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1. Karyolysis- Nuclear dissolution and lysis of chromatin from the action of hydrolytic enzymes.
2. Pyknosis- The nucleus shrinks and becomes a small, dense massof genetic material.
3. Karyorrhexis- Fragmentation of the nucleus into smaller particles (nuclear dust)
Fast, slow and intermediate twitch type ms can be identified by histochemistry. In any muscle, there is a mix of slow and fast fibers. Motor units containing slow fibers will be recruited first to power normal contractions. Fast fibers help out, especially when forceful contraction is required.
More slow fiber- Marathon runner, swimmer
More fast fiber- sprinters and jumpers, a little bit with avg man and wt lifter.
Specific cell or tissue is the target of an immune response. Environmental antigents (eg drugs or their metabolites) may bind to plasma membranes of specific cells; especially erythrocytes and platelets.
5 mechanisms: 1. Cells destroyed by antigen or complement 2. Cell destruction through phagocytosis 3. Soluble antigen may enter circulation and deposit on tissues 4. Antibody dependent cell mediated cell toxicity 5. Causes target cell malfunction.
An alloimmune reaction.
1. Blood type A has A antigen and Anti B antibody. Incompatible with blood type B, AB.
2. Blood type B has B antigen and Anti A antibody. Incompatible with blood type A, AB
3. Blood type AB has A & B antigen and no antibody. Not incompatible with any blood type.
4. Blood type O has no antigen and has Anti A and Anti B antibody. Incompatible with blood type A, B, and AB
-There is a mutual relationship.
-Some microorganisms benefit and reside in the human body called normal flora.
-Relationship can be breached by injury (GI tract can release intenstinal bacteria into the blood causing sepsis. S. Aureus cause absess after cut)
-Opportunistic microgranisms- normal flora can infect those with immune deficiencies.
Can be stained and seen as gram positive or gram negative. They can produce a variety of toxic molecules that may kill cells, disrupt tissue, and protect against inflammation.
Exotoxins-proteins released during bacterial growth. Can damage cell membrane, activate second messengers, and inhibit protein synthesis.
Endotoxins- Released within the cell wall when bacteria is lysed. Antibiotics can't prevent the effects of these.
-Infection called mycosis. Can be superficial, deep, or opportunistic.
-Fungi that invade skin, hair, or nails is mild and known as dermatophytes. Ex: tineas (ringworm)
-Deep are life threatening and commonly opportunistic.
(FROM TABLE 9-7)
No tissue invasion, little inflammation.
-Fungus- Malassezia furfur causes tinea versicolor, seborrheic dermatitis, and dandruff. See red rash on body.
No tissue invasion with inflammatory response.
1. Trichophyton mentagrophytes cause cause tinea pedis (athlete's foot). See scaling, fissures, and itching.
2. Trichophyton rubrum cause tinea cruris (jock itch). See rash and itching
3. Microsporum canis causes tinea corporis (ringworm). See lesion, raised border, scaling.
4. Candida albicans causes cutaneous candidiasis. See lesions of skin, mucous membranes, thrush, vaginal inf.
1. sporothrix schenckii cause sporotrichosis. See ulcers or abscesses on skin and other organ systems.
Causes disease in healthy individuals.
1. Stachybotrys chartarum (black mold) causes black mold disease. See rash, headaches, nausea, and pain.
2. Coccidioides immitis causes coccidiodomycosis. See valley fever, flu like symptoms.
3. Histoplasma capsulatum causes histoplasmosis. See lung, flu like symptoms, disseminates to multiple organs, eye.
SYSTEMIC (OPPORTUNISTIC) FUNGI
1. Blastomyces dermatitidis causes blastomycosis. See flu like sx, chest pain.
2. Aspergillus fumigatus and flavus cause aspergillosis. See invastion to lungs and other organs.
3. Pneumocystis jiroveci causes pneumocystis pneumonia.
4. Cryptococcus neoformans causes cryptococcosis. See pneumonia like illness, skin lesions, disseminates to brain, meningitis
5. Candidia albicans causes systemic candidiasis. See sepsis, endocarditis, meningitis.
Viruses are intracellular parasites that do NOT have organelles.
-Replicate by taking over metabolic systems of host cell.
-May kill, take over, or be killed by immune system.
-Attaches to host cell via protein receptors.
-Releases info into host cytoplasm
*RNA virus enter host nucleus to produce mRNA(new viral material and provirus DNA (retrovirus, HIV)
* DNA virus enter host nucleus and may integrate into host DNA to make mRNA.
-Translation of virral specific mRNA results in viral proteins that self assemble.
-New virions are released from the cell for transmission of the viral infection to neighboring uninfected cells; budding.
-Viral DNA that is integrated into host cell; DNA is transmitted to daughter cell by mitosis. Viral genes then become a part of the genetic info of the cell.
Attenuated: weakened live virus (MMR, varicella, polio-oral)
Inactivated: Killed virus. (hepA, polio-injected, influenza)
1. Dead bacteria- not very effective in kids. EX pneumococcal
2. Conjugated- to carrier protein. incrases immunogenicity (Hib)
3. Toxoids- against bacterial toxins (DTap, DT)
Bacteria can become resistant to certain antibiotics, thus needing a new form of treatment.
1. inhibit synthesis of cell wall, 2. damage cytoplasmic membrane, 3. alter metabolism of nucleic acid, 4. inhibit protein synthesis, and 5. modify energy metabolism.
Anti viral- less successful because viruses use host enzymes.
-Caused by viral disease from HIV. This infects and depletes Th cells of the immune system, inc susceptibility to infection
-Incidence: World: 5 million/yr (Africa) US: 31,000/yr with 400,000 currently dx with AIDS.
-Effective antiviral therapy has made aids a chronic disease, not a death sentence
-Blood borne pathogens.
-HIV is a retrovirus which carries genetic info in the form of 2 copies of RNA (single stranded).
-Carries enzyme reverse transcriptase that creates a double stranded DNA version of itself from the RNA.
-Integrase (enzyme) inserts new DNA into the infected cells genetic material, where it remains dormant. Once activated, formation of new virions, lysis, and death of the cell (apoptosis) occur.
Theres depletionof CD4 cells.
-At time of dx may be serologically negative or positive and be asymptomatic.
-Antibody shows 4-7 weeks if infected via blood or 6-14 mo if sexually transmitted
-Window period-period between intro of virus to appearance of antibody.
-Aids DX is made with other clinical conditions.
-Early stage can last up to 10 yrs in untreated people, which viral load inc and CD4 decrease.
Progression to AIDS.
-Rapid decrease in CD4 and T cells where person becomes weak and acquire opportunistic infection.
-If CD4 <400/cubic mL, treatment is started.
-If CD4 < 200/cubic mL, cancer, lymphoma, fatal within 1 yr.
Highly active antiretroviral therapy.
-Use 3 or more drugs. 2 that target reverse transcriptase (fools DNA into incoporation into strands-halts it) and 1 that targets viral protease so cleaving of precursor proteins doesn't happen to make new viral protein.
-Not a cure, but slows progression.
-Taken rest of ones life.
-Very difficult to follow regimen. If stopped, virus becomes stronger and treatment is changed.
-Decrease risky behavior
-Use proper precautions when dealing with HIV pos people.
-Vaccines so far ineffective
-Fusion inhibitor. These interfere with fusion of HIV and CD4 cell
-Integrase inhibitor. These are undergoing trials on monkeys to slow disease progression.
-Entrance inhibitor. These use monoclonal antibodies to inhibit binding to co-receptors.
-There's a presence of passive maternal antibody. Limits the use of HIV testing in infants up to 15 mo of age.
-Impaired brain growth
-Encephalopathy occurs in late stage. Prognostic indicator of a poor outcome.
Structure of cell membrane. Contains lipids, cholesterol, carbohydrates, and proteins.
