FINAL EXAM Flashcards
where are platelets derived from?
megakaryocytes in bone marrow
how long do platelets last?
8-9 days in circulation
where is platelts stored and how much
1/3 stored in the spleen and released when needed
what stimulates platelet production
thrombopoietin
where are platelets made
liver, kidney, smooth muscle, bone marrow
do platelets have a nucleus?
no
what do a-granules contain?
fibronogen, coagulation factors, plasminogen, PAF and PDGFs
what do δ-granules contain?
ADP, ATP, Ca2+, serotonin and histamine
All but which of the following are true about platelets?
A. An enzyme called erythropoietin stimulates their
production. B. They are made from megakaryocytes. C. They originate from the bone marrow. D. They are stored in the spleen
A
what do plasma proteins circulate as
inactive procoagulation factors
where are plasma proteins synthesised
most are by the liver
when is ca2+ (factor IV) required?
in all but the first two clotting steps
steps of clot dissolution
Antithrombin III, proteins C & S, plasminogen –> plasmin
(digests fibrin strands)
The endothelial surface prevents?
platelets & plasma
coagulation factors from interacting with the underlying
thrombogenic subendothelial ECM
Healthy, intact endothelial cells normally produce several
substances that prevent platelet adhesion & aggregation
- PGI2
– NO
– ADPase
– tPA
stages of hemostasis
1) Vessel spasm
2) Formation of the platelet plug
3) Blood coagulation or development of an insoluble fibrin
clot
4) Clot retraction
5) Clot dissolution
stage 1 of hemostasis
- MOI: Local and
humoral
mechanisms * Transient (<1 min) - Vascular smooth
muscle contracts
to decrease blood flow - Local neural
reflexes & humoral
factors (TXA2
from
platelets)
contribute to
vasoconstriction
stage 2 of hemostasis
- vWF (from endothelium)
causes adhesion of
platelets to exposed
collagen of vessel wall - Platelets become
activated & release ADP
& TXA
2
which causes
platelet aggregation &
formation of a plug
(therefore aspirin acts as a platelet aggregation inhibitor)
stage 2 hemostasis
- Insoluble fibrin threads hold the clot together
- Anticoagulants such as heparin (mast cells) act to prevent
excessive fibrin formation (ie. decrease clotting)
stage 4 hemostasis
- Within 20-60 mins
- Actin & myosin in
platelets contract to
squeeze serum from
the clot & join the
edges of the broken
vessel - Failure of clot
retraction indicative
of a low platelet
count
stage 5 hemostasis
- “Fibrinolysis”: Allows
blood flow to be re-
established & tissue
repair to take place;
strands of the clot are
dissolved - Plasminogen activators
such as tPA & uPA
cause formation of
plasmin, which digests
the fibrin strands of the
clot
what is fibrinolysis
- “Fibrinolysis”: Allows
blood flow to be re-
established & tissue
repair to take place;
strands of the clot are
dissolved
hypercoagulability
Conditions that predispose to thrombosis & blood vessel
occlusion
two forms of hypercoagulability
- increase platelet function
- increase clotting acitivity
increase platelet function
- increase platelet function
– increase platelet # (thrombocytosis)
– Blood flow disturbances Caused by
– Endothelial damage atherosclerosis
– Platelet aggregation
(last 3 are caused by atherosclerosis)
increase clotting activity
– increase procoagulation factors
– decrease anticoagulation factor
1.inherited or
2. aquired by prolonged bed rest, smoking, obesity etc
true or false
Hypercoagulability states increase the risk of thrombus
formation.
true
decrease in platelet levels (thrombocytopenia)
- decrease production in bone marrow
- increase destruction due to antiplatelet Ab’s
- Platelets used up in forming excessive clots
decrease platelet FUNCTION (thrombocytopathia)
- Inherited (vWF disease) or acquired (aspirin &
NSAID use which decreases TXA2
production)
Coagulation disorders (2)
– Inherited: eg. vWF disease (decrease vWF) or Hemophilia A
(decrease factor VIII)
– Acquired: liver disease or vit K deficiency
COX-1 catalyzes
production of thromboxane A2
COX-2 catalyzes
production of prostaglandins
what inhibits COX-1 and COX-2?
Aspirin and NSAIDs
why is aspirin used as a blood thinner
prevent blood cells called platelets from clumping together to form a clot
why is “blood thinner” not the best description
they don’t actually make blood thinner
What is the effect of von Willebrand disease on the
platelets?
decreased platelet adhesion
true or false
Platelet disorders are likely to lead to excessive bleeding
true
Spectrin/ankyrin network
imparts
both elasticity &
stability to the RBC
Adult (HbA) vs. fetal Hb
(HbF) forms
HbF has a higher affinity
for O2
RBCs rely upon what to make ATP
anaerobic
glycolysis to make ATP
How many molecules of oxygen can be carried by one
molecule of hemoglobin?
Four (each hemo has 2 alpha and 2 gamma molecules)
what does affects the rate at which Hb is made?
depends on Fe availability
how much Fe is found in Hb
~65%
how much Fe is stored in a different place and where?
~15-30% stored in liver and reticulo-endotherlial cells of bone marrow
transferrin
Fe transporter in plasma
Ferritin
a protein-Fe storage Complex (mainly liver)
- serum ferritin levels = index of body iron stores
RBC lifespan
~ 120 days
bilirubin
a yellowish pigment that is made during the breakdown of red blood cells
jaundice
if RBC destruction >
ability of liver to remove bilirubin
from blood
Haptoglobin
a protein made by your liver. and will bind the excess plasma Hb
If overwhelmed
(water soluble)
hemoglobinemia and/or
hemoglobinuria can result
hemoglobinemia
a medical condition in which there is an excess of hemoglobin in the blood plasma
hemoglobinuria
if the level of hemoglobin in the blood rises too high, then hemoglobin begins to appear in the urine.
