increased sodium and water secretion > decreased blood
volume and BP
▪ BNP – lab you will see ordered usually for patients with CHF with too much
fluid
▪ Benefits of ANP & BNP = vasodilation (blood vessels are bigger, decreased
BP)
▪ Increased sodium and water excretion
2. ADH – Antidiuretic Hormone, release stimulated by posterior pituitary gland
when:
▪ Increased blood osmolality (concentrated)
▪ Decreased blood volume (drop in BP)
▪ Effects: limits water excretion (kidney), water retention = decreased plasma
osmolality, increased plasma volume
3. RAAS (Renin-angiotensin-aldosterone) – system activated by decreased BP >
decreased renal perfusion > renin > release of angiotensin II (vasoconstrictor),
aldosterone (sodium retention thus fluid retention)
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
4. Symptoms of Syndrome of Inappropriate ADH (SIADH) – hyponatremia, low urine
output, lethargy/confusion, vomiting/cramping
● Osmolality (tonicity): (Normal serum osmolality: 280-294 mOsm)
o Osmosis – movement of water through semipermeable membrane from areas of low
to high solute concentration
● Terminology: Isotonic, Hypertonic, Hypotonic
o Isotonic – same osmotic pressure outside RBC as pressure inside, normal RBC.
Isotonic fluids have the same concentration of particles as ICF.
o Hypertonic – RBC shrinks. Hypertonic fluids have a higher concentration of
particles than ICF. Higher osmotic pressure shifts fluids from the cell into the ECF.
Hypotonic – RBC swells, lower concentration of particles
▪ (How is fluid movement affected?)
▪ Water excess (hypervolemia) – hypotonic fluids used to treat cellular
dehydration, used to “dilute” plasma. Hypotonic fluids have a lower
osmotic pressure than isosmotic fluids, and water is pulled from the hypoosmotic fluid space into the isosmotic fluid space.
▪ Water deficit (hypovolemia) – hypertonic fluids used to temporarily treat,
used to expand vascular volume. Hypertonic fluids have a greater osmotic
pressure than isosmotic fluids and tend to pull water from the isosmotic
fluid space into the hyperosmotic fluid space
● Electrolytes
o Sodium (Primary extracellular cation) (Nml range: 135-145 mEq/L)
▪ Controls ECF osmolality & fluid balance; Na-K pump
● Primary determinant of serum osmolality
o
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
▪
o
Hypernatremia – high concentration of sodium in blood (cells shrink),
causes water to shift out of cells. Symptoms: signs of dehydration, excess
fluid in tissues. Manifestations: intracellular dehydration, convulsions, PE,
tachycardia
▪ Hyponatremia – low concentration of serum sodium (cells swell), related to
sodium loss / water excess or inadequate intake of sodium. Manifestations:
cerebral edema & increased intracranial pressure
Chloride (follows sodium—most of the time) (Nml range: 96-106 mEq/L)
o
Potassium (Primary intracellular cation) (Nml range: 3.5-5.0 mEq/L)
▪ Controls ICF osmolality & fluid balance
▪ resting membrane potential; CARDIAC, smooth, and skeletal muscle
contraction; pH;
Na-K pump
▪ Hyperkalemia – high potassium in blood (level >5.0)
▪ Hypokalemia – low potassium in blood (level <3.5)
● Acid-Base Balance
o pH (nml range 7.35-7.45) (“Perfect” pH=7.4)
o PaCO2 (nml range 35-45) (Acid/Respiratory)
o HCO3 (nml range 22-26) (Base/Renal-Metabolic)
o Plasma buffering systems - bicarbonate-carbonic acid
● Acidosis vs. Alkalosis
o Acidosis – more hydrogen, pH is low (acidic), excrete more H+ & generates more
HCO3
▪ CNS depression, hyperkalemia, arrythmia
o Alkalosis – less hydrogen, pH is high (alkaline), kidneys retain more H+ & excrete
more HCO3
▪ CNS excitability, hypokalemia, arrythmia
● Respiratory vs. Metabolic
o ABG – arterial blood gas components: pH, bicarbonate
o Respiratory and renal system work together to maintain pH balance
o Lungs regulate CO2 levels, excrete CO2 & H2O, CO2 = acid
▪ Increased RR = Increased CO2 exhaled = Decreased plasma CO2
▪ Decreased RR = Decreased CO2 exhaled = Increased plasma CO2
(acidosis)
o Renal responds more slowly than respiratory
o Respiratory: imbalance leads to altered lung function
▪ Acidosis (<7.35): hypoventilation, pneumonia, pulmo edema
▪ Alkalosis (>7.45): hyperventilation (releasing more CO2), pulmo disease
(ABG = elevated pH with low CO2)
o Metabolic: imbalance leads to acid-base disorders
▪ Acidosis (<7.35): DKA, renal failure, starvation, “shock”
▪ Alkalosis (>7.45): vomiting (i.e. taking too many antacids)
● ABG = elevated pH & elevated HCO3
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
● GI system:
o Stomach is Acid
o Gut is Base
Normal range for following lab values:
Na+ 135-145
Cl- 96-106
K+ 3.5-5.0
pH 7.35-7.45
PaCO2 35-45
HCO3 22-26
Clinical manifestations of hypokalemia: low potassium
Cardiac dysrhythmia, glucose intolerance, impaired urinary concentrations, renal tissue
damage, interstitial fibrosis, tubular atrophy
Clinical manifestations of hyperkalemia: too much potassium
Restlessness, cramping, diarrhea, muscle weakness, loss of muscle tone, paralysis,
bradyarrhythmia
Hematology:
● Understand alterations in hematopoiesis and erythropoiesis (cause/results)
o Hematopoiesis: blood cell production, formed from stem cells in bone marrow.