-Barrier to water and water-soluble substances.
-Organized in a bilayer of phospholipid molecules.
-Integral protein protrude through the membrane. Serve as receptors for water-soluble chemicals that can't easily penetrate.
-Peripheral protein do not protrude membrane. Function as enzymes or as controllers through cell membrane pores.
-Carrier proteins can transport substances that can't penetrate lipid bilayer opposite to their electrochemical gradient, called active transport.
-Serve as channels to allow diffusion from intra to extracellular fluid.
-Occur with protein (glycoprotein) or lipids (glycolipid).
-Attracts cells or acts as receptor (Insulin).
-Most integral proteins are glycoproteins.
1/10 of membrane are glycolipids.
-Have negative electrical charge that repels negative objects.
-Glycocalyx attaches to glycocalyx of other cells.
-Acts as receptor substances for binding hormones, thus activating intracellular enzymes.
-Some enter into immune reaction.
Passages of ions lead to electrical charge.
-Sodium (Na) is LOWER in cell
-Potassium (K) is HIGHER in cell
-Calcium (Ca) is LOWER in cell
- Chloride (Cl) is LOWER in cell
Ion channels pass these ions through cell membrane.
Carrier proteins can aid passage of these ions through other channel.
-Occurs DOWN a concentration gradient.
-No mediator or involves a "channel" or "carrier"
-No additional energy needed.
-Moves ions from higher to lower concentration.
-Lipid soluble molecules move more readily across the membrane. Rate depends on lipid solubility.
-Water soluble molecules move through channels or pores.
-Can be simple of facilitated.
Ungated- Selective on size and shape of molecule
Gated- Opens with voltage or chemical
EX: Voltage gated sodium channel allows only sodium. If intracellular is negative, and a positive ion comes, it opens.
EX: Chemical (ligand) is opened by binding of chemical substance with a protein. EX: Nicotinic ACh receptor channels.
-Uses specific carrier protein to help.
-Speed is limited by the Vmax of the carrier protein.
-Units are pmol/min/mg. Adding more carriers do not affect Vmax.
1. Concentration difference (Co-Ci). The more the concentration, the faster the rate. Net diffusion is proportion to the concentration difference.
2. Electrical potential (EMF). Depends on positive and negative charged ions that will eventually balance eachother. If positive intracell and negative extracell, the negative will move intracell to obtain equilibrium:
NERNST EQUATION: EMF= +/-61 log (c1/c2)
3. Pressure. Higher pressure results in increased energy available to cause net movement from high to low. EX blood capillary membrane.
-Occurs against a concentration gradient
-Involves a carrier
- Primary and secondary active transport.
Energy is derived directly from break down of ATP or other high energy phosphate compound. Direct use of energy molecules are pumped against a concentration at the expense of ATP. Includes sodium and potassium pumps, Calcium and hydrogen ions.
Sodium-potassium pump: Transports sodium out of cell membrane while pumping potassium in. Responsible for maintainng K/Na concentration.
-Energy derived from stored energy
-Indirectly uses energy from substances created by primary active transport.
1. Na-K ATPase
-Carrier protein located on plasma membrane of all cell.
-Plays important role in regulating osmotic balance by maintaining K/Na.
-Pump sends out 3 Na then brings in 2 K; as seen in ms and nerve signals.
-Present on the cell membrane and sarcoplasmic reticulum.
-Maintains a low cytosolic calcium concentration
-Intracellular calcium is low, but important for muscle contraction.
-calcium is pumped back into the sarcoplasmic reticulum of the cell.
PRIMARY ACTIVE TRANSPORT ENZYME- H ATPase.
-Found in parietal cells of gastric glands for HCL secretion
-Found in intercalated cells of rental tubules that control blood PH.
-Concentrates hydrogen ions up to 1-million fold.
Glycosides inhibit Na-K ATPase.
-Increase intracellular sodium
-Decrease sodium gradient
-Decrease Na/Ca counter transport
-increases intracellular Ca.
The charge difference across the membrane.
Passive diffusion of potassium and sodium can lead to negative membrane potential.
-If permeable to only K, it would flow either way. It would diffuse until electrial potential was at equilibrium (Ek). The same happens with sodium (Ena).
- At equilibrium, electromotive=chemical
nFv= RT ln (Ko/Ki)
-A regenerating depolarization of membrane potential that propogates along an excitable membrane.
-all or none events
-have constant amplitude. they do not summate. info coded by frequency, not amplitude.
-initiated by depolarization. can be induced in nerves and ms by extrinsic stim (percutaneous)
-involve change in permeability
-rely on voltage gated channels
-have constant conduction velocity. travel faster in myelinated fibers and in larger diameter fibers.
1. Information delivery to CNS. Block AP's in sensory nerves by local anesthetics because they are more effective in small diameter fibers.
2. Information encoding. The frequency of AP's encodes info; amplitude doesn't change.
3. Rapid transmission over distance.
-speed depends on fiber size and myelination
-non-nervous tissue AP's are initiators of cellular response
-secretion (epinephrine from chromaffin cells of medulla)
The ionic basis of the action potential
-channel type; voltage and receptor (ligand)
Properties of ion channel
-Selectivity (which ion can pass)
-gating (the process of open/close)
-voltage dependence (activation, deactivation, inactivation)
Action potentials are extracellularly recorded.
Synaptic transmission and graded membrane potential
-electrotonic conduction passive impulses
-excitatory and inhibitory (effect on post-synaptic cell). Summation (temporal and spatial)
*During upstroke: Sodium permeability increases, opening sodium channels to reach membrane potential (Ena)
*During downstroke: Sodium permeability decrease due to deactivation of sodium channels. Potassium permeability increases due to opening of potassium channels to reach membrane potential (Ek).
*After hyperpolarization, there is an increase in potassium conductance due to delayed closure of potassium channel, which is not always seen (see U at end of downstroke to resting potential)
Form walls of hollow organs (gut, blood vessel, airway, urogenital system)
Mononucleate cells with no striations.
*Multi-unit: Composed of discrete, separate smooth muscle fibers and operates independently. Innervated by a single nerve ending. Control exerted by nerve signals. Seen in eye and ms that exerts hair.
*Unitary: A mass of hundreds-thousands of fibers that contract together as a single unit. Fibers arranged in sheets/bundles, cell membranes adhere so force can be transmitted to the next. Seen in GI tract, bile ducts, ureters, uterus, and many blood vessels.
1. Can operate over large range of lengths.
2. Energy efficient
3. Can maintain force for long periods of time via latch state.
4. Can be myogenic (spontaneously active)
5. Has calcium action potential
6. Bell shaped length tension curve
7. Poorly developed sarcoplasmic reticulum
1. Endocrine: Epinephrine relaxation of the gut muscle and constriction of blood vessels. Cholecystokinin stimulated contraction of gall bladder. Angiotension 2, antidiuretic hormone, constriction of blood vessels.
2. Paracrine: Histamine stimulation of gastric contraction. Extracellular potassium, nitroc oxide, carbon dioxide, adenosine mediated relaxation of blood vessels.
3. Local nervous system: enteric system of gut
4. Autonomic nervous system: norepinephrine and acetylcholine constricts or contracts depending on sm. ms location.
1. Autonomic nerve fibers branch and form diffuse junctions with underlying smooth ms fiber.
2. Varicosities in terminal axons contain neurotransmitter
3. Neurotransmitter is secreted into matrix coating and diffuses to muscle cell.
4. Excitation is transmitted by calcium action potential or simple diffusion of calcium into fiber.
REGULATION IS MYOSIN (NOT ACTIN) BASED!!
*Contraction occurs by same actin-myosin interaction as striated ms
*Troponin complex is absent-calmodulin is similar.