Why would someone with renal failure develop
anemia
because there is a lack of EPO
MCV (mean corpuscular volume)
decrease with microcytic & increase with macrocytic anemias
MCHV (mean corpuscular hemoglobin concentration)
Normochromic & hypochromic anemias
microcytic and macrocytic
Microcytic cells are smaller than normal size, especially in the setting of iron-deficient anemia and anemia of chronic disease. Macrocytic anemia is a type of anemia where the average red blood cell volume is larger than normal
Normochromic & hypochromic
Erythrocytes containing the normal amount of hemoglobin (normal MCHC) are called normochromic. When the MCHC is abnormally low they are called hypochromic
Red blood cells (erythrocytes) are made in the ________
and destroyed in the _________.
bone marrow, spleen
Iron Deficiency anemia
Common worldwide cause of
anemia affecting persons of all ages
* Chronic blood loss or deficient diet
* decrease Hb and Hct
* decrease serum Fe and ferritin
* Hypochromic and microcytic
erythrocytes
* Poikilocytosis (irregular shape)
* Anisocytosis (irregular size)
* Depending on severity: pallor,
fatigue, dyspnea, tachycardia
Megaloblastic Anemia
caused by decreased DNA synthesis:
– Vitamin B12
and folic acid deficiencies
(both are needed for DNA synthesis) – Impaired DNA synthesis –> enlarged
red cells
– RBCs are large, often with oval shape
Aplastic Anemia
Aplastic due to disorder of pluripotent BM stem cells
– Usually leads to decreased RBCs, WBCs & platelets
– Causes: radiation, chemotherapy, chemicals, toxins,immunological problems, idiopathic.
– Tx: blood transfusions, bone marrow transplant
Which type of deficiency is caused by pernicious anemia?
vitamin B12
what is polycythemia
increase RBC count and Hct >50%
relative polycythemia
decreased PV but without an increase in RBCs
- dehydration, diuretic use, diarrhea etc
- corrected by increasing vascular fluid volume
absolute polycythemia
increase RBC mass
two types of absolute polycythemia
Primary: neoplastic (polycythemia vera)
- increase RBCs, WBCs and platelets
-causes blood hyperviscosity
Secondary : chronically increased [EPO]
- hypoxia related
Taylor has all the classic signs of anemia – fatigue, lack of concentration, and higher than normal resting and submaximal heart rate. She mentions one week ago she suffered a physical trauma and lost significant blood (although not enough to require a transfusion). You feel confident that her anemia is due to acute blood loss. What initial lab findings would confirm your suspicions?
a) Microcytic and hypochromic RBCs. Normal reticulocyte count. b) Normocytic and normochromic RBCs. Slightly higher than
normal reticulocyte count. c) Microcytic and hypochromic RBCs. Slightly higher than normal
reticulocyte count.
d) Normocytic and normochromic RBCs. Normal reticulocyte count
b) Normocytic and normochromic RBCs. Slightly higher than
normal reticulocyte count.
Fast forward one month and Taylor is still anemic. This time her doctor is concerned that she may be developing an iron-deficiency anemia. What lab findings would assist in this diagnosis
a) Microcytic and hypochromic RBCs. Normal reticulocyte count. b) Normocytic and normochromic RBCs. Slightly higher than
normal reticulocyte count. c) Microcytic and hypochromic RBCs. Slightly higher than normal
reticulocyte count.
d) Normocytic and normochromic RBCs. Normal reticulocyte count
c) Microcytic and hypochromic RBCs. Slightly higher than normal
reticulocyte count.
antigens AKA immunogens
foreign substances that elicit specific responses
antibodies AKA immunoglobulins
made in response to the antigen
humoral response
principle defence against EXTRACELLULAR microbes and toxins
cell-mediated immunity
mediated by specific T lymphocytes and defends against INTRACELLULAR microbes (viruses)
MHC (aka HLA) molecules
membrane bound proteins that display peptides for
recognition by T cells. Involved in self-recognition & cell-to-cell communication
MHC molecules two classes
Two classes, closely related:
– MHC-I – recognized by CD8+ cytotoxic T-cells
– MHC-II – recognized by CD4+ helper T-cells
IgG:
circulates in body fluids, binding antigens
(most abundant)
IgA
found in secretions on mucous
membranes; prevents antigens from entering
the body
IgM
circulates in body fluids; has five units to
pull antigens together into clumps
IgD
found on the surface of B cells; acts as an
antigen receptor
IgE
found on mast cells in tissues; starts
inflammation; involved in allergy
T-lymphocytes:
Activate other T & B cells
– Control intracellular viral infections
– Reject foreign tissue grafts
immunity”
– Involved in delayed hypersensitivity rxns
“all cell mediated immunity”
Helper T cell (CD4+)
– “Master regulator” of immune system
– Recognize MHC II-Ag complexes
– Can themselves differentiate into
subpopulations (eg. TH1, TH2) with varying functions
Cytotoxic T cell (CD8+)
Kill virally infected or cancer cells by
recognizing MHC I-Ag complexes
Regulatory T Cell
Seem to play a role in suppressing excessive
immune responses
Active immunity
acquired through immunization or
actually having a disease
– Slower but provides longer lasting immunity
Passive Immunity
– transfer of protective antibodies
against an Ag (eg. in utero or breast milk, antiserum)
– Rapid but only short term protection
what is the immunoglobulin(s) that cross the placenta
IgG is the only class of immunoglobulins to cross the placenta * Largest amount of IgG crosses the placenta during the last weeks of
pregnancy
– Premature infants may be deficient
what does aging do to the immune response
Aging associated with decreased cell mediated & humoral
immunity
– increase infection susceptibility
– increase autoimmune & immune complex disorders – increase incidence of cancer
Innate AKA natural or native
early, rapid response
Adaptive AKA specific or acquired
Develops later,
but more effective
Innate immunity
- Always present, rapid
response - Attacks non-self microbes * Does not distinguish
between different microbes * Mechanisms include:
– Epithelial barriers
– Phagocytic leukocytes
(eg. neutrophils &
macrophages)
– Specialized lymphocytes
(eg. NK cells)
– Plasma proteins (eg.