Bone marrow is also called myeloid tissue. Regulation by growth factors (controls
for correct proportions of each cell type). Stem cells can be anything they want to
be, “have a choice.”
▪
▪
Hematopoiesis occurs through life, increases in response to a need to
replenish aged/destroyed cells or in response to infection.
Long term stimuli such as chronic diseases cause a greater increase in
hematopoiesis than do acute conditions such as hemorrhage.
o Erythropoiesis: erythropoietin is a hormone which regulates red blood cell
production. In bone marrow there is an increase in hemoglobin, red blood cell
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
production. Erythropoietin is made in kidney. Reticulocytes will show RBC
development, increase reticulocytes. Main stimulus is a lack of oxygen.
▪
In healthy humans, total volume of circulating erythrocytes remain
constant. However decreased oxygen of blood affects RBC. Body responds
in 2 ways: 1) by increasing the intake of oxygen through increased
respiration, 2) by increasing the oxygen-carrying capacity of the blood
through increased erythropoiesis.
● Extrinsic factors – external / B cells attack invaders outside the cells
● Intrinsic factors – internal / T cells attack invaders inside the cells
● Be familiar with the following lab values for complete blood count (CBC) and their
clinical significance (Ex: increased WBC—infection/inflammation)
CBC complete blood count:
o HGB: 14-18 (male), 12-16 (female)
▪
High levels = low O2 in blood
▪ Low levels = body not getting enough oxygen
o HCT: 42-52% (male), 37-47% (female)
▪
High levels = too many rbc, can mean dehydration
▪ Low levels = blood has too few healthy rbc
o WBC: normal range: 5,000 - 10,000 men and nonpregnant woman
▪
o
o
o
o
o
o
o
o
o
greater than 10,000 is sign of infection/inflammation
▪ low levels = low immunity
RBC: 4.5-5.5 (women and men), range is lower for children and newborn
Neutrophils: 50-62%, phagocytosis in early inflammation
Band neutrophils: 3-6%
Lymphocytes: 25-40%, humoral and cell-mediated immunity
Monocytes: 3-7%
Eosinophils: 0-3%
Basophils: 0-1%
Erythrocyte: gas transport in circulating blood
Macrophage: mature monocyte
● Classification and pathophysiology of the anemias (iron deficiency, pernicious,
folate deficiency; normocytic-normochromic)
o Anemia: Reduction in the total number of erythrocytes in the circulating blood or
in the quality or quantity of hemoglobin. Impaired erythrocyte production. Acute
or chronic blood loss, Increased erythrocyte destruction, Combination of the
above
o Iron deficiency: most common form of anemia
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▪
Increased demand for iron and/or hematopoiesis
▪
Increased iron loss
▪
Decreased iron intake or absorption
N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
▪
o
o
o
o
o
o
Exam findings are cheilosis (fissures at the corners of the mouth), angular
stomatitis, glossitis (smooth appearance of tongue/loss of papillae),
koilonychia (spooning of nails)
Pernicious: vitamin B12 deficiency (macrocytic normochromic anemia), absence
of intrinsic factor
Folate deficiency: lack of folate, folate helps make RBCs, typically no neuro
symptoms, both are coenzymes for nuclear maturation and DNA synthesis
(macrocytic normochromic anemia)
Sickle cell anemia – inherited abnormal hemoglobin S
Normocytic, macrocytic, microcytic – identified by size
Normochromic, hypochromic – identified by hemoglobin content
Polycythemia: overproduction of RBC
▪
Primary absolute vs. secondary absolute
▪
Primary Absolute: excessive proliferation of erythroid precursors in
marrow
▪
Secondary Absolute: increase in erythropoietin, as a normal response to
chronic hypoxia (ex: altitude, copd), or response to erythropoietinsecreting tumors
o Relative polycythemia: fluid loss (dehydration) results in relative increases of
RBC, HGB, and HCT values
● Pathophysiology of polycythemia vera
o Vera: (Primary) neoplastic, nonmalignant tumor, patients must stay hydrated,
Abnormality proliferation of stem cells in the bone marrow; thick blood; BV
occlusions, Intense, painful itching intensified by heat or water, Normal
erythropoietin production.