*Enzyme myson light chain kinase (MLCK) phosphylates the light chain. Calcium sensitive b/c MLCK is active only in the presence of calmodulin.
-Initiated by calcium
-calcium binds to calmodulin
-ca-calmodulin-MLCK complex leads to phosphorylation of MLC (req 1 ATP)
-MLC is part of myosin head
-Phosphorylated myosin head binds to actin and power stroke occurs automatically
-A second ATP is required to relase myosin head from actin.
-Cross-bridge cycling requires MLCK and MLCP
-MLCP activity is regulated and can change calcium sensitivity.
Heart muscle is a syncytium of many heart muscle cells that are interconnected; if one becomes excited, the action potential spreads
Atrial and ventricular syncytiums work together as a pump
Similar to skeletal muscle with actin and myosin filaments making striations and lie next to eachother
Has low resistance intercalated disks (1/400 the resistance of cell membrane) that allow rapid diffusion of ions.
-Resting membrane potential is -85 to -95.
-Action potential is 105 mv, which then sends the resting membrane potential above 0 to postive 20 mv with each beat.
-There's a plateau where ventricular contraction occurs and lasts 0.2-0.3 secs.
-Longer than skeletal muscle.
The action potential occurs as plateau in ventricular contraction because fast sodium channels and slow calcium channels.
-Ca channels open slowly and remain open longer
-So, large quantity of sodium and calcium flow through, causing longer depolarization, causing a plateau.
-permeability to potassium decreases, which is caused by excess calcium influx; thus, this prevents early return of action potential to resting level.
phase 0- Fast sodium channels open then slow ca channels.
phase 1- Potassium channels open
phase 2- calcium channels open even more
phase 3- potassium channels open even more
phase 4- resting membrane potential
-The interval of time where a normal cardiac impulse cannot reexcite an already excited area of cardiac muscle.
-Ventricle refractory period is 0.25-.30 sec
-Atria refractory period is 0.15 sec
-Calcium release from sarcoplasmic reticulum by activating the calcium release channels (ryanodine)
-Calcium release also from t-tubules. (don't do this in skeletal ms.) which open voltage dependent calcium channels in the membrane of the t tubule.
-strength of contraction depends on calcium concentration
-Mucopolysaccharides bind calcium
-Cardiac events from beginning of one heartbeat to beginning of next
-Systole-Ventricular muscle stimulated by action potential and contracting.
-Diastole-Ventricular muscle reestablishing Na/K/Ca gradient; period of relaxation; heart fills with blood.
P wave= atrial wave
QRS= ventricular wave
T= ventricular repolarization
During the latter part of the ejection phase, blood leaves the ventricle even if pressure is higher in the aorta. This is because the total of energy of blood is pressure plus kinetic energy. So, the total energy of blood leaving the ventricle is greater than the aorta.
To compute EF, we need end diastolic and end systolic volume.
End diastolic volume=volume of blood during diastole (120ml)
End systolic volume= volume remaining in ventricle during systole (50 ml)
Ejection volume is ED-ES (70ml).
Ejection fraction is then EV/ED (58%)- use to figure cardiac output.
Cardiac output is computed by taking HR and multiplying it by stroke volume (or ejection volume)
-The intrinsic ability of the heart to adapt to increasing volumes of inflowing blood.
-The greater the heart muscle is stretched during filling, the greater the force of contraction and amount of blood pumped.
-"Within physiologic limits, the heart pumps all the blood that returns to it by the way of the veins."
-Extra blood stretches the cardiac muscle, thus causing actin and myosin to overlap more to optimal degree for increased force of contraction.
Sympathetic: stimulates inc in HR, causing fight or flight response. These integrate near the SA node and ventricles.
Parasympathetic: relaxes the heart, decreases HR, and decreases cardiac contractility through the vagi nerves. These integrage on the heart (mainly on atria) by one branch near SA node and other branch near AV node.
-Maximum sympathetic stimulation gives maximum cardiac output as right atrial pressure increases
-Normal sympathetic stimulation cardiac output is approximately 10 liters less than max
-No sympathetic stimulation is a few liters less/min than normal
-Parasympathetic stimulation is a few liters less than no sympathetic stim.
*change in CO relate to changes in HR and contractile strength
Potassium: Excess K causes heart to dilate and become flaccid; slows HR. Inc K can also block conduction of cardiac impulse through AV bundle. High extracellular K partially depolarizes the cell membrane, causing membrane potential to be less negative, so the membrane potential decreases, decreasing intensity of action potential, causing heart to become weak.
-Usually due to renal insufficiency, meds, etc. If K is 8-12 meqL (2-3x above norm), can cause arrythmia.
-Effects are opposite than K.
-Increase in Ca, inc cardiac contractility, causing spastic contractions.
-Decrease in Ca, causes flaccidity in the heart.
-Decrease in Ca has little clinical concern, unless caused by hypoparathyroidism, because calcium ion levels are regulated within a very narrow range.
Action Potential starts in the SA node, which acts as the pacemaker of the heart.-Resting potential of SA node is -55 to -60 mV, which is less than ventricular ms (-90mV)-Sinus fibers are leaky to Na and CA and positive charges of the entering of Na and Ca neutralize some of the intracellular negativity. Fast sodium channels cause rapid upstroke of AP b/c of rapid influx of Na in the fiber. Then a plateau occurs from the slower opening of slow na/ca channels. Then, K channels open to return membrane potential to resting level.
Starts in SA node: 0 sec
AV node: 0.03 seconds
AV bundle: 0.12 sec
Ventricular septum: 0.16 sec
SA node is main pacemaker with a rate of 70-80/min
But, other parts of the heart can exhibit intrinsic rhythmical excitation such as that iin the AV nodal fibers and Purkinje fibers
AV node fires at 40-60 per min
Purkinje fires at 15-40 per min
-Described as a pacemaker other than the sinus node.
-Has more rapid discharge than sinus node.
-Occurs when transmission from sinus node through AV node is blocked (AV block)
-During AV block, sinus node discharge doesn't get through, so next fast area of discharge is via purkinje system
-In this, there's a delay where ventricles fail to pump blood and the person faints. This is called Stokes-Adams syndrome.
-Parasympathetic (vagal) nerves innervate SA node and AV junctional fibers proximal to AV node and release acetylcholine. -Acetylcholine decreases the rate of rhythm of the sinus node and decreases excitability of the AV junctional fibers between atrail muscle and AV node, thus slowing transmission of impulse to ventricles.-There's an increase potassium permeability -Decreased transmission may temporarily stop heart, causing small area of purkinje system to develop a rate of its own, called ventricular escape.
-Increases rate of sinus node discharge
-Increases rate of conduction
-Increases force of contraction in atria and ventricle
-norepinephrine released at sympathetic nerve ending whic stimulate beta-1 adrenergic recepters, which mediate effects on heart rate.
-B blockers work here (-lol's) to block B1 adrenergic stimulation to decrease HR and force.
P- due to atrial depolarization
QRS- caused by potentials generated when the ventricles depolarize before contraction.
T wave- Period of repolarization of ventricles.
-Atrial repolarization not seen; hidden in QRS.
-Ventricles remain open until end of T wave.
Need RR interval
-If RR= 0.83 sec
-HR= (1 beat/0.83 sec) * (60 sec/1 min)
Cross out the 1, so, 60/0.83
HR is 72 bpm
Transport blood under high pressure to tissues. have strong vascular walls and blood flows at high velocity.
Blood circulates at a rate of 5 liters/min.
Exchange of fluid, nutrients, electrolytes, hormones, and other between blood and interstitial fluid.
The capillary walls are thin and have pores permeable to water and other small molecules.
Venules collect blood from capillaries and gradually coalesce into larger veins. Veins then serve as conduits for transport of blood from venules back to the heart. Pressure is low in veins and walls are thin.