complement)
Adaptive Immunity
- Attacks specific microbes
(antigens or Ag) - Longer response time,
develops after exposure
to specific Ag - Immunological “memory” * Mechanisms include:
– Humoral immunity –>
antibodies from B cells
(blood & mucosal fluid)
– Cell-mediated immunity
–>T cells
True or false?
A vaccination is an example of adaptive immunity
True
where do B adn T cells mature?
B” cells mature in Bone marrow – “T” cells mature in the Thymus gland
chemokines
attract and activate WBCs
colony-stimulating factors
stimulate bone
marrow stem cells to divide and mature
– GM-CSF, G-CSF, M-CS
If an epithelial barrier is breached, the
early response cell is the
neutrophil
NK cells can directly
kill abnormal cells
opsonins
- various soluble proteins that “tag” microorganisms
for phagocyte recognition - Once the opsonin-coated microbe attaches to a
complementary receptor on a phagocytic cell,
phagocytosis is activated
inflammatory cytokines
– eg. TNF-α, IL-1, IL-6, IL-12,
interferons & chemokines
* Produces chemotaxis of leukocytes, stimulates acute-
phase protein production, inhibits viral replication
true or false
lipids are insoluble in plasma
true
5 types of lipoproteins
- chylomicrons
- VLDL
3.IDL
4.LDL
5.HDL
what is Chylomicrons made out lof
80-90% triglycerides
2% protein
VLDL made of
55-65% triglycerides
10% cholesteral
5-10% protein
LDL made of
10% triglycerides
50% cholesterol
25% protein
HDL made of
5% triglycerides
20% cholesterol
50% protein
Apo(lipo)proteins:
– increase stability of LP
– Activate enzymes
involved in LP
metabolism
– Receptor recognition
in peripheral tissues
Apo(lipo)proteins exist in
two classes
– Exchangeable (eg.
apoA-I, apoC-II &
apoE)
– Nonexchangeable
(apoB-48, apoB-100)
exogenous intestinal pathway
– Involved in the transport
of dietary cholesterol & TGs from intestine to liver & other tissues (muscle, adipose tissue)
– In the form of
chylomicron
Endogenous hepatic pathway
– The processing of cholesterol & TGs by the liver and distribution to tissues
– In the form of VLDL, IDL
what are lipids absorbed from. the intestine as?
Dietary lipids are absorbed from intestine as chylomicrons (into lymphatic system & bloodstream)
Chylomicrons deliver what
(2)
(a) dietary cholesterol to the liver and (b) TGs to adipose tissue & muscle
what does the liver make and release
VLDL which delivers TGs to tissues
As VLDLs lose TGs, they become
IDLs
IDLs lose more TGs and become
LDLs
HDL carries ….
cholesterol from peripheral tissues back to liver (“reverse cholesterol transport”)
LDL
—low-density lipoproteins (“bad”)
– Lower density: decrease protein, increase cholesterol
– Transports cholesterol from the liver to tissues
– Can be oxidized and deposited on vessel walls
(triggers the atherosclerotic process)
HDL
- HDL—high-density lipoproteins (“good”)
– Higher density: increase protein, decrease cholesterol
– Transports cholesterol from tissues to the liver
– Facilitates the clearance of cholesterol from atheromatous plaques and transports it to the liver, where it may be excreted
hyperlipidemia
increase of any/all lipids and/or LPs in blood
– Primary (inherited): genetic basis
– Secondary (acquired): due to diabetes, thyroid/renal/liver
disease, Cushing syndrome, obesity, alcoholism, drugs
Hypercholesterolemia
increase in cholesterol in blood
– Primary: eg. familial hypercholesterolemia (mutation in LDL
receptor gene)
– Secondary due mainly to lifestyle factors (eg. obesity,
diabetes, sedentary lifestyle)
- High calorie diets increase production of VLDL –> increase LDL
- Excess cholesterol ingestion may decrease LDL receptor
synthesis, which decreases LDL removal from the blood
TC =
VLDL + LDL +
HDL
Statins
decrease or block the hepatic
synthesis of cholesterol thus
decrease LDL
* Also lower TG levels
Which vessel layer can “expand” or “contract” to
accommodate or adjust pressure within the vessel?