● Alterations in leukocyte function (include adult leukemias: ALL, AML, CLL, CML)
o Leukocytosis: increase in leukocytes, a normal protective physiologic response to
physiologic stressors like infection
o Leukopenia: decrease in leukocytes, not normal and not beneficial, low WBC
count predisposes a patient to infections
o Leukemia: malignant disorder of the blood and blood-forming organs, excessive
accumulation of leukemic cells, pancytopenia if cells crowd bone marrow
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▪
Acute Leukemia: presence of undifferentiated or immature cells, usually
blast cells; abrupt, rapid onset and course
▪
Chronic Leukemia: predominant cell is mature but does not function
normally; gradual onset; prolonged clinical course
▪
Myeloid: from bone marrow, granulocytic
▪
Lymphocytic: lymphoid, from B & T cells progenitors
▪
Acute: rapid onset, more immature cells
▪
Chronic: slower growth of more differentiated cells
N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
o
o
o
o
ALL (Acute Lymphocytic Leukemia): most common in children, high B cells
AML (Acute Myelogenous Leukemia): high Myeloblasts
CML (Chronic Myelogenous Leukemia): high neutrophils
CLL (Chronic Lymphocytic Leukemia): high T cells
● Impaired hemostasis and clotting (Virchow Triad)
o Virchow Triad:
▪
(1) injury to the blood vessel endothelium
▪
(2) abnormalities of blood flow
▪ (3) hypercoagulability of the blood
o Impaired hemostasis: the arrest of bleeding, depends on adequate numbers of
platelets, normal levels of coagulation factors, & absence of defects in vessel
walls. Diminished hemostasis results in either internal or external hemorrhage,
defined as copious or heavy discharge of blood from blood vessels.
▪
Defects of primary hemostasis – platelet defects or von Willebrand
disease, usually present with small bleeds in skin or mucosal membrane
▪
Defects of secondary hemostasis – coagulation factor defects, bleeds into
soft tissue, muscle, joints, intracranial bleeds may occur
● Pathophysiology (general) of child hematology disorders: Sickle cell anemia
o Sickle cell anemia: change in shape of red blood cell. A homozygous form is the
most severe. It results when the individual inherits two copies of Hb S. Hb S is
soluble and is fine when properly oxygenated. However, when oxygen decreased,
polymers realign causing the sickle shape. Decreased oxygenation, pH,
dehydration, acute illness, stress, temperature change, and high-altitude lead to
sickling.
o Sickle cell disease: a group of autosomal recessive disorders characterized by the
production of hemoglobin S (Hb S) within the erythrocytes.
● Exemplar conditions:
o Anemias: Reduction in the total number of erythrocytes in the circulating blood or
in the quality or quantity of hemoglobin.
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▪
Iron deficiency – most common cause of anemia, 500 million cases
worldwide, higher prevalence in less developed countries. Symptoms:
swollen lymph nodes, fever, night sweats, nose bleeds, severe infections,
bleeding easily, bone pain, red spots on skin, weight loss
▪
Microcytic – microcytic-hypochromic anemias are characterized by
abnormally small red cells with low amounts of hemoglobin, most
common anemia worldwide. Related to: disorders of iron metabolism,
disorders of porphyrin and heme synthesis, disorders of globin synthesis,
poor or incomplete nutrition.
▪
Macrocytic – macrocytic-normochromic anemias are large abnormally
shaped erythrocytes, normal hemoglobin concentrations. Defective DNA
N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
synthesis caused by vitamin b12 deficiency or folate deficiency (pernicious
anemia & folate deficiency)
▪
Normocytic-normochromic anemia – normal size, normal hemoglobin
concentration (aplastic anemia, posthemorrhagic anemia, hemolytic
anemia)
o GI Bleeding: use of medications such as aspirin or NSAIDS drugs can cause GI
bleeding. Surgical procedures that decrease stomach acidity and other functions
and eating disorders can cause bleeding.
o Polycythemia Vera: (PV) neoplastic, nonmalignant, abnormality proliferation of
stem cells in the bone marrow; thick blood; BV occlusions; intense, painful
itching intensified by heat or water; normal erythropoietin production
o HIT (Heparin-induced Thrombocytopenia): heparin is a common cause of druginduced thrombocytopenia, 4% of individuals treated with unfractionated heparin
develop this. HIT is immune-mediated, adverse drug reaction caused by IgG
antibodies against the heparin-platelet factor 4 complex leading to platelet
activation through platelet Fc receptors
o ITP (Immune Thrombocytopenia): platelets have short life span previously
referred to as idiopathic thrombocytopenic purpura, is the most common disorder
of platelet consumption. Autoantibodies bind to the plasma membranes of
platelets, causing platelet sequestration and destruction by mononuclear
phagocytes in the spleen and other lymphoid tissues at a rate that exceeds the
ability of the bone marrow to produce them. Clinical – petechial rash occurs after
a viral illness, petechiae can develop into asymmetric bruising, epistaxis,
hemorrhagic bullae of gums/lips, intracranial hemorrhage.