Serves as reservoir to blood
Brings blood back to pulmonary circulation which is site of oxygen and carbon dioxide exchange.
Shows some of the components of circulation. Capillaries have the largest total area of circulation of 2500 cm; 1000 times that of the aorta.
Majority of blood volume is in the veins (64%)
Shows pressures in different parts of the circulatory system.
High pressure in arterial tree
Low pressures in venous side of circulation
Large pressure drop across arteriolar-capillary junction.
Brachial artery of arm is the closest to determining pressure b/c near area of aortic pressure.
-The rate of blood flow to each tissue of the body is almost always precisely controlled in relation to tissue need.
-The cardiac output is controlled mainly by the sum of all the local tissue flows.
-Arterial pressure regulation is generally independent of either local blood flow control or cardiac output control
-Streamlined: interior of blood vessel is smooth and of equal diameter along its length
-outermost layer moves slowest and center moves fastest
-When laminar flow occurs, the velocity of blood in the center of the vessel is greater than that toward the outer edge creating a parabolic profile.
-Laminar flow is silent.
-disorderly movement of blood in vessel when rate of blood flow becomes too great.
-Caused by high velocities, sharp turns, rough surfaces, rapid narrowing of vessels.
-Causes murmurs or bruits
-Important in diagnosing vessel stenosis, shunts, and cardiac valvular lesions.
-Increases wall stress (aneurysms, atherosclerosis)
-Flow (Q) through a blood vessel is determined by:
*The pressure difference between two ends of the vessel (P1-P2)
* Resistance (R) of the vessel
Vascular resistance changes with increased in HCT.
The higher the HCT, the thicker the blood viscosity, so the vascular resistance is increased.
-Leading cause of disease and death.
-Prevalence: 1:3 adults live with CVD (81.8 million)
-Modifiable risk factors include increased bp, cholesterol, cigarettes, diabetes, poor diet, lack of exercise, overweight and obesity.
-Genetic, neurohumoral, and inflammatory mechanisms
*Underlie tissue and cellular processes; endothelial injury, remodeling, stunning, reperfusion injury, and autoimmune disease.
Stretching of the veins; valves no longer function properly. Blood has pooled.
Distendended, tortuous, and palpable veins
Caused by trauma or gradual venous distention. Over a period of time, the pooled blood is depleted of necessary nutrients and oxygen; waste builds up.
Risk factors: standing for long periods, compression of abdominal veins (pregnancy), venous congestion
Treatment = Removal
-Inadequate venous return over a long period of time due to varicose veins or valvular incompetence.
-Pooled blood lead to inflammatory reaction, leading to ulceration.
-Any trauma or pressure can lower oxygen and nutrient supply, causing cell death adn necrosis, resulting in venous stasis ulcers.
-Obstruction of venous flow leading to increased venous pressure (usually in lower extremities)
-Caused by three factors (AKA triad of Virchow)
*1. Venous stasis (immobility, obesity, prolonged leg dependency, age, CHF)
*2. Venous endothelial damage (trauma, meds)
*3. Hypercoagulable states (inherited disorder, malignancy, pregnancy, oral contraceptives, hormone replacement, hyperchomocysteinemia, antiphospholipid syndrome)
DX made by obtaining D-dimer, ultrasound, xray, ct, mri, doppler flow.
-Local dilation or outpouching of a vessel wall or cardiac chamber.
-Laplace's law used to describe pressures on vessel walls that lead to aneurysm. In normal circumstances, for a given pressure, inc radius of the vessel requires inc wall thickness to stabilize wall tension.
-contributers: Arteriosclerosis, Atherosclerosis, Marfan syndrome or other collagen disorder, Infections, other.
-Hypertension is sustained elevation of 140/90 or higher.
-primary, secondary, complicated, and malignant HTN categories
-Essential or idiopathic hypertension
-Result of an interaction between genetics and environment that increase vascular tone and blood volume, thus causing increase in blood pressure.
-Affects 90-95% of individuals with HTN.
-Also get SNS contribution to increase blood pressure by promoting cardiac contractility and heart rate and by inducing arteriolar vasoconstriction...inc production of catecholamines (epinephrine, norepinephrine).
2. *insulin resistance, *dysfunction of the SNS, RAA, adducin, and natriuretic hormones, and *inflammation
3. *vasoconstricion and *renal salt/water retention
4. *Increased peripheral resistance *increase blood volume.
5. Sustained hypertension
****page 1151 figure 30-6
1. Increased SNS activity
2.*inc HR *inc insulin resistance *vascular remodeling *procoagulant effects.
3. *endothelial dysfunction *narrowing of vessels and vasospasm
Figure 30-7 page 1151
-male 55, female 70
-low intake of k, mg, ca
-Caused by systemic diseases that raises peripheral vascular resistance and cardiac output.
-Renal: renal failure, tumors, parenchymal disease
-Endocrine: Acromegaly, hypo/hyperthyroid, adrenal disorders
-Vascular: coarctation of the aorta, arteriosclerosis
-Chronic untreated hypertension damages walls of systemic blood vessels
-smooth muscle cells hypertrophy and hyperplasia with fibrosis of tunica intima and media causing vascular remodeling.
-Complications are left ventricular hypertrophy, CHF, angina pectoris, coronary artery disease, myocardial infarction, death.
-Rapidly progressive hypertension with diastolic pressure >140.
-Encephalopathy may occur b/c of high arterial pressure renders the cerebral arterioles incapable of regulating blood flow to the cerebral capillary beds.
-Death may occur if not corrected immediately due to cerebral edema.
-Depends on severity and type of hypertension
-Begins with lifestyle changes including restricting sodium, not smoking, inc potassium, decrease fat/calorie intake, exercise, and relax.
-Meds include Thiazide diuretics, but with those with kidney disease or other previous problems, treatment with ACE inhibitor , angiotensin receptor blocker, or aldosterone antagonist.
-Sometimes given combo of meds with thiazide diuretics and antihypertensives (beta blocers and ACE inhibitors)
-Chronic disease of arterial system
-Abnormal thickening and hardening of the vessel walls
-Smooth muscle cells and collagen fibers migrate to tunica intima.
-A form of arteriosclerosis
-Thickening and hardening caused by accumulation of lipid-laden macrophages in arterial wall.
-process occurring through out the body.
1. Injury of endothelial cells; become inflamed
2. cytokines released
3. Macrophages adhere to injured endothelium
4. macrophages release enzymes and toxic oxygen radicals creating oxidative stress, furthering injury to vessel wall and forming foam cells.
5. Growth factors released stimulating smooth muscle proliferation. Fatty streak formed from foam cells. Children may get this too.
6. Fibrous plaque made, thus obstructing blood flow
7. complicated plaques are ruptured plaques that form thrombus, resulting in ischemia and infarction
-Any vascular disorder that narrows or occludes the coronary arteries.
-Atherosclerosis is main cause.
*dyslipidemia *hypertension *cigarette *Diabetes mellitus *obesity/sedentary *defect in production of precurser endothelial cells.
*Markers of inflammation/thrombosis (CRP, fibrinogen, protein C, and plasminogen activator inhibitor) *hyperhomocysteinemia, *infection
-Develops if the supply of coronary blood can't meet the demand of the myocardium for oxygen and nutrients.
-Causes: tachycardia, exercise, hypertension (hypertrophy), and valvular disease; atherosclerotic plaques decrease blood flow to myocardium
-Ischemia happens within 10 sec of occlusion. Myocardial cells viable for 20 minutes, but after that, infarction occurs.
-have angina (stable, prinzmetal, silent, pectoris)
-Discomfort is transient lasting 3-5 mins
-have substernal chest discomfort, ranging from heaviness or pressure to moderately severe pain.
-May radiate to neck, lower jaw, left arm, and left shoulder.
-Build up of lactic acid or abnormal stretching of myocardial nerve fibers causes the pain.
