Flashcards
Jan 20 monday
Cards in this deck (106)
- 1Serum Albumin MAJOR protein in plasmaSynthesized in Liver
High Negative Charge (Prevents Excretion in Urine)
Maintains Oncotic Pressure (Therapeutically Used to Treat Burn Patients).
11 Distinct Hydrophobic Pockets (Permits Function as Carrier Protein)
Antioxidant Protein
(Binds Metals and Contains Reactive Groups to Detoxify Reactive Oxygen Species)
Transports Nitric Oxide (SNO; Vasodilation) - 2α1-antitrypsin (serpin):serine protease inhibitor with protective role during inflammation
inactivation by cigarette smoke (oxidation of Met358) can result in activation of serine protease subfamily members (i.e., elastase activity) that contributes to emphysema and COPD - 3α1-antichymotrypsin (serpin):serine protease inhibitor with protective role during inflammation.
- 4α1-acid glycoprotein (orosomucoid)carries basic or lipophilic compounds.
- 5Lipoproteins:Class of proteins that enable fats to be transported to adipocytes, muscle, and liver in blood stream (via chylomicrons, HDL, LDL, VLDL).
- 6serum amyloid AComponent of high-density lipoproteins (HDL; mediates transport of cholesterol).
- 7α2-macroglobulininhibits ALL classes of proteases, including those involved in coagulation (e.g., thrombin) and fibrinolysis (e.g., plasmin, kallikren)
- 8α2-antiplasminserpin responsible for inactivating plasmin (fibrinolysis)
- 9Protein C:zymogen that upon activation (proteolysis) inactivates blood clotting (FVa and FVIIIa) and activates fibrinolysis (plasmin).
- 10Ceruloplasminmajor copper carrying protein
- 11Thyroxine-binding globulin (TBG):binds thyroid hormones T3 and T4 (along with transthyretin and albumin).
- 12Haptoglobin:binds free hemoglobin for removal by spleen. Used to monitor for hemolytic anemia.
- 13Reninprotease responsible for cleavage of angiotensinogen to form angiotensin.
- 14Angiotensin:10 amino acid peptide hormone responsible for elevating blood pressure (through vasoconstriction).
- 15Transferrin:high-affinity iron binding protein (2 iron binding sites) that transports iron through the body.
- 16β2-macroglobulin (B2M):binds and activates membrane receptor (human hemochromatosis protein) to regulate iron transport by altering association of transferrin with transferrin receptor.
- 17Angiostatin:angiogenesis inhibitor (blocks growth of new blood vessels); under study as anticancer compound.
- 18Plasminogen:zymogen that upon activation (proteolysis) degrades fibrin (fibrinolysis) to clear blood clots.
- 19Protein BiomarkersPredictive biomarkers are often related to the change in abundance of particular proteins that provide measurable indicators of the severity or presence of a disease state, and responsiveness to treatment.
2 types
Classical biomarkers
Mechanistic biomarkers - 20Classical biomarkersin plasma indicate presence of disease but do not discern severity
Antibodies (e.g., autoimmune disease or infectious disease exposure)
Cellular proteins (e.g., organ function, such as alkaline phosphatase in liver or cardiac troponin in heart) - 21Mechanistic biomarkersprovide information of disease severity and responsiveness to drugs (e.g., may include cytokines related to toxicity of treatments).
- 22Plasma Proteinstransporters of lipids, hormones, vitamins, metals, immune surveillance, protease inhibitors, complement, clotting proteins.
- 23Buffy Coat:WBC (fight infection); platelets (blood coagulation); neutrophils (phagocytic cells); lymphocytes (B /T cells-adaptive immunity); monocytes (macrophages and dendritic cells); eosinophils and basophils (mediate inflammatory responses)
- 24Erythrocytes (RBC):Bags of hemoglobin (Hb) for transport of oxygen and carbon dioxide between tissues and lungs; nitric oxide for vascular tone. Hematocrit is the proportion of blood volume occupied by red blood cells (typically 3-fold Hb volume).
- 25Tissue Specific Cellular Proteins Can Serve as Biomarkers of Tissue DamageCardiac troponin
- 26Cardiac troponin(cTnI and cTnT); about 5% of cTn is free in cytosol and is released upon tissue damage.
- 27Key Serum Biomarkers to Diagnose Acute Myocardial InfarctionSpecific Markers:
CK-MB
Troponin-I
Troponin-T - 28Nonspecific Markers:LDH
Myoglobin
Troponin-T - 29ASpartate and ALanine aminoTransferases (transaminases) (AST & ALT):Primarily liver enzyme important for excretion of excess nitrogen through urea cycle.