o Vitamin K deficiency – fat-soluble vitamin is required for synthesis and regulation
of prothrombin, the procoagulant factors and anticoagulant factors within the
liver. The most common cause is parenteral nutrition in combination with
antibiotics that destroy normal gut flora (rarely due to dietary intake).
o DIC (Disseminated Intravascular coagulation) – blood clusters into clumps and
can be dangerous. An acquired clinical syndrome characterized by widespread
activation of coagulation resulting in formation of fibrin clots in medium and
small vessels or microvasculature throughout the body. Widespread clotting may
lead to blockage of blood flow to organs, resulting in multiple organ failure.
o Hemolytic Disease of Newborn – blood disorder that occurs when the blood types
of a mother and baby are incompatible. Hereditary: caused by abnormalities of
RBC membrane or cytoplasmic contents; present at birth.
o Hemophilia – hemophilia(s) are a group of inherited bleeding disorders resulting
from mutations in coagulation factors.
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▪
Hemophilia A: X-linked recessive conditions, mutation in F8 gene,
clotting factor VIII (classic hemophilia), most common hereditary disease
associated with life-threatening bleeding.
▪
Hemophilia B: X-linked recessive conditions, clotting factor IX (Christmas
factor), mutation in F9 gene.
N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
▪
Hemophilia C: Autosomal recessive condition, clotting factor XI (plasma
thromboplastin antecedent)
Disease Focus: Hematology and clotting concepts; various types anemias and
lymphomas.
Endocrine:
● Structure and function of Endocrine system (Gland, hormone, target, effect)
o Function – stimulation and control of growth and development. CNS
development. Coordination and differentiation of the male & female reproductive
systems. Maintenance of internal environment. Homeostasis. Adaption to
emergency demands of body. Endocrine, nervous, and immune systems work
together to regulate responses to the internal/external environments.
o Glands – pituitary, adrenal, thyroid, parathyroid, pancreas release hormones.
o Hormone – released into the circulatory system by endocrine glands. Water
soluble hormones circulate in free, unbound forms, short-acting response, bind to
surface receptors. Lipid soluble hormones are primarily circulating bound to a
carrier. Rapid and long-lasting response. Bind to plasma membrane and can pass
through the membrane. Bind to intracellular receptors.
o Target – cells with appropriate receptors for specific hormone is a target cell.
Hormone receptors of target cell recognize and bind specifically with hormones.
They initiate a signal to appropriate intracellular effectors.
● Positive feedback loops:
o Occurs when a neural, chemical, or endocrine response increase the synthesis
and secretion of a hormone.
o Ex: HPA axis and thyroid gland – positive feedback occurs when thyrotropinreleasing hormone (TRH) is released from the hypothalamus in response to low
thyroid hormone levels.
● Negative feedback loops:
o Occurs when a changing chemical, neural or endocrine response to a stimulus
decreases the synthesis and secretion of a hormone.
o Ex: Negative feedback occurs when increasing levels of T4 and T3 feedback on
the pituitary and hypothalamus to inhibit TRH and TSH synthesis and decrease
the synthesis and production of thyroid hormones.
● Up-regulation and down-regulation
o Up-regulation: low concentrations of hormone increase the number or affinity of
receptors per cell *more receptors appear on cell* flowers growing analogy
o Down-regulation: high concentrations of hormone decrease the number or
affinity of receptors *receptors decrease on a cell*
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
● Key hormones and mechanism of:
o Anterior pituitary - secretes tropic hormones that affect the physiologic function
of specific target organs
▪
Melanocyte-stimulating hormone (MSH) – promotes melanin
▪
Follicle-stimulating hormone (FSH) – initiates follicular growth,
stimulates ovarian follicles to secrete estrogen
▪
Luteinizing hormone (LH) – stimulates secretion of estrogen and
progesterone, production/secretion of testosterone in testes
o Posterior pituitary – derived from the hypothalamus and is comprised of 3 parts.
The posterior pituitary secretes two polypeptide hormones: Antidiuretic hormone
(ADH) and Oxytocin
▪
ADH – major homeostatic function of posterior pituitary, regulates the
control of plasma osmolality
▪
Oxytocin – responsible for contraction of uterus and milk ejection in
lactating women, may affect sperm motility in men
o Thyroid hormones:
▪
TH: thyroid hormone, secreted in response to TSH, TH secreted as 90%
T4 and 10% t3.