-Chest pain attributable to transient ischemia of myocardium that occurs unpredictably and at rest.
-Pain caused by vasospasm; with or without atherosclerosis.
-Occurs when there is prolonged ischemia causing irreversible damage to the heart.
-May have non-ST elevation (non-STEMI) or ST elevation MI (STEMI).
-Non-stemi occurs when thrombus occludes, but then ends up breaking apart.
-If thrombus lodges permanently, infarction extends through myocardium all of the way into endocardium andepicardium, causing STEMI MI.
-ECG changes (see ST elevation)
*troponin: most specific. See in 2-4 hrs and remain elevated for 7-10 days.
*CK-MB: See in 2-4 hrs, peaks in 24 hrs. (may be elevated in those with other conditions)
*LDH: get hyperglycemia 72 hrs post MI.
-Also congestive cardiomyopathy
-See ventricular dilation and grossly impaired systolic function, leading to left heart failure.
-Most common causes are ischemic heart or valvular disease, renal failure, diabetes, but generally unknown.
-May have dyspnea or fatigue
-Either hypertrophic obstructive or hypertensive.
-Asymmetric septal hypertrophy
-Obstructive: commonly inherited; autosomal dominant. See thickening of septal wall, which may cause outflow obstruction to the left ventricle outflow tract.
-Hypertensive-Occurs b/c of inc resistance to ventricular ejection seen in HTN or valvular stenosis. have dyspnea, angina pectoris, fatigue, left heart failure.
-There's restrictive filling and reduced diastolic volume of either or both ventricles with normal or near normal systolic function and wall thickness.
-May occur idiopathically
-See Right heart failure with systemic venous congestion, dyspnea, and fatigue.
-General term used to describe several types of cardiac dysfunction that result in inadequate perfusion of tissues with blood borne nutrients.
-chronic condition that requires chronic disease management
-risk factors are diabetes, age, ischemic heart, obesity, and renal failure.
Left and right heart failure
-Defined as the inability of the right ventricle to provide adequate blood flow into pulmonary circulation at normal central venous pressure.
-Commonly caused by diffuse hypoxic pulmonary disease and left heart failure.
-Can result in left ventricular filling pressure back to pulmonary system.
-Systolic heart failure: an inability of the heart to generate an adequate cardiac output to perfuse vital tissues.
-diastolic is pulmonary congestion despite normal stroke volume and cardiac output.
-preload problem or failure to perfuse arteries
-causes increase venous back pressure
-Have SOB, leg swelling due to inability to pump blood back., intolerance to exercise
-Cardiogenesis begins at 3 weeks gestation
-heart arises from mesenchyme and begins development as an enlarged blood vessel with a large lumen and muscular wall.
-By 28 day, first fetal heart contraction occur
Oxygen enters via umbilical vein and arteries return blood back to placenta for nutrients and reoxygenation.
Foramen ovale allows blood to flow into right atrium.
Clamping of cord and first breath causes shift of gas exchange from placenta to lungs. There's an immediate increase in systemic vascular resistance and pulmonary vascular resistance decrease b/c of expansion.
-Ductus arteriosis and foramen ovale close due to increase left atrail pressure.
-Clamping causes veins and arteris to constrict
-Babies have thicker right ventricle than left b/c of pulmonary vascular resistance in fetal circulation.
-Heart points at a transverse angle.
-Hemodynamics; systemic vascular resistance rises, the LV becomes more developed and the systolic pressure rises steadily until it equals adult level at puberty
-HR is 100-180 b/c oxygen consumption.
-leading cause of death (except prematurity) in first year of life.
-Cause know in only 10% of defects.
-Factors may be:
*prenatal-rubella, diabetes, hypercalcemia
*environmental-drugs, alcohol, radiation, infection
*genetic-maternal pku, chromosomal aberrations.
2. Insufficient cardiac output relative to demand
3. cardiomyopathy most common cause
4. hypoxemia(cyanosis, eisenmenger syndrome)
-cardiovascular system failure to perfuse tissue adequately causing general impairment of cellular metabolism.
-A condition in which the circulatory system is unable to provide adequate circulation to the body tissues due to inadequate pumping by the heart, reduction in blood volume or blood pressure resulting in slowing of vital functions and possibly death
-Cardiogenic (caused by heart failure)
-Neurogenic/vasogenic (caused by alterations in smooth muscle tone)
-Hypovolemic (insufficient intravascular fluid)
-Traumatic (components of hypovolemic and septic)
-Patient complains of feeling sick, cold, hot, nauseated, dizzy, confused, afraid, thirsty, short of breath.
-BP, cardiac output and urinary output decreased
-Treatment: remove/correct underlying cause and supportive therapy.
-Impaired cellular metabolism is the final common pathway in ALL types of shock
-Perfusion is compromised, decreasing oxygen to cells.
-Cells shift from aerobic to anaerobic metabolism
*anaerobic uses ATP, losing electrochemical gradient; Na and Cl accumulate in the cell and K exits, reducing action potential amplitude. Water moves intracellularly, causing third spacing.
-Positive feedback loops further impair oxygen use by activating clotting cascade, dec circulatory vol, and lysosomal enzyme release. (procoagulative state)
-Impaired glucose use can be caused by either impaired glucose delivery or impaired glucose uptake by the cells.
-Cells shift to glycogenolysis, gluconeogenesis, and lipolysis to generate fuel to survive.
-Gluconeogenesis causes proteins to be used for fuel, thus are no longer available to maintain cellular structure, function, repair, and replication
*Get toxic levels of ammonia and uremia
*compensatory mechanism initiated: enables cardiac and skeletal muscles to use lactic acid as a fuel source for a limited time.
-Caused by myocardial ischemia, MI, CHF, myocardial or pericardial infection, dysrhythmia, and drug toxicity.
-As cardiac output decreases, compensatory adaptive responses are activated such as renin-angiotensin, neurohormonal, and sympathetic nervous systems that lead to fluid retention, systemic vasoconstriction, and tachycardia
-Catecholamines inc contractility and heart rate.
-Caused by inadequate perfusion to heart and end organs
-Subjective: chest pain, dyspnea, faintness, feeling of impending doom.
-Observed: tachycardia, tachypnea, hypotension, jugular venous distention, low cardiac output.
-May also see cyanosis, skin mottling; rapid, faint, or irregular pulses; low urine output, peripheral edema from end organ perfusion and pulmonary edema.
-Caused by loss of whole blood (hemorrhage), plasma (burns), or interstitial fluid (diaphoresis, diabetes mellitus/insipidus, emesis, or diuresis) in large amounts.
--Offset initially by compensatory mechanisms such as HR and SVR increase from catecholamine release by the adrenals, boosting cardiac output and tissue perfusion pressures. This improves blood pressure and perfusion to core organs.
-If mechanisms fail, impaired nutrient delivery and failing cellular metabolism.
-Also called vasogenic
-Widespread vasodilation from imbalance between parasympathetic and sympathetic stimulation.
-Causes persistant vasodilation and creates relative hypovolemia
*blood volume unchanged, but space containing blood increased, so SVR decreases
*pressure in vessels inadequate to drive nutrients across capillary membranes, imparing the cells.
-Caused by severe pain, stress, anesthesia, and depressant drugs. Trauma to spinal cord and medulla.
Anaphylactic shock patho
-Allergen causes extensive immune and inflammatory response
-Widespread hypersensitivity reaction leading to vasodilation, peripheral pooling, relative hypovolemia
-Extravascular effects include constriction of extravascular smooth muscle
*constriction often causes respiratory difficulty
-More severe due to other pathophysiologic effects.
-See anxiety, difficulty breathing, GI cramps, edema, hives, burning/itching sensation. May then get decrease in BP followed by impaired mentation.