Elevations in blood due to necrosis. - 30Aspartate AminotransferaseTransfers Collected Amino Groups on Glutamate to Aspartate in Liver
- 31Aspartateis Used as a Source of Amino Groups in the Urea Cycle During Amino Acid Catabolism.
- 32AmmoniaServes as the Direct Source of the Other Amino Group in the Urea Cycle.
Glutamate Does Not Directly Participate in Urea Cycle. - 33Alanine Aminotransferase in Musclemobilization of amino acid energy stores
Transfer of Glucose to Muscle
Transfer of Amino Groups to Liver - 34ALkaline Phosphatase (ALP):Serum ALP is primarily from liver and bone.
- 355’-nucleotidase (NTP):Hydrolyzes nucleoside-5’-phosphates. Similar to ALP, but elevations persist longer.
NTP increases due to obstructive jaundice and other liver disease.
Found in bone - 36Gamma-Glutamyl Transferase (GGT):Hydrolyzes glutathione enabling synthesis of reduced glutathione.
Broadly distributed, but increases in abundance in liver under conditions of oxidative stress.
Used to rule out bone disease (not found in bone). - 37Unconjugated BilirubinElevated levels indicate liver dysfunction [obstructive liver disease or loss of liver function (UDP-glucuronyltransferase activity; cirrhosis)].
- 38Blood Chemistry Tests / Basic Metabolic PanelPlasma is used to measure:
Glucose (electrochemical detection)
Calcium (calcium sensitive electrodes)
Electrolytes include sodium, potassium, bicarbonate, and chloride (electrochemical detection).
Blood urea nitrogen (BUN) is measured colorimetrically in plasma following NH3 production (urease enzyme) and phenol reaction.
Creatinine is measured colorimetrically following enzymatic conversion to creatine (by creatinase). Used to monitor kidney function. - 39Complete Blood Count MeasuresRed Blood Cells (RBCs), which carry hemoglobin
'
Overall number of white blood cells (with differential measures different types of WBCs)
Platelets, which mediate clotting
Hemoglobin (Hb), which carries oxygen
Hematocrit (how much space RBCs occupy in blood)
Mean Corpuscular Volume (MCV) ad mean platelet volume (MPV), which measures the average size of RBCs and platelets. - 40Anemias Classification:Microcytic
Macrocytic
Normocytic - 41Microcytic= Iron Deficiencies and Thalassemias (insufficient globin).
- 42MacrocyticB12 and/or Folate Deficiencies.
- 43NormocyticDecreased RBCs due to Bone Marrow Failure; Bleeding
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- 47Blood Vascular Sys.
- 48Lymphatic Vascular Sys..
- 49Generalized Vessel (art, vein, m=lymoh)Tunica Intima (endothelium)
Tunica Media
Tunica Adventitia - 50Virtually all vessels are lined bya simple squamous epithelium called an endothelium; this includes arteries, capillaries, veins, and lymphatic vessels.
- 51large Arteries> 1cm
Elastic, Conducting
T. Media: 40-60 layers, smooth muscle cells
e.g., aorta, subclavian, femoral, etc - 52tunica mediais filled with elastic fibers, manufactured by the smooth muscle cells there.
- 53medium aryeriesMuscular, Distributing
T. Media: 25-40 layers, smooth muscle cells
e.g., radial, dorsal scapular, intestinal AA, posterior tibial, etc.) - 54Medium arteryAt the bottom of the intima is a narrow but conspicuous internal elastic lamina.
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- 61small artery0.1 - 2 mm
T. Media: 4-24 layers, smooth muscle cells
Muscular branches and arteries for terminal distribution - 62Arterioles10 - 100 µm
T. Media: 1-3 layers, smooth muscle cells
Found deep within tissues, supply capillary beds - 63CAPILLARIEs4 - 10 µm
T. Media: NONE
Microscopic.
A capillary consists pretty much of an endothelium—nothing else.
Located within tissues only. Can only be visualized in the retina. - 64capillay typesContinuous
Fenestrated
Sinusoidal - 65VEINS - General Statements:Larger lumen than aa., not always round—often irregular
Thinner walls than companion artery.
Internal elastic membrane in medium & large vv.