▪
TSH: Thyroid Stimulating Hormone triggers release of thyroid hormone
▪
T3: active form, triiodothyronine, regulates protein synthesis & metabolic
effects
▪
T4: tetraiodothyronine (thyroxine), most T4 is concerted to T3, regulates
protein synthesis & metabolic effects
▪
Bound to thyroxine-binding globulin, thyroxine-binding prealbumin, or
albumin (as reserve and for transport)
▪
Affect growth and maturation of tissues, cells, metabolism, heat
production, and oxygen consumption.
o Parathyroid hormone: the single most important factor in the regulation of the
serum calcium concentration
o Pancreas – endocrine gland that produces hormones and exocrine gland that
produces digestive enzymes.
▪
alpha cells – secrete glucagon
▪
beta – secrete insulin and amylin
▪
delta cells – secrete gastrin and somatostatin
▪ F cells – secrete pancreatic polypeptide
o Adrenocortical hormones – ex: hydrocortisone, increase the effects of
catecholamines – norepinephrine and epinephrine
o Adrenomedullary hormones – adrenal glands are on the upper poles of kidneys
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
▪
Cortisol – stabilize blood glucose
▪
Epinephrine – increase HR
▪
Aldosterone – maintain BP, increases sodium retention
▪
Sex hormones (estrogen and androgens) – male/female function
● Ways target cells fail to respond to hormone (cell-surface receptors and
intracellular disorders; circulating inhibitors)
o Cell surface receptors – inappropriate response by target cell. Disorders can be
caused by
▪
Decrease in number of receptors
▪
Impaired receptor function
▪ Presence of antibodies against specific receptors
o Intracellular disorders can be caused by
▪
Inadequate synthesis of a second messenger
▪ Intracellular enzymes or proteins are altered
o Circulating inhibitors – caused by dysfunctional or ectopic hormones
▪
Inadequate biologically free hormone
▪
Hormone degraded at an altered rate
▪
Circulating inhibitors
▪
Ectopic production of hormones
● Compare and contrast hypo/hyper disorders:
o ADH: Antidiuretic hormone, produced in hypothalamus, released from posterior
pituitary. Stimulates vasoconstriction increasing blood flow. Increases water
reabsorption. Low blood osmotic pressure, high blood volume and alcohol inhibit
ADH secretion.
o DI – Diabetes insipidus characterized by abnormally low ADH secretion, (too
little), Serum Na+ is high, Serum osmolality is high, urine osmolality is high.
o SIADH – Syndrome of inappropriate antidiuretic hormone secretion (too much),
characterized by high levels of ADH. Serum Na+ low, Serum osmolality is low,
urine osmolality is high.
o Hypopituitarism – the absence of one or more anterior pituitary hormones or the
complete failure of all anterior pituitary hormone functions.
o Hyperpituitarism – caused by pituitary adenomas
▪
Primary adenoma – pituitary adenomas usually are benign/slow growing
tumors that arise from cells of anterior pituitary
▪ Expansion of pituitary adenoma causes neurologic and secretory effects
o Hypothyroidism – (too little) Hashimoto’s (primary)
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
▪
Clinical: loss of hair, coarse brittle hair, periorbital edema, puffy face,
normal/small thyroid, bradycardia, constipation, cold intolerance, muscle
weakness, edema of extremities.
o Hyperthyroidism – thyrotoxicosis, too much, (Grave’s disease). Hyperthyroidism
resulting from nodular thyroid disease. Goiter. Manifestations related to
hypermetabolic state.
▪
Clinical: thin hair, exophthalmos (eyes enlarged), enlarged thyroid,
tachycardia, weight loss, diarrhea, warm skin/sweaty palms, pretibial
edema.
▪
Thyrotoxic crisis (thyroid storm): includes fever, tachycardia, rapid HR,
hypertension, neurological/GI abnormalities. HTN may be followed by
congestive heart failure associated with hypotension and shock.
o Hypoparathyroidism – ex: damage to parathyroids during thyroid surgery
o Primary hyperparathyroidism – excess secretion of PTH from one or more
parathyroid glands
o Secondary hyperparathyroidism – increase in PTH secondary to chronic disease
▪
Manifestations: hypercalcemia, hypophosphatemia, hypercalciuria
(kidney stones), excessive urinary calcium excretion
o Hypocortisolism – low levels of cortisol secretion, develops either because of
inadequate stimulation of the adrenal glands by ACTH or because of a primary
inability of the adrenals to produce and secrete adrenocortical hormones.