-Treat with epinephrine to cause vasoconstriction
-Infectious processes initiate septic shock
-Six most common infectious sites:
1. lungs 2. bloodstream 3. IV cath 4. intraabdominal, 5. Urinary tact, 6. surgical wound.
-Bacteremia, endotoxins, and exotoxins initiate inflammatory process: releases complement, coagulation, kinin, and cellular immunity
-Inflammatory response causes widespread vasodilation.
Q: A person develops cardiogenic shock after an acute MI. The nurse understands this will produce:
1. inc acetylcholine
2. inc angiotensin II concentration
3. dec left ventricular afterload
4. dec norepinephrine
Answer is 2.
Everything else is opposite.
-Similar to neurogenic/anaphylactic shock.
-See low arterial pressure, low SVR from vasodilation, and alteration in oxygen extraction by all cells.
Q: A person with neurogenic shcok initially exhibits:
4. inc central venous pressure
Answer is 3.
Get hypotensive, bradycardic, and decreased CVP
-Progressive dysfunction of two or more organ systems due to an uncontrolled inflammatory response to a severe illness or injury.
-Shock and sepsis most common causes; but can happen from any injury or disease that initiates massive systemic inflammation: Trauma, major surgery, burns, acute pancreatitis, acute renal failure, ARDS.
-100 % mortality if 5 or more systems affected.
-The organ injury is directly associated with a specific insult, most often ischemia or impaired perfusion from an episode of shock or trauma, thermal injury, soft tissue necrosis, or invasive infection
-Decreased perfusion is local and generalized; usually can't be detected clinically
-Progressive organ dysfunction as a result from an excessive inflammatory reaction, after a latent period following the inital injury, iin organs distant from the site of the original injury.
-Second insult mild, but produces immense disproportionate response b/c of the previous priming of leukocytes
-Interaction of injured organs leads to a self perpetuating inflammation
1. maldistribution of blood flow
2. hypermetabolism with accompanying alterations in carbohydrate, fat, and lipid metabolism; initially a compensatory measure to meet energy demands.
3. myocardial depression; unclear
4. supply dependent oxygen consumption; imbalance in oxygen supply and demand from decreased oxygen delivery and inc oxygen needs
5. Reperfusion occurs when there is compounding of hypoxic damage to cells
*difficult to monitor b/c of lag time.
-See low grade fever, tachycardia, tachypnea, dyspnea, altered mental status, and general hyperdynamic and metabolic state in first 24 hrs.
-24-72 hrs see ARDS due to lung failure
-Days 7-10 : hypermetabolic and dynamic state intensifies; bacteremia with enteric organims is common; signs of hepatic, intestinal and renal failure develop
-Days 14-21: renal and liver failure; hematologic and myocardial failure, encephalopathy. Death then occurs after this if not resolved.
-Control initial iinflammatory process; fix absesses, debride necotic tissues, avoid catheters. Start antibiotics.
-Restore intravascular volume
-Aimed at providing oxygen and nutrition to support failing organs
Q: Endothelial cell dysfunction and mediator release in multiple organ system dysfunction syndrom produces:
1. a net procoagulant state
3. a reduction in oxygen free radicals
4. decreased proteases
Answer is 1.
get vasodilation, inc in free radicals due to neutrophils, and increased proteases.
-poor feeding and sucking: failure to thrive
-dyspnea, tachypnea, diaphoresis, retractions, grunting, nasal flaring
-Wheezing, coughing, rales are rare
-Skin changes; mottling or pallor
1. Excrete metabolic waste products urea, creatinine, bilirubin, hydyrogen.
2. Excrete foreign chemicals: drugs, toxins, pesticides, food additives
3. Secretion, metabolism, and excretion of hormones (renal erythropoetic factor, 1,25 dihydroxycholecalciferol-Vit D, renin)
4. Regulation of acid-base balance
5. Gluconeogenesis: glucose synthesis from amino acids
6. Control of arterial pressure
7. Regulation of water and electrolyte excretion
-Urea from protein metabolism
-Uric acid from nucleic acid met.
-Creatinine from ms. met
-Bilirubin from hgb met.
-Metabolites of hormones
Anatomy of kidney:
1. The medial side of a kidney contains an indented region called the hilum through which pass the renal artery, and vein, lymphatics, nerve supply, and ureter.
2. The outer border has open ended pouches called major calyces that divide into minor calyces, which collect urine from tubules of each papilla. The walls of calyces, pelvis, and ureter contain contractile elements that propel the urine toward the bladder.
Thick and thin loop of henle
-Thin descending is highly permeable to water and moderately permeable to most solutes (urea,NA)
-Thick segment has high metabolic activity and actively reabsorbs about 25 % of NA, Cl, & K. Ca, bicarb, and mg are also reabsorbed.
-Thick also mediates Na reabsorption adn H secretion. Virtually impermeable to water. Loop diuretics site of action is here (furosemide, ethacrynic acid, and bumetanide by inhibing co-transporter.
-Functionally similar to the thick ascending loop
-NOT permeable to water (diluting segment)
-Active reabsorption of Na, Cl, K, Mg
-Contains macula densa which is a group of closely packed epithelial cells that is part of the juxtaglomerular complex and provides feedback control of GFR and blood flow in same nephron.
-5% of the filtered load of sodium chloride is reabsorbed in early distal tubule. Thiazide diuretics inhibit the sodium-chloride transporter here that moves sodium from tubular lumen into the cell and the Na/K ATapase pump transports sodium out of the cell across basolateral membrane. Not permeable to water and not very permeable to urea.
-In the late distal tubule, permeability of water depends on ADH. High ADH, water is reabs (opp for low). Not very permeable to urea. Reabsorbs sodium ions and secrete hydrogen ions by hydrogen-ATPase mech.
-Medullary collecting duct. The permeability of water is controlled by ADH. With high ADH, water reabs, thus reducing urine volume and concentrating most of the solutes in the urine.
-Permeable to urea with special urea transporters that facilitate urea diffusion across the luminal and basolateral membranes.
-Secrete hydrogen ions across large concentration gradient.
1. Glomerular filtration 2. Reabsorption of substances from renal tubules into blood 3. Secretion of substances from the blood into renal tubules
* Not selective unless bound to plasma proteins (plasma Ca, Plasma fatty acids). Glomerular filtration is 20% of renal plasma flow. Neg charged large molecules filter less easily than pos of same size, but larger are less easily filtered in general.
-Early detection of renal disease in at-risk patients:
*Hypertension: hypertensive renal disease
*Diabetes: diabetic nephropathy
*pregnancy: gestation proteinuric hypertension (pre-eclampsa)
*Annual "check up": renal disease can be silent
-Assessment and monitoring of known renal disease
-Defined as urine excretion of >30, but <150 mg albumin/day
-Causes: early diabetes, htn, glomerular hyperfiltration
-Prognostic value: diabetic patients with microalbuminura are 10-20 fold more likely to develop persistent proteinuria.
GFR=125ml/min=180L/day; so, the entire plasma can be filtered and processed 60x/day. High GFR allows the kidneys to precisely and rapidly control the volume and composition of body fluids.
-Glomerular filtrate composition is same as plasma, except large proteins.
-Filtration fraction: GFR/Renal plasma flow; usually 0.2 b/c of 20% of plasma filtered.
Water (L/day): Filtration-180, Reabs-179, Exc-1
Sodium (mmol/day): Filt-25,560, reabs-25,410, exc-150
Glucose (gm/day): Filt-180, reabs-180, exc-0
Creatinine (gm/day): filt-1.8, reabs-0, exc- 1.8
GFR is determined by the 1. sum of hydrostatic and colloid osmotic forces across glomerular membrane, which gives net filtration pressure, and 2. the glomerular capillary filtration coefficient (K1).