A. Tunica intima
B. Tunica media
C. Tunica externa
tunica media
skip
- Monocytes attach to the endothelium –>
macrophages - Macrophages release free radicals –>
oxidizes LDL (endothelial toxin) - Macrophages ingest oxidized LDL –>
become foam cells - WBCs, platelets, and vascular endothelium
release chemicals that promote plaque
formation - Plaques can block arteries or rupture &
cause a thrombus
atherosclerosis stage 1
Endothelial cell injury leading to adhesion of monocytes & platelets
atherosclerosis stage 2
Migration of inflammatory cells into the intima
– Monocytes transform into macrophages that begin to engulf
LDL
atherosclerosis stage 3
Lipid accumulation and smooth muscle cell proliferation
– Activated macrophages oxidize LDL (ROS release)
– Oxidized LDL is then aggressively ingested by macrophages
leading to foam cell formation – GFs also lead to proliferation of smooth muscle cells & increase ECM
atherosclerosis stage 4
Plaque formation
– Formation of a fibrous cap (smooth muscle cells & dense ECM) with
a cellular “shoulder” & a necrotic “core” (lipid laden foam cells & fatty debris)
– Rupture of an unstable cap can lead to bleeding or thrombotic
vessel occlusion
non- modifiable (atherosclerosis)
– Age, male gender, genetic disorders of lipid metabolism, family hx of premature CAD
Potentially modifiable (atherosclerosis)
– Smoking, obesity, hypertension, hyperlipidemia with increase LDL & decrease HDL, diabetes
no-traditional (atherosclerosis)
– Chronic inflammation eg. C-reactive protein (CRP)
–acute-phase protein for systemic inflammation
– increase lipoprotein (a) levels in blood (altered form of LDL that
contains apo-B-100)
manifestations of atherosclerosis in the heart
Heart –> stable angina or acute coronary
syndrome = myocardial infarction or unstable angina
manifestations of atherosclerosis in the aorta
aneurysm
manifestations of atherosclerosis in the brian
transient ischemic attack or cerebrovascular accident
manifestations of atherosclerosis in the legs
peripheral arterial disease
manifestations of atherosclerosis in the bowel
bowel infarction
What immediate threat do unstable plaques present
A. Clot formation will increase pressure in the vessel.
B. Plaque may lead to angina (chest pain).
C. Clots may break loose and block blood flow to key
organs.
D. All of the above constitute immediate threats
c
“True” vs. “false” aneurysms
Unlike a true aneurysm, a pseudoaneurysm does not contain any layer of the vessel wall. Instead, there is blood containment by a wall developed with the products of the clotting cascade.
what happens during SBP and DBP
SBP - ventricle contracts
DBP - ventricle relaxes
pulse pressure =
SBP-DBP
primary or essential hypertension
(no evidence of other diseases)
– ~90-95% of all cases (very common) – Genetics, ethnicity, age, diet, obesity, alcoholism
secondary hypertension
(results from another disease/disorder)
– Renal hypertension, adrenocortical hormone
disorders, pheochromocytoma, aortic coarctation,
oral contraceptives
target organ damage
is main concern (p.428)
– Kidneys, heart, eyes are particularly vulnerable but
all blood vessels may be affected
* Tx is lifestyle & pharmacologic:
– ACE inhibitors, diuretics, β-receptor inhibitors, Ca2+
channel blockers, etc
orthostatic/postural hypotension
- Abnormal drop in BP on
assumption of standing
position - Causes:
– Reduced BV: diuretic use,
vomiting, diarrhea
– Drug induced hypotension
(antihypertensives)
– Aging – Bed rest & immobility (decrease PV)
– ANS disorders
deep venous thrombosis
Presence of thrombus in a vein and
the accompanying inflammatory response
triad of thrombosis
– circulatory stasis + endothelial damage + hypercoagulability
why do clots tend to form in leg veins
because they are deep large veins
what are leg veins susceptible too?
blood
pooling and as venous return must
move against gravity, there is increase
chance of venous stasis
what do leg veins have a risk of?
Risk of pulmonary embolism
A patient takes a drug that is a sympathetic agonist. Which
of the following would you expect to occur
A. Increased heart rate and blood pressure
B. Increased heart rate and decreased blood pressure C. Decreased heart rate and increased blood pressure
D. Decreased heart rate and blood pressure
A
what is the most common cause of coronary artery disease (CAD)?
atherosclerosis
fixed atherosclerotic lesion
- Associated with stable
angina (if large enough
to cause ischemia) - Have thick fibrous caps
- Plaque usually partially
obstructs vessels - Do not tend to form clots
or emboli
vulnerable atherosclerotic lesion
- Associated with
unstable angina & MIs * Have thin fibrous caps * Plaque can rupture &
cause clot to form
– May completely/
incompletely occlude
artery – May break free &
become an embolus
acute coronary syndrome
Ranges from unstable ischemia to acute MI (NSTEMI or
STEMI)
ACS ECG changes can include
- ECG changes can include:
– T-wave inversion – ST-segment depression or elevation – Abnormal Q waves
ACS serum cardiac markers
- Serum cardiac markers (p.449)
– Proteins released from dead/necrotic heart cells
º Myoglobin, CK-MB, cardiac-specific TnI & TnT
ACS Why are T waves and the ST segment first to be involved?
(ST parT)
– ST segment
* Is usually a flat, isoelectric line and represents the early start of ventricular
repolarization
* “Current of injury” created between normal cells and ischemic cells causing
deviation in normally flat ST segment –> elevated or depressed ST segment
ACS Why are T waves and the ST segment first to be involved?
T PART
- Is usually upright in Lead II & represents ventricular repolarization * Ischemic cells no longer normally repolarize –> often inverted in Lead 2
ACS what about the abnormal Q waves
– Scar tissue due to a MI does not transmit electrical activity
– Ventricles may not depolarize normally leading to changes in Q waves
signs and symptoms of acute myocardial infarction
- Chest pain!