(Adison’s)
o Hypercortisolism – hyperfunction that increases secretion of cortisol (Cushing
syndrome, Cushing disease)
o Addisons’ – primary adrenal insufficiency. Progressive hypo functioning of the
adrenal cortex. Inadequate production of cortisol aldosterone. Cause: 70%
idiopathic atrophy (autoimmune)
▪
Clinical: weight loss, fatigue, weakness, hypotension, tachycardia,
decreased body hair, hypoglycemia, electrolyte imbalance, fever, etc.
o Cushing’s – disorder of adrenal cortex
▪
Cushing’s Syndrome: group of clinical symptoms of excessive level of
cortisol, regardless of cause. Endogenous = rare, adrenal tumors.
Exogenous (latrogenic) = most common cause.
▪
Cushing disease: excessive anterior pituitary secretion of ACTH.
Excessive production of ACTH > signals adrenal glands to produce
cortisol. Most common cause of excess endogenous cortisol production by
adrenal glands. Endogenous cause (rare, 2nd most common cause of CS) is
internal. Exogenous is external like taking meds (hydrocortisone).
● Clinical: weight gain, truncal obesity, weakness/atrophy, moon
face, buffalo hump, hypertension, woman have facial hair,
hyperglycemia.
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
o Pheochromocytoma – hyperfunction of the adrenal medulla caused by
pheochromocytomas (chromaffin cell tumors) or sympathetic paragangliomas of
the adrenal medulla. Causes excessive production of norepinephrine.
o Hyperaldosteronism – characterized by excessive adrenal secretion of
aldosterone.
▪
Primary hyperaldosteronism (Conn Syndrome) – caused by excessive
secretion of aldosterone from an abnormality of the adrenal cortex,
usually a single benign aldosterone-producing adrenal adenoma.
▪
Secondary hyperaldosteronism – results from an extra-adrenal stimulus of
aldosterone secretion, most often through the secretion of excess
angiotensin II in response to decreased circulating blood volume and
decreased delivery of blood to the kidneys.
● Exemplar conditions:
o SIADH – Syndrome of inappropriate antidiuretic hormone secretion (too much),
characterized by high levels of ADH. High ADH cause retention of excess free
water, leading to hyponatremia and hypoosmolality.
o DI – diabetes insipidus is characterized by abnormally low ADH secretion. Low
ADH results in excess free water loss leading to hypernatremia and
hyperosmolality.
o Hypothyroidism – underactive, loss of hair, coarse brittle
hair, periorbital edema, puffy face, normal/small thyroid,
bradycardia, constipation, cold intolerance, muscle weakness,
edema of extremities. Deficient in production of TH by thyroid
gland. (Hashimoto’s (autoimmune condition, not thyroid
disease) is the most common cause of primary hypothyroidism
in the US)
▪ Primary hypothyroidism (Hashimoto’s) – increased levels
of TSH and caused by autoimmune thyroiditis, loss of thyroid
tissue, medication, and iodine deficiency. Thyroid is the
problem
▪ Secondary hypothyroidism – decreased levels of TSH and
caused by hypothalamic or pituitary dysfunction Ant. pituitary
is the problem
o Hyperthyroidism – overactive, thin hair, exophthalmos
(eyes enlarged), enlarged thyroid, tachycardia, weight loss,
diarrhea, warm skin/sweaty palms, pretibial edema (Graves’
disease is most common form of hyperthyroidism). It is caused
by an autoimmune mechanism that stimulates the TSH
receptors on the thyroid gland.
o Hypoparathyroidism – defined by abnormally low PTH
levels, is caused by thyroid surgery, autoimmunity, or genetic
mechanisms.
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
o Hyperparathyroidism – can be primary/secondary/tertiary, characterized by
greater than normal secretion of parathyroid hormone (PTH). Leads to
neuromuscular symptoms, bone damage, and renal stones.
o Hyperaldosteronism – characterized by excessive adrenal secretion of
aldosterone.
▪
Primary hyperaldosteronism (Conn Syndrome) – caused by excessive
secretion of aldosterone from an abnormality of the adrenal cortex,
usually a single benign aldosterone-producing adrenal adenoma.
▪
Secondary hyperaldosteronism – results from an extra-adrenal stimulus of
aldosterone secretion, most often through the secretion of excess
angiotensin II in response to decreased circulating blood volume and
decreased delivery of blood to the kidneys.
o Cushing Syndrome – group of clinical symptoms of excessive level of cortisol.
o Cushing Disease – excessive anterior pituitary secretion of ACTH
o Addison Disease – primary adrenal insufficiency, too little cortisol. Crisis can
cause atrophy/destruction of adrenal gland. Crisis caused by stress via trauma,
surgery infection, dehydration, prolonged hospital stay, chronic alcoholism, etc.
Disease Focus: As relates to the hormonal and metabolic concepts
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
Cardiac:
● Structure and function of cardiac system; forward-flowing pump. Understand how
any impediment of flow affects blood flow and resulting complications.