GFR=K1 * net filtration pressure
Net filtration pressure is sum of hydrostatic and colloid osmotic forces. Forces include hydrostatic pressure inside glomerular capillaries, hydrostatic pressure in bowman's capsule, the colloid osmotic pressure of the glomerular capillary plasma proteins, and colloid osmotic pressure of the proteins in bowmans capsule.
Determination of glomerular filtration rate (GFR)
-Normal renal blood flow is about 1100ml/min or about 22% of cardiac output.
-High blood flow needed for High GFR
-Oxygen and nutrients delivered to kidneys normally greatly exceed their metabolic needs
-A large fraction of renal oxygen consumption is related to renal tubular sodium reabsorption.
1. SNS/catecholamines: Activation decreases GFR. Can constrict renal arterioles and decrease renal blood flow and GFR. Renal sympathetic nerves seem to be most important in reducing GFR during severe, acute disturbances lasting for a few minutes to a few hours, such as those elicited by the defense reaction, brain ischemia, or severe hemorrhage.
2. Angiotensin 2 preferentially constrict efferent arterioles in most physiologic conditions. It is locally produced autacoid because it is formed in the kidneys and systemic circulation. Seen during low sodium diet or dec renal perfusion r/t stenosis.
Tend to increase GFR. Cause vasodilation and increased renal blood flow and GFR. Usually important ONLY when there are other disturbances that are already tending to lower GFR.
Under stressful conditions, such as volume depletion or after surgery, the administration of NSAID's, such as aspirin, that inhibit prostaglandin synthesis may cause significant reduction in GFR.
This is an autocoid that decreases renal vascular resistance and is released by the vascular endothelium throughout the body.
Important for maintaining vasodilation of the kidneys that protects against excessive vasoconstriction. Allows kidney to excrete normal amounts of sodium and water.
In some hypertensive patients or with atherosclerosis, damage of vascular endothelium and impaired nitric oxide production may contribute to increased renal vasoconstriction and elevated BP. They also have dec GFR in volume depeletion.
SNS (dec GFR/dec RBF)
Catecholamines (dec GFR/dec RBF)
Angiotensin 2 (no change GFR/dec RBF)
EDRF (inc GFR/inc RBF)
Endothelin (dec GFR/dec RBF)
Prostaglandins (inc GFR/inc RBF)
Autoregulation of GFR and RBF by:
1.Myogenic mechanism-allows the ability of individual blood vessels to resist stretching during increased arterial pressure.
2. Macula Densa feedback (tubuloglomerular)-Mechanism that links changes in sodium chloride concentration at the macula densa with the control of renal arteriolar resistance. Ensures a constant delivery of sodium chloride to the distal tubule and helps prevent spurious fluctuations in renal excretion
3. Angiotensin 2-Constriction helps prevent serious reductions in glomerular hydrostatic pressure and GFR when renal perfusion pressure falls below normal.
1. Fever, pyrogens; inc GFR
2. Glucocorticoids; inc GFR
3. Aging; dec GFR 10%/decade after 40 yrs of age
4. Hypoglycemia; inc GFR (diabetes mellitus)
5. Dietary protein: high proten inc GFR/low protein decrease GFR
Net reabsorption of Na from the tubular lumen into blood occurs:
1. Na diffuses across luminal membrane into cell down electrochemical gradient by Na/K ATPase pump on basolateral side of membrane
2. Na transported across basolateral membraneagainst electrochemcial gradient by Na/K ATPase pump
3. Na, Water, and other substances are reabsorbed from interstitial fluid into peritubular capillaries by ultrafiltration
Some substances have max rate of tubular transport due to saturation of carriers, limited ATP, etc
-Transport max: once this is reached for all nephrons, further increases in tubular load are not reabsorbed and are excreted
-Threshold is the tubular load at which transport max is exceeded in some nephrons. This is not exactly the same as transport max of whole kidney b/c some nephrons have lower transport max than others
-Ex are glucose, amino acids, phosphate, sulfate
This shows mechanisms by which water, chloride, and urea reabsoprtion are coupled with sodium reabsorption.
The active reabsorption of sodium is closely coupled to the passive reabsorption of chloride by way of an electrical potential and a chloride concentration gradient. Chloride ions reabsorption involves co-transport of chloride with sodium across the luminal membrane. Urea is less reabsorbed than chloride. As water is reabsorbed, urea concentration in tubular lumen increases, thus creating concentration gradient favoring reabsorption of urea. Half is filtered, rest excreted.
Concentrations of solutes in different parts of the tubule depend on relative reabsorption of the solutes compared to water.
-If water is reabsorbed to a greater extent than the solute, the solute will become more concentrated in the tubule (ex: creatinine)
-If water reabsorbed to lesser extent than solute, the solute will become less concentrated in the tubule )ex: glucose, amino acids)
1. Glomerulotubular balance
2. Peritubular physical forces
4. Sympathetic nervous system
5. Arterial pressure
6. Osmotic factors
-The ability of the tubules to increase reabsorption rate in response to increased tubular load.
-Helps to prevent overloading of the distal tubular segments when GFR increases
Hydrostatic and colloid osmotic forces govern the rate of reabsorption across the peritubular capillaries, just as they control filtration in the glomerular capillaries.
Changes in peritubular capillary reabsorption can in turn influence the hydrostatic and colloid osmotic pressures of the renal interstitium and, ultimately, reabsorption of water and solutes from the renal tubules.
1. Aldosterone stimulates Na reabsorption and K secretion. The most important stimuli for aldosterone are inc extracellular K and angiotensin 2 levels. Lack of aldosterone (addisons dis) there's loss of Na and inc K. Or excess with adrenal tumors (conn's syndrome) inc Na and dec potassium due to excessive K secretion by kidneys.
2. Angiotensin 2: Increased helps to return blood pressure and extra cellular volume toward normal by increasing sodium and water reabsorption from the renal tubules through: stimulating aldosterone, constrict efferent arterioles, and directly stimulate Na reabsorption in all tubules.
-Antidiuretic hormone (ADH): Increases water reabsorption, especially in dehydration, alcohol inhibits secretion, causing inc urination. Helps the body to conserve water.
-Natriuretic hormones (ANF): Decreases sodium and water reabsorption. Secreted by cardiac atria when distended. Directly inhibits the reabsorption of sodium and water by renal tubules; esp collecting ducts. Inhibits renin secretion, thus angiotensin 2 formation, which reduces tubular reabsorption. Increases urinary excretion. Elevated in CHF
-Parathyroid: Inc Ca reabsorption
-Water reabsorbed ONLY by osmosis.
-Changes in peritubular capillary physical forces influence tubular reabsoprtion by changing the physical forces in the renal interstitium surrounding the tubules.
-Increasing the amount of unreabsorbed solutes in the tubules decrease water reabsorption.
1. Conn's syndrome: primary aldosterone excess
2. Glucocorticoid remediable aldosteronism (GRA): excess aldosterone secretion due to abnormal control of aldosterone synthase by ACTH (genetic)
3. Renin secreting tumor: excess angiotensin 2 formation
4. Inappropriate ADH syndrome: excess ADH
5. Liddle's syndrome: excess activity of amiloride sensitive Na channel (genetic)
1. Diabetes Insipidus: Decreased water reabsorption, hypernatremia. Nephrogenic, Lack of ADH
2. Addison's disease: Decreased Na reabsorption and decreased K secretion; lack of aldosterone
3. Bartter's Syndrome: Dec Na, Ca, HCO3 reabsorption, hypotension; decreased activity of Na-K-2 Cl transporter in loop of henle.