– Severe, crushing, constrictive OR like heartburn - SNS response
– GI distress, nausea, vomiting
– Tachycardia and vasoconstriction
– Anxiety, restlessness, feeling of “impending doom” - Hypotension and shock
– Weakness in the arms and legs
treatment of acute coronary syndromes
*O 2
* Drugs:
– Aspirin
– Nitrates
– Morphine
– Anticoagulants
– β-blockers
– ACE inhibitors * Reperfusion therapy
– Fibrinolytic drugs
– Stent insertion (PTCA)
– CABG surger
myocardial infarction recovery 3 zones of tissue damage
– Necrotic zone (replaced with scar tissue)
– Surrounding injured/hypoxic cell zone
– Ischemic outer zone
what is critical about Myocardial infarction recovery?
Timeliness of Tx is critical to re-establish blood flow &
limit damage! (20-40 mins)
what are the problems with the scar tissue in myocardial infarction
- Fibrous scar tissue lacks the contractile, elastic &
conductive properties of normal myocytes
– Complications are determined by extent/location of injury
chronic ischemic heart disease
- Imbalance in myocardial O
2
supply vs. demand due to:
– decrease blood supply (due to atherosclerosis or vasospasm)
–increase O2
demand (due to stress, exercise or cold)
3 classifications of chronic ischemic heart disease
- Chronic stable angina
- Silent myocardial
ischemia (no pain) - Variant (vasospastic or
Prinzmetal) angina
(CIHD) Stable angina
– fixed coronary obstruction that can occlude
blood flow
– Typical angina – Usually provoked by PA or stress and relieved by rest or nitroglycerin
CIHD - variant angina
– coronary artery spasm. Etiology not known, but endothelial dysfunction, hyperactive SNS, etc. may contribute
– Angina that occurs at rest or during night
CIHD - silent myocardial ischemia
– same causes as stable angina, but
anginal pain not experienced
– Ischemic episodes may be shorter and involve less myocardium – Defects in pain tolerance or pain transmission, or autonomic neuropathy
with sensory denervation
valvular heart disease 2 types of mechanical disruption
stenosis and regurgitation
stenosis
Valve will not open correctly
(valve narrowing)
– Harder to force blood through
– Will hear murmur of blood
shooting through the narrow
opening when the valve is open
regurgitation
Valve will not close
correctly
– Leaks when “closed”
– Will hear a murmur of blood
leaking back through when the
valve should be closed
valve disorder
- Most commonly
affect mitral & aortic
valves
If A/V valves leading
into the ventricles do
not work…?
mitral or tricuspid problems
if semilunar valves leading out of the ventricles do not work…?
aortic or pulmonary problems
mitral valve disorders
– Mitral valve stenosis
– Mitral valve
regurgitation – Mitral valve prolapse
(“floppy” valve)
aortic valve disorders
- aortic valve stenosis
- aortic valve regurgitation
cardiomyopathies
Disorders of heart muscle & myocardial performance
(mechanical or electrical in nature)
primary cardiomyopathy
(confined to myocardium)
– Genetic: HCM and arrhythmogenic right ventricular
dysplasia – Mixed: dilated and restrictive – Acquired: myocarditis (usually viral); peripartum and
Takotsubo cardiomyopathy
Secondary cardiomyopathy
(associated with other disease conditions) – Drugs, diabetes, alcoholism, muscular dystrophy,
autoimmune disorders & cancer treatment (radiation & drugs)
hypertrophic cardiomyopathy
Unexplained left ventricular hypertrophy due to an autosomal dominant disorder
hypertrophic cardiomyopathy more info
Contractile protein mutation –> weak myocytes
– Myocytes hypertrophy to compensate (esp. LV) – Paradoxical decrease in SV due to decrease diastolic filling
* Myocytes need more O2 and perform less efficiently
– Prone to heart failure and potentially SCD during exertion
– HCM is most common cause of SCD in young athletes
what is hypertrophic cardiomyopathy most common cause of?
most common cause of sudden cardiac death in young athletes
symptom of HCM
Dyspnea, chest pain & post
exertional syncope
diagnosis and treatment of hypertrophic cardiomyopathy
Diagnosis by 2Decho + ECG
- Tx: symptom management
– β-blockers – Ca2+ channel blockers
heart disease congenital disorder
– ~ 1 out of every 125 infants
– Weeks 3-8 after conception
– Contributing factors:
- Genetic and chromosomal
- Viruses
- Drugs
- Radiation
heart disease acquired disorders
- kawasaki disease
true or false
Chronic ischemic heart disease is more likely to result in
stable angina than acute coronary syndromes
true
true or false
Mitral valve regurgitation results in a diminished stroke
volume.
true - if the mitral valve doesnt close as it should, a portion of the stroke volume leaks back into the left atrium so it will decrease stroke volume
heart failure
Complex syndrome resulting from functional or structural
impairment of ventricular filling or ejection
heart failure can be caused by
– Pericardial disorders
– Myocardial disorders
– Endocardial disorders
– Valve problems
– Disorders of great vessels
– Metabolic abnormalities
which populations have a high cardiac reserve and who has the lowest \?