● Heart: essentially 2 pumps, left and right heart. Pulmonary circulation (right),
systemic circulation (left)
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Blood vessels: arteries > capillaries > veins
Right heart: pumps blood to pulmonary artery, capillaries, and veins
Left heart pumps blood to rest of body
Heart valves: tricuspid, pulmonary, mitral, & aortic. Allow blood flow to go
forward, prevent blood from backing up.
Forward flowing pump: structures directing movement of blood through the
heart. Heart is a forward flowing pump.
Heart wall (endocardium, myocardium, and epicardium) and pericardial sac
(visceral and parietal) (pericardial tamponade D:)
Chordae tendineae and papillary muscles ensure proper valve functioning
Coronary circulation
▪ Right coronary artery (supplies RA and RV)
▪ Left coronary artery
LAD (widow maker) (left anterior descending artery) (supplies
ventricles, main force of LV, if occluded → no systemic circ. D:)
Left Circumflex artery (supplies LA and LV) (in the back)
▪ Coronary sinus, Anterior cardiac veins, and Venae cordis minimae drain
deoxygenated blood back into RA
N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
● Cardiac cycle (Systole, diastole)
● Cycle = one contraction and one relaxation phase
● Systole – contraction phase
● Diastole – relaxation phase
● MAP—be able to calculate based on blood pressure values:
● MAP = (1) Systolic + (2) Diastolic / divide by 3
●
Ex: BP 100/48
● (1) 100 + (2)48 / 3 = 65
● Normal range: 70-110 mmHg
● Minimum to maintain tissue perfusion: ≥65!!!
● Cardiac conduction system—general pathway (more in later courses)
● Starts in SA (Sinoatrial) node in right atrium, “pacemaker”
● AV (Atrioventricular) node
● Bundle of His
● Right bundle branch > Left bundle branch
● Purkinje fibers
●
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SA Node (60-100 bpm) → AV Node (40-60) → R and L bundle branches → Purkinje
fibers (20-40)
N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
● Cardiac output (CO) formula:
● CO=Heart Rate x stroke volume (SV)
● Normal CO = 5 - 8 L/min
● Stroke volume = (preload, afterload, and contractility) (average is 60-100 cc)
● Heart rate = 60-100 bpm
● Determinants of cardiac output: HR slower = greater filling time, HR faster =
decreased filling time
● Preload: volume (pressure) in ventricles just before systole. Volume of blood in
ventricles at end of diastole. Increased in hypervolemia regurgitation of cardiac
valves heart failure
● Contractility: force of contraction
● Afterload: resistance from the aorta that left ventricle must overcome to get
blood to the rest of the body. Resistance left ventricle must overcome to circulate
blood. Increased afterload = increased cardiac workload.
● Frank-Starling law: Effect on cardiac output formula (preload and contractility)
● Force of contraction: The greater the stretch on Ventricles (volume) the greater
the FORCE of contraction
● Increase preload (volume) increase stretch of ventricle increase force of
contraction
● Compare and contrast the structure and function of arteries, veins, and capillaries.
● Arteries – thick-walled, pulsating blood vessel transporting blood away from the
heart, arteries carry oxygenated blood.
● Veins – thin walled with more fibrous connective and have a larger diameter
compared to arteries
● Capillaries – composed solely of a layer of endothelial cells surrounded by a
basement membrane. Their thin walls and unique structure make possible the
rapid exchange of water; small soluble molecules; some larger molecules, such as
albumin; and cells of the innate and adaptive components of the immune system
between the blood and the interstitial fluid.
● Role of the endothelium (generally)
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
●
●
●
●
●
●
● May be considered separate endocrine organ
● Lining of blood vessels
● Functions: substance transport to cells, coagulation, anti-thrombogenesis (stops
clots being formed), fibrinolysis (breaks clots), immune system, tissue & vessel
growth, wound healing, vasomotion, affects afterload and tissue perfusion
Discuss the function of the RAAS system in regulating blood pressure.
● Renin-Angiotensin-Aldosterone System – system contributes to systemic
vasoconstriction, renal salt and water retention, and remodeling of blood vessels,
kidney, and the heart. Pathophysiologic mechanisms include overactivity of the
sympathetic nervous system; overactivity of the renin-angiotensin-aldosterone
system; sodium and water retention by the kidneys; hormonal inhibition of
sodium-potassium transport across cell walls
● Also ADH, EP
● ANH/BNP ↓BP
Triad of Virchow (3 components)
● 1) injury to the blood vessel endothelium
● 2) abnormalities of blood flow
● 3) hypercoagulability of the blood
Discuss the differences between primary and secondary hypertension.
● HTN results from sustained increase in peripheral resistance and/or an increase
in circulating volume.
● Primary (essential): cause unknown, >90%, complex, genetic/environmental
factors. 1. SNS stimulation, 2. Overactivity of the RAAS, 3. Inflammation, 4.