Tunica boundaries often indistinct - 662 types VENULESPost-capillary
Muscular - 67Post-capillary10-50 µm
1 layer endothelium surrounded by pericytes
Structurally, little more than a capillary - 68Muscular50-100 µm
Endothelium + Subendothelium
1-2 layers smooth muscle cells in T. media - 69small/medium veins0.1 - 10 mm
Valves present to prevent backflow; note that valves are more abundant in the peripheral circulation
From very tiny veins to typical veins you see in the body—e.g., cephalic, posterior tibial, etc. - 70large veins> 1 cm
Ex.: Vena Cavae
T. Media reduced
T. Adventitia: longitudinal bundles of smooth muscle - 71VALVESValves are typically found in peripheral veins, e.g. in upper and lower extremities. In many areas the veins don’t have valves, e.g. venous sinuses of skull, hepatic portal veins, etc.
- 72Smooth MuscleSmall, spindle shaped cells
Typically surrounds hollow organs/cavities
Often electrically coupled and contract as single functional unit* (gap junctions)
Contains actin and myosin filaments
--But NOT arranged in sarcomeres
--No troponin
Dense bodies as cytoplasmic attachment points for thin filaments; protein plaques form membrane attachment points
--Instead of Z lines - 73Single-unit (unitary) smooth muscle:Contains gap junctions, so each muscle fiber does not need to be innervated, as the electrical signal to contract can move between cells (like cardiac muscle)
Named because all the connected smooth muscle cells contract together, like they were a single unit/cell.
Is the most common and will be mostly what we talk about associated with the peripheral circulatory system
Vascular smooth muscle is a type of single-unit, or visceral, smooth muscle - 74Multi-unit smooth muscle:Each individual muscle cell must bind neurotransmitter in order to induce contraction and each muscle cell acts independent of the others around it.
Independent contraction allows finer control of the process smooth muscle is controlling - 75There are three major pathways (that are not mutually exclusive) that may allow for an increase in cytoplasmic calcium concentration.1. Ca influx from the ECF through voltage-gated, L-type Ca channels
2. Ca release from the SR – either via calcium-induced calcium release or an IP3-mediated process (via activation of a plasma membrane G-protein coupled receptor binding of hormone, paracrine or neurotransmitter)
3. Ca influx from the ECF through non-voltage-gated Ca channels. These Ca channels are opened in response to stimuli other than changes in membrane potential. These can include stretch activated calcium channels and ligand-gated calcium channels.
----Channel-mediated Ca++ influx from the ECF can also depolarize the membrane potential - 76Calcium Regulation of Contraction At the level of myosinIntracellular [Ca2+] increase when Ca2+ enters cell or is released from SR (doesnt matter the source of Ca)
Ca2+ binds to calmodulin (CaM)
Ca2+-CaM activates myosin light chain kinase (MLCK)
MLCK phosphorylates myosin light chains in the myosin heads and increases myosin ATPase activity
Active myosin creates cross-bridges allowing myosin to slide along actin, creating tension - 77Poiseuille’s Lawprovides a description of how flow is related to perfusion pressure, radius, length of the system the fluid is flowing through and the viscosity of the fluid.
It is analogous to Ohm’s law that describes the relationship between current (electron flow), voltage (the driving force or gradient) and resistance to flow. - 78Unitary (single unit) and some multi-unit smooth muscle cells produce action potentials somewhat similar to(but longer than) skeletal muscle
- 79Some smooth muscle produces prolonged action potentials with a plateau phase (like cardiac muscle) Some smooth muscles show a slow wave oscillation of their membrane potential with action potential-like “spikes” at the peak depolarizationOther types of smooth muscle do not generate all-or-none action potentials at all and contraction varies based on the amplitude of the graded voltage deflection; this is generally true for multi-unit smooth muscle
- 80When/if an action potential is developed in smooth muscle (usually in single-unit, visceral smooth muscle), the rapid depolarization upon reaching threshold (i.e., phase 0) tends to be carried bythe voltage-gated L-type Ca channel.
- 81Voltage-gated L-type calcium channels): L-type calcium channels open when the membrane potential depolarizes, either due to an action potential or a graded depolarization. Unitary smooth muscle cells are often electrically coupled (via gap junctions), so the depolarizing signal can enter from a neighboring cell.
- 82IP3-gated calcium channels in the SRThis is a plasma membrane G-protein coupled receptor process, and here the activated Gq-protein activates phospholipase C (PLC)
leading to the production of IP3 (see Kandpal ISOM signaling lecture)
IP3 diffuses to the SR and binds to a smooth muscle isoform of the RyR (ryanodine receptor) calcium-release channel.