athletes have a high one ~5-6x at rest
heart failure pationts may reach theirs at rest
stroke volume equals
end diastolic volume - end systolic volume
ejection fraction =
sv - edv (~60% at rest in healthy person)
Q =
sv x hr
pre-load
= volume of blood entering/stretching the ventricle
frank starling mechanism
increase preload –> increase stroke volume
afterload
force that ventricle must generate
Systolic (HFrEF) or diastolic (HFpEF) failure
– Is the heart failing to pump? (EF <40%)
* Impaired contractility, valve problems or pressure issues
– or is it resisting filling from body/lungs? (EF >50%)
* Hypertension, constrictive pericarditis, HCM, aging, obesity , diabetes
L-sided or R-sided failure
– If LV fails, blood backs up in the pulmonary circulation
- Due to hypertension, acute MI (in LV) or valve problems
– If RV fails, blood backs up in the systemic circulation
- Due to LV failure, pulmonary hypertension, valve problems, MI (in RV) or cardiomyopathy
manifestations of heart failure
- Fluid retention/edema
– Due to increase capillary hydrostatic pressures * Respiratory mechanisms - Dyspnea
- Orthopnea
- Paroxysmal nocturnal dyspnea * Fatigue/exercise intolerance, weakness, cognitive impairment
– Due to decrease Q - Cachexia & malnutrition
– Tissue wasting due to decrease appetite & congestion of liver/GIT - Cyanosis
– Due to decrease SaO2 - Arrhythmias & SCD
– AF & VF
is edema consistent with left or right sided heart failure
r-sided
edema
Capillary fluid moves into alveoli
– The lung becomes stiffer
– Harder to inhale (increase work of breathing)
– Edema –> decrease gas exchange in alveoli –> decrease Sao2
– Crackles
– Frothy pink sputum possible (due to the blood in the capillaries)
treatment of heart failure
Lifestyle/counselling
– Individualized exercise training, Na+ & fluid restriction &
weight management
Pharmacological:
– Diuretics
* Promote loss of H2o & decrease volume overload (decreasing edema)
– ACE inhibitors
* Prevent angiotensin I –> angiotensin II
* Thus less vasoconstriction
* Also decrease aldosterone –> decrease Na+ & H2O retention
– β-adrenergic receptor blockers
* decrease SNS influence–> decrease workload of the heart –> decrease LV
true or false
The characteristic pink sputum produced in pulmonary
edema is tinged with blood
true
hypovolemic shock
Acute loss of
>15% BV,
causing
inadequate
filling of the
vascular
compartment
caused by:
– Whole blood
– Plasma
– ECF
– Dehydration
– Internal
bleeding
cardiogenic shock
The heart fails to pump blood adequately
– eg. acute MI, valve disorders, arrhythmia, cardiomyopathy
cardiogenic shock results in
– decrease Q –> decrease BP
– increased SNS response
– Peripheral vasoconstriction (but this increase TPR)
– Note increase workload on the heart can worsen heart failure
* Tx: treat underlying problem & decrease workload on heart
manifestation and tx for hypovolemic
– Thirst, increase HR, cool/clammy skin, decrease BP, oliguria, neurologic
changes, etc.
– Tx: correct/control underlying cause & improve tissue
perfusion, O2
admin
manifestations and tx for cardiogenic shock
– Consistent with end stage heart failure: cyanosis (lips, nail
beds, skin), decrease BP, decrease PP, oliguria, neurologic changes
– Tx: A delicate balance of increase Q, decrease myocardial O2 demand &
decrease myocardial blood flow
* Drugs which increase myocardial contractility w/o increasing HR (eg.
dopamine, dobutamine
normovolemic shock
normal blood volume
neurogenic shock
a condition in which you have trouble keeping your heart rate, blood pressure and temperature stable because of damage to your nervous system after a spinal cord injury
septic shock
a life-threatening condition that happens when your blood pressure drops to a dangerously low level after an infection
major complications of shock
- Acute lung injury/respiratory distress syndrome
- Acute renal failure
- GIT complications
- Disseminated intravascular coagulation
- Multiple organ dysfunction syndrome
Which type of shock is caused by low blood volume
A. Cardiogenic
B. Hypovolemic
C. Distributive
D. Septic
b. hypovolemic
hypoxemia
low levels of oxygen in the blood
HYPERCAPNIA
when you have too much carbon dioxide (CO2) in your blood
true or false
Both hypercapnia and hypoxemia will lead to respiratory
failure if untreated.
true
two types of bronchial asthma
atopic (extrinsic) asthma
non-atopic (intrinsic) asthma
atopic (extrinsic) asthma
asthma triggered by allergens like pollen, pets, and dust mites.
non atopic asthma
asthma that isn’t related to an allergy trigger like pollen or dust.
chronic obstructive airway diseases
chronic bronchitis
emphysema
cystic fibrosis
chronic bronchitis
overproduction and hypersecretion of mucus by goblet cells, which leads to worsening airflow obstruction by luminal obstruction of small airways, epithelial remodeling, and alteration of airway surface tension predisposing to collapse.
asthma
a chronic inflammatory disease of the airways
commonly appears before age 5
pathogenesis of asthma
Genetic predisposition (eg. Allergy or defects in bronchial endothelium)
✚
Environmental factors (ie. allergens, excessive hygiene, antibiotics from 0-2 yrs)
=
Predisposed to airway hyper-responsiveness
atopic (extrinsic) asthma triggers
*Pet hair or dander
*Dust
*Chemicals in the air or in food
*Mold
*Pollen
*Tobacco smoke
*NOTE: Aspirin and NSAIDS can be trigger
non atopic (intrinsic) asthma
*Respiratory infections
*Exercise
– (Warm ups are important!)