Obesity
● Secondary: <10%, cause by an underlying disease process or med
▪ Renal disease, adrenocortical tumors, pheochromocytoma
Thrombus vs. embolus (major underlying causes)
● Thrombus – blood clot, attached. These conditions include those in which there is
intimal irritation or roughening (such as in surgical procedures and trauma),
inflammation, infection, low intravascular volume and pressures, or obstructions
that cause blood stasis and pooling within the vessels.
● Embolus – blood clot, traveling (can be air bubble, fluid, fat). Most emboli arise
from venous or arterial thrombi and travel in the bloodstream until they reach a
vessel through which they cannot pass.
Risk factors for atherosclerosis and the progression to myocardial infarction.
● Arteriosclerosis – thickening and hardening of vessel wall
● Atherosclerosis – formation of plaque. Leading cause of CAD & CV Disease
● Risk factors: hypertension, DM, increased levels of low-density lipoprotein,
decreased levels of high-density lipoprotein, autoimmunity
Compare and contrast the acute coronary syndromes.
● Caused by persistent ischemia or the complete occlusion of a coronary arteries.
When there is sudden coronary obstruction caused by thrombus formation over a
ruptured atherosclerotic plaque, acute coronary syndromes result.
▪ Unstable angina – reversible form of acute coronary syndromes
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
▪
Myocardial infarction – results when there is prolonged ischemia causing
irreversible damage to the heart muscle (non-STEMI vs STEMI). STEMI is
worse
▪ Sustained ischemia
▪ Myocardial inflammation and necrosis
● Valvular dysfunction (Location and effect on Cardiac output and blood flow)
● Stenosis: prevents forward blood flow
● Regurgitation: allows backward blood flow
● Define dysrhythmia:
● Abnormal change in HR or rhythm, can affect cardiac output
● Too fast/slow, interrupted, chaotic, ex: atrial fibrillation
● Compare left and right heart failure, including causation, manifestations.
● Failure of one side affects the other :(
● Where does fluid back up, what system precedes it?
● Left heart failure – usually a systolic pump failure (left ventricle failure).
Forward movement of blood from heart to system (body) is impeded, fluid backs
into the lungs, “congestive heart failure. Left sided heart failure can cause right
sided heart failure.
▪ Causes: MI, myocarditis, cardiomyopathies, increased ischemia,
increased workload, HTN, high afterload.
▪ *Clinical: paroxysmal nocturnal dyspnea, elevated pulmonary capillary
wedge pressure, pulmonary congestion. Restlessness, confusion,
orthopnea, tachycardia. Pulmonary edema can be caused by left
ventricular heart failure that can be heard on inspiration.
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
● Right heart failure – cannot move blood from periphery to lungs, causes right
heart failure, biventricular heart failure, increased pressure in pulmonary artery
to right ventricle, isolated right heart failure.
▪ Cause: isolated right heart failure, left to right cardiac shunt, chronic
lung disease, lung infections, inflammation, injury. Congestion in systemic
circulation results: peripheral dependent edema, lower extremities, liver
& spleen (hepatosplenomegaly), GI tract & peritoneal area.
▪ *Clinical: fatigue, ascites, enlarged liver and spleen, distended jugular
veins, dependent edema, may be secondary to chronic pulmonary
problems.
● Shock—General definition and the underlying cause of each major type
● Hypovolemic – volume loss, hemorrhagic
● Cardiogenic – heart not pumping effectively
● Distributive – septic, neurogenic, anaphylactic
● Obstructive – major obstruction of blood flow
● Exemplar conditions:
● DVT – Deep Venous Thrombosis, occurs primarily in the lower extremity.
● Hypertension – sustained increase in peripheral resistance and/or an increase in
circulating volume. Characteristics associated with development: over activation
of RAAS, insulin resistance, high SNS stimulation, high dietary sodium intake,
obesity.
● Myocardial Infarction – irreversible myocardial damage, due to prolonged
ischemia, effects on the body depend on location and size of damage.
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N3309 Exam 2: Key Concepts
Important Concepts taken from Objectives: Be able to APPLY these to patient situations
● Valvular stenosis – valve between the lower left heart chamber and the body's
main artery (aorta) is narrowed and doesn't open fully.
● Regurgitation – valve doesn’t fully close
● Heart Failure – when the heart is unable to generate an adequate cardiac output,
causing inadequate perfusion of tissues, or increased diastolic filling pressure of
the left ventricle, or both, so that pulmonary capillary pressures are increased.
● Shock – cardiovascular system fails to provide adequate tissue perfusion and
leads to decreased oxygen delivery, decreased glycose delivery. Prolonged lack of
tissue perfusion leads to cell/tissue death. Multi-organ failure. Death.
Disease Focus: Underlying pathophysiology as relates to cardiovascular blood flow along with
effects on hemodynamics and tissue perfusion
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