Note that the calcium store of smooth muscle SR is much less extensive than cardiac or skeletal muscle. This process does not require a change in membrane potential (it is a non-voltage-dependent process). Depending on the type of smooth muscle and the organ system it is associated with, signals that operate through the GPCR/IP3 pathway include epinephrine, ACh and the paracrine endothelin. - 83Ligand-gated calcium channelsA plasma membrane calcium channel is directly opened when a signal molecule (neurotransmitter, hormone or paracrine) binds to its receptor domain on the calcium channel
In a ligand-gated Ca channel, the channel protein has a receptor binding site and directly increases calcium influx. This process does not require a change in membrane potential (it is a non-voltage-dependent process). - 84Stretch-activated (mechanosensitive) cation channels:some types of smooth muscle respond to stretch by stimulating contraction. This may occur by either a stretch activate calcium channel or another type of cation (i.e., sodium) channel, that then depolarizes the membrane potential, and can also lead to the opening of the L-type Ca channel
- 85Calcium Regulation of Contraction at level ofmyosin, actin
- 86Smooth Muscle Regulation: ActinCaldesmon and calponin are two actin regulatory proteins that interact with tropomyosin
They act by inhibiting myosin ATPase activity - 87The inhibitory effect of calponin is removed bybinding to Ca-CaM
phosphorylation of calponin
Caldesmon is also regulated by phosphorylation - 88Pressure decreases froma high at peak systole in the left ventricle/aorta to a low in the vena cavae/right ventricle during diastole
- 89Pressure decreases at each level of the circulatory system,from the large arteries ---- smaller arteries ---- arterioles --- capillaries ---- venules --- veins
- 90the lower the pressure gradiat the lower theresistance to flow
- 91The rate at which blood flows, Q (through the whole cardiovascular system or through a vessel) is governed by two factors:The driving force is the pressure gradient, delta P. Delta P = Pin - Pout
The resistance (R) of the system (or vessel) to flow - 92The rate of blood flow (Q) is directly proportional to the delta P and indirectly (inversely) proportional to the resistance to flow: Q = delta P / R..
- 93How the body can influence resistance:Change the radius (or diameter, as diameter = 2 x radius) of the blood vessels. Vasoconstriction/relaxation is very common and one of the major ways in which blood flow and blood pressure are regulated.
Length of the blood vessels: not a factor on an acute basis, but does have effects. Morphologically, the length of some vessels can be important in affecting the pressure drop of blood flow through them (i.e., the renal arteries are short and wide, keeps pressure high).
Viscosity: refers to the “thickness” or “stickiness” of the fluid, the thicker it is, the harder it is to flow through a tube (think syrup vs water). The density of red blood cells (hematocrit) affects the viscosity of blood. Anemia decreases viscosity; elevated hematocrit (% of blood volume taken up by RBC) increases viscosity [you can see this with blood doping in athletes] - 94Changing the radius of blood vessels, especially at the level ofarterioles, is a key mechanism the body uses to control blood flow
- 95Rthe total peripheral resistance (TPR) or systemic vascular resistance (SVR) and represents the sum of all the resistances in series
- 96Resistances in series are additive and contribute to the total pressure drop in a “system”. Hence, the pressure in the blood vessels falls (drops) from the ventricles to the atria (LV RA and RV LA) as both the systemic and pulmonary circulations are “in series”. Note that the flow rate (Q) is the same at each level, all along the system, in spite of resistance changes, because pressure falls proportionally to resistance (the greater the R, the greater the delta P) within each segment. For example, the total flow through the aorta = total flow through the sum of the large arteries = total flow through all the capillaries, etc..
- 97Parallel ResistanceThe total resistance in a parallel circuit is less than any of the individual resistances
- 98series reisistanceThe total resistance in a series circuit is greater than any of the individual resistances
- 99Total resistance decreases as the number of branches increases, and the total resistance would increase as the total number of branches decreased..
- 100With the occlusion of a vessel (decreasing the number of branches), for example,you would then see an increase in resistance, and you would also see an increase in the deltaP in order to keep flow (Q) constant.
- 101Flow rate (Qis volume per unit time (i.e., liters per minute)
: how much volume of a fluid (ie blood) passes a given point per unit time. Always volume per unit time. [example: how many cars are passing under a freeway overpass per unit time] - 102Flow velocity (V)is distance per unit time (i.e., cm per second)
the distance a fixed volume/particle travels per unit time; how far will a single blood cell go over a period of time - 103At a constant flow rate, velocity increases as the diameter of the tube decreasesVelocity is inversely proportional to area
- 104As the diameter of a system decreases, the velocity of flowincreases
- 105If you have multiple small diameter tubes in parallel, while the cross-sectional area of each individual tube is small, in sum total, they can have a verylarge total x-sectional area
- 106Thus velocity through any individual tube in a system with a large x-sectional area is very slow.
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- Flashcards on Jan 20 monday, created by Shylla T on 20/01/2020.
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- Shylla T · Jan 2020
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- Jan 21, 2020
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