*Hyperventilation
*Cold air
*Inhaled irritants
*Aspirin and other NSAIDs
1st exposure to allergen
Immune response stimulates B lymphocytes to
produce IgE which binds to mast cells =
sensitized mast cells
2nd exposure to SAME allergen
– Early response: Allergen x-links with IgE’s on
mast cells = mast cells release histamine, leukotrienes, and inflammatory mediators
– Late response: Activated mast cells release
cytokines and cause WBCs like eosinophils to be
released = affect airways, eyes & nose
atopic asthma
- Type I hypersensitivity
– ie. rapid & IgE mediated - Allergen
–> Mast cells release inflammatory mediators - Cause acute early-response
within 10-20 mins
–> WBCs enter region and
release more inflammatory
mediators - Airway inflammation causes
late-phase response in 4-8 h
nonatopic asthma
Respiratory infections
– Epithelial damage, IgE production
- Exercise, hyperventilation, cold air
– Loss of heat and water may cause bronchospasm - Inhaled irritants
– Inflammation, vagal reflex - Aspirin and other NSAIDs
– Abnormal arachidonic acid metabolism
mild to moderate signs of asthma
- Cough with or without sputum production
- SOB that gets worse with exercise or activity
- Chest tightness
- Wheezing
severe signs and symptoms of asthma
- Anxiety/apprehension
- Severe SOB / no wheezing / inaudible breath sounds
- increase use of accessory muscles
diagnosis of asthma
– Careful history & physical exam
* Portable PEF meters can be useful – Spirometry (decrease FEV1.0/FVC
treatment of asthma
– “Quick relief” bronchodilator (usually β2-agonist)
– “Longer term” medications (eg. inhaled
corticosteroids) to decrease airway inflammation
– Identify allergens and reduce exposure
Which of the following occurs in asthma?
A. Airway inflammation
B. Bronchospasm
C. Decreased ability to clear mucous
D. All of the above
D
chronic obstructive pulmonary disease
- Group of disorders
characterized by chronic &
recurrent airflow obstruction
in the airways
– Usually progressive
emphysema
Loss of lung elasticity,
abnormal enlargement of
air spaces & destruction of
lung tissue
mechanisms of COPD
- Inflammation and fibrosis of the bronchial wall
- Hypertrophied mucous glands –> excess mucus
– Obstructed airflow - Loss of alveolar tissue
– decrease SA for gas exchange - Loss of elastic lung fibers
– Airway collapse, obstructed exhalation, air trapping
risk factors for COPD
- Hx of cigarette smoking or significant lifetime exposure
to secondhand smoke
– 85-90% of COPD patients have a hx of smoking - Hx of airway infections
- Hx of chronic asthma or bronchial hyper-responsiveness
- Environmental/occupational exposures to dusts and
chemicals
emphysema more in depth
Neutrophils in the alveoli
secrete trypsin
– increase neutrophil # due to
inhaled irritants can
damage alveoli
*α1-antitrypsin inactivates the trypsin before it can damage the alveoli
– A genetic defect in α1-
antitrypsin synthesis leads
to alveolar damage
chest wall in emphysema
- Destruction of lung
tissue & enlargement of
air spaces leads to:
– Loss of elasticity
– Airways collapse
during expiration
– Trapped air – Lung hyperinflation
(“barrel chest”)
– increase TLC
– Diaphragmatic
fatigue and acute
respiratory failure
chronic bronchitis more in depth
– increase # of goblet cells (mucus secretion)
– Mucus hypersecretion (hypertrophy of submucosal glands
in trachea & bronchi)
– Inflammatory infiltration & fibrosis of bronchiolar wall
how is chronic bronchitis diagnosed
Diagnosed by a chronic productive (sputum) cough for
>3 consecutive months in at least 2 consecutive years
* Common in middle-aged men
pink puffers
(usually emphysema)
– Pink = lack of cyanosis
–increase VE to maintain oxygen levels
– Dyspnea; increased ventilatory effort
– Use of accessory muscles; pursed-lip (“puffer”) breathing
blue bloaters
(usually bronchitis- increase in mucus
production)
– Cyanosis
– Fluid retention due to R sided heart failure (due to hypoxic
pulmonary vasoconstriction/hypertension) – Cannot increase respiration enough to maintain O2 levels
diagnosis of COPD
-medical history
- spirometry
- chest xray
treatment of COPD
– Depends on stage
– Smoking cessation
– Reduce risk of RTIs
– Meds (bronchodilators)
–O2 therapy
in a COPD client, exhalation is…?
inefficient and o2 levels in the lungs decrease
If blood goes through the lungs filled with stale air
– Blood will not pick up enough O2
(potentially leading
to hypoxemia)
– Blood might even pick up CO2 (potentially leading to
hypercapnia
Which chronic obstructive pulmonary disease primarily
affects the alveoli?
emphysema
pulmonary embolism etiology
- Blood borne substance lodges in branch
of pulmonary artery (eg. DVT)
– Causes reflex bronchoconstriction,
pulmonary hypertension & R heart strain
manifestations of pulmonary embolism
– Asymptomatic to breathlessness to death
– Massive embolus leads to sudden
collapse, severe chest pain, shock & LOC
diagnosis and treatment of pulmonary embolism
– Imaging, history, ECG
– Thrombolytic meds if life-threatening
– Anti-coagulants
two types of pulmonary hypertension
primary and secondary
primary pulmonary hypertension
(increase in pulmonary BP in absence of another condition)
º Rare & debilitating
º Blood vessel walls thicken and constrict; can lead to R heart failure, low CO, and death
secondary pulmonary hypertension
(increase in pulmonary BP
associated with other
cardiopulmonary conditions)
º increase of pulmonary venous pressure
(mitral valve disorders)
º increase pulmonary blood flow
(congenital heart diseases)
º Pulmonary vascular obstruction
º Hypoxemia
R-sided heart failure secondary to lung disease or
pulmonary hypertension
decrease lung ventilation leads to:
* Pulmonary vasoconstriction- increase workload on right
heart (RV)
* decrease oxygenation causes kidneys to release EPO –>
more RBCs made –> polycythemia (makes blood
more viscous) which increases workload on the heart
what is metabolic syndrome also known as
AKA “insulin resistance syndrome” or “syndrome X”
hyperglycemia
– Intra-abdominal (visceral) obesity
– increase blood triglyceride levels
– decrease HDL levels
– increase blood pressure
– Systemic inflammation
what do pancreatic acini secrete
digestive juices into the duodenum
alpha cells secreate
glucagon
beta cells secreate
insulin and amylin
delta cells secreate
somatostatin
what is each islet of langerhans composed of?
alpha, beta and delta cells
what increases insulin secretion?
increase in blood glucose
Insulin increase glucose uptake, use & storage:
1) increase Glycogenesis
2) increase Lipogenesis (glucose –> fat)
3) increase Protein synthesis
Insulin decrease
Insulin decrease :
1) decrease Glycogenolysis
2) decrease Lipolysis
3) decrease GNG (amino acids –> glucose)
how many chains does insulin have and where is it released from?
2 chains and beta cells
If someone lacks insulin, what happens to:
– Blood glucose levels?
– Blood amino acid levels?
– Blood pH?
– Intracellular fat levels?
– Intracellular protein levels?
– Cell growth?
– Blood glucose levels? INCREASE
– Blood amino acid levels? INCREASE
– Blood pH? DECREASE
– Intracellular fat levels? DECREASE
– Intracellular protein levels? DECREASE
– Cell growth? DECREASE
decrease blood glucose –>?
decrease blood glucose –> increase glucagon secretion
– increase blood amino acids also stimulate secretion
Amylin (islet amyloid polypeptide):
decrease glucose absorption in
the small intestine; decrease glucagon secretion
– Secreted by pancreatic β-cells
– Possible role in causing type 1 diabetes?
Somatostatin:
decrease GI activity; decrease glucagon & insulin secretion
– Secreted by pancreatic δ-cells
Gut derived hormones that increase insulin release (incretins)
GLP-1 & glucose dependent insulinotropic polypeptide
“Counterregulatory” hormones (antagonistic to insulin)
– Epinephrine
– Growth hormone
– Glucocorticoids (mainly cortisol)
diabetes mellitus
Group of metabolic diseases characterized by
hyperglycemia resulting from defects in insulin secretion,
insulin action, or both
Chronic hyperglycemia:
Long term damage/failure to
eyes, kidneys, nerves, heart & blood vessels
- T1: β-cell destruction –> absolute insulin deficiency
– 1A autoimmune (genetic + env. cause) or 1B idiopathic - T2: insulin resistance and/or relative insulin deficiency
- Other types:
– Genetic defects in β-cell function or insulin action
– Secondary to other diseases, drugs, or transplant - Gestational diabetes mellitus (GDM
pathogenesis of T2DM
Combination of genetic & lifestyle
factors?
– Esp. obesity & physical inactivity *
Insulin resistance leads to initial
hyperinsulinemia to keep blood glucose normal
* Relative insulin deficiency:
– Insulin resistance or inadequate
secretory response
* Absolute insulin deficiency:
– Destruction of the beta cells * Complex - pathogenesis not
completely understood
- Relative insulin deficiency:
– Insulin resistance or inadequate
absolute insulin deficiency:
– Destruction of the beta cells
T1 and T2 timeline
T1 sudden onset; T2 more insidious
the 3 polys
polyuria, polydipsia, polyphagia
polyuria
your body makes more pee than normal
polydipsia
excessive thirst
polyphagia
an abnormally strong, incessant sensation of hunger or desire to eat often leading to overeating
management for both type of DM
Diet (both)
- Exercise (both)
– Note increase risk of hypoglycemia - Oral medications (T2), eg:
– Metformin (biguanide) – Liraglutide (GLP-1 R agonist) - Insulin injections (T1 or T2)
– Short, intermediate and long acting types
– MDIs & CSII (insulin pump)
oral medications of T2 DM
eg:
– Metformin (biguanide)
– Liraglutide (GLP-1 R agonist)
Diabetic ketoacidosis
– Hyperglycemia + ketosis +
metabolic acidosis
– Reflects an insulin
deficiency (ie. more
common in T1)
hypoglycemia
excess insulin or insufficient food
Hyperglycemic hyperosmolar
state
–H2O is pulled out of body cells, incl. brain
How would hyperglycemia with ketoacidosis cause:
– Heavy breathing?
– Fruity smelling breath?
– Polyuria?
– Thirst?
– Dehydration?
– Heavy breathing? because of metabolic acidosis
– Fruity smelling breath? keto acids
– Polyuria? osmotic diuresis
– Thirst? water is moving out of cells
– Dehydration? polyuria and osmotic diuresis
DM chronic complications
Somatic:
* Sensory –> decrease perception &
hypersensitivity issues
- Motor –> balance deficits
– Autonomic (defects in vasomotor,
cardiac responses, bladder problems,
GIT problems, erectile problems)
nephropathies
renal failure
retinopathies
blindness
other chronic complications for DM
Macrovascular complications
– increase atherosclerosis, CAD, CVD & PVD
* Foot ulcers due to neuropathy
* Infections
Which of the following is a complication of diabetes
mellitus?
A. Nephropathy
B. Retinopathy
C. Neuropathy
D. All of the above
D. all of the above
repair/regeneration of muscle occurs due to the presense of?
muscle satellite cells
ossification
conversion of fibrocartilaginous cartilage to bone
rheumatoid factor
antibody against IgG fragments in most patients