4. Gitleman's Syndrome: Decreased NaCl reabsorption, hypotension; decreased activity of NaCl co-transporter in distal tubule (genetic)
1. Fanconi Syndrome: generalized decrease in reabsorption often in proximal tubules. Caused by genetics, heavy metal damage, drugs (tetracyclines), multiple myeloma, tubular necrosis (ischemia)
2. Renal tubular acidosis: Decreased hydrogen secretion, increased HCO3 excretion, acidosis. Caused by genetics, renal injury, etc
1. Plasma concentration of waste products (BUN, creatinine)
2. Urine specific gravity, urine concentrating ability
3. UA strip (protein, glucose, etc)
5. Albumin excretion (microalbuminuria)
6. Imaging (MRI, PET, arteriogram, pyelography, us)
7. Clearance method (24 hr creatining clearance)
-Describes the rate at which substances are removed (cleared) from the plasma
-Renal clearance of a substance is the volume of plasma COMPLETELY cleared of a substance per min by the kidneys.
Renal Clearance (Cs) of a substance is the volume of plasma COMPLETELY cleared of a substance per min.
Us*V is the urine excretion rate
Us is urine concentration of substance
V is urine flow rate
Ps is plasma concentration of a substance
5. Inulin=125 (not excreted/not reabs)
7. PAH=600 (completely exc)
*For a substance that is freely filtered, but not reabsorbed or secreted (inulin, I-iothalamate, creatinine), renal clearance is equal to GFR
*Amount filtered=amount excreted
*Inulin is freely filtered by glomerular capillaries, but not reabsorbed by renal tubules.
If muscle mass remains constant, creatinine excretion should remain constant. GFR is DIRECTLY related to the reciprocal of creatinine concentration. Serum creatinine can only be used in patients with STABLE kidney function. GFR is decreased in ARF, but serum level won't show. Creatinine may be inc after a large protein meal (meat, etc).
Creatinie is a by product of muscle metabolism and is cleared from body fluids almost entirely by glomerular filtration. It may not be a perfect marker of GFR b/c a small amt is secreted by tubules, so amt exc may slightly exceed amt filtered.
ADH+thirst= ADH thirst osmoreceptor system
*increased extracellular osmolarity (NaCl) stimulates ADH release, which increases water reabsorption, and stimulates thirst
When there is excess water in the body and body fluid osmolarity is reduced, the kidney can excrete rine with an osmolarity as low as 50 mOsm/L, which is 1/6 of normal extracellular fluid. Also, if there is a deficity of water and extracellular fluid, osmolarity is high, the kidney can excrete urine with concentration of 1200-1400mOsm/L
Max conc= 1200-1400mOsm/L (specific gravity~1.030)
Minimal conc= 50-70 mOsm/L (specific gravity~1.003)
-Continue electrolyte reabsorption
-Decrease water reabsorption
Mechanism: Decreased ADH release and reduced water permeability in distal and collecting tubules.
Tubular fluid remains isoosmotic in the proximal tubule; then diluted in the ascending loop of Henle; then fluid in distal and collecting tubules is further diluted in the absence of ADH.
-Continue electrolyte reabsorption
-Increase water reabsorption
-mechanism: Increased ADH release increases water permeability in distal and collecting tubules. High osmolarity of renal medulla provides osmotic gradient necessary for water reabsorption to occur in the presence of high levels of ADH. Countercurrent flow of tubular fluid depends on the special anatomical arrangement of the loops of henle and the vasa recta, the specialized peritubular capillaries of the renal medulla.
1. Proximal tubule: 65% reabsorption, isosmotic
2. Desc. Loop: 15% reabsorption, inc osmolarity
3. Asc loop: 0% reabs, dec osmolarity
4. Early distal: 0% reabs, dec osmolarity
5. Late distal/coll tubule: ADH dependent water reabsorption and tubular osmolarity
6. Medullary coll duct: ADH dependent water reabsorption and tubular osmolarity
-Failure to produce ADH: "central" diabetes insipidus
-Failure to respond to ADH: "nephrogenic" diabetes insipidus
*impaired loop NaCl reabs (loop diuretics/furosemide)
*Drug induced renal damage: lithium, analgesic, tetracycline
*Malnutrition (dec urea concentration)
*Kidney disease: pyelonephritis, hydronephrosis, chronic renal failure.
1. Increased osmolarity: Inc in plasma Na concentration; causes osmoreceptor cells in the anterior hypothalamus to shrink, thus relaying signals to posterior pituitary to stimulate release of ADH.
2. Decrease blood volume and pressure (cardiopulmonary reflexes and arterial baroreceptors). The arterial baroreceptor reflexes and cardiopulmonary reflexes respond relaying signals to hypothalamic nuclei that control ADH synthesis and secretion.
3. Other includes input from cerebral cortex (fear), nausea, angio 2, nicotine, morphine.
1. Decreased osmolarity
2. Inc blood volume
3. INc blood pressure
4. Other: alcohol, cloniding, haloperidol (antipsychotic, Tourette's)
1. Increased osmolarity
2. Decreased blood volume (cardiopulm reflexes)
3. Decreased blood pressure (arterial baroreceptor)
4. Increased angiotensin 2
5. Other: dryness of mouth
-A blockage of urine flow within the urinary tract.
-Can be caused by an anatomic or functional defect like obstructive uropathy
-Severity is based on location, completeness, involvement of one or both upper urinary tracts, duration, and cause.
-Hydroureter: dilation of the ureter
-Hydronephrosis: dilating of renal pelvis and calyces
-Ureterohydronephrosis: dilation of both ureter and pelvicaliceal system
-Tubulointerstitial fibrosis: the deposition of excessive amounts of extracellular matrix (collagen/protein)
-Apoptosis; imbalance of factors provoked by obstruction leads to excess cell destruction
-Compensatory hypertrophy and hyperfunction: compensatory response is result of obligatory growth that occurs under influence of somatomedins, and compensatory growth occurs under influence of hormones.
-Postobstructive diuresis: physiologic response with restoration of fluid and electrolyte imbalance caused by obstructive uropathy; brief.
1. Crystal growth-inhibiting substances; includes Tamm-Horsfall protein, potassium citrate, pyrophosphate and magnesium are capable of crystal growth inhibition, thus reducing risk of precipitation and preventing stone.
2. Particle retention-seen at paipillary collecting ducts
3. Matrix-organic material that is formed in presence of urea splitting pathogens; high in stones associated with infection
1. Supersaturation of one or more salts; presence of a salt in higher concentration than the volume able to dissolve the salt
2. Precipitation of a salt from liquid to solid state; temp and pH. pH alkaline inc risk of calcium phosphate stone and acidic inc uric acid stone.
3. Growth into a stone via crystallization or aggregation. Crystallization is the process by which crystals grow from a small nucleus to larger stones in supersaturated urine.
4. Presence or absence of stone inhibitors
3. Change in urine pH
4. Spinal cord injury
6. Inc calcium or oxalate rick food
7. Metabolic factors
8. Renal tubular acidosis and inc uric acid
** (main)Severe pain; intensity can fluctuate. Usually originating in the flank and radiates to the groin, usually indicative obstruction of renal pelvis or proximal ureter. Pain causes nausea and vomiting.
**Gross or microscopic hematuria may be present
General term for bladder dysfunction caused by neurologic disorders. Lesions that develop in upper motor neurons of the brain and spinal cord result in dyssynergia (loss of coordinated neuroms contraction) and overactive bladder function. Lesion in sacral area of spinal cord or peripheral nerves result in underactive, hypotonic, or atonic bladder
**includes detrusor hyperreflexia, detrusor hyporeflexia with vescicosphincter dyssynergia, and detrusor areflexia.
**Known as an uninhibited or reflex bladder. This is an upper motor neuron disorder in which bladder empties automatically when it's full and external sphincter functions normally. Neuro disorder above pontine micturition center
**Since pontine micturation center is intact, there is coordination between contractions and relaxation of sphincter.
**Causes include stroke, TBI, dementia, and brain tumor. **SX: urine leakage and incontinence.
*Neurologic lesions that occur below pontine micturition center, but above sacral micturition center (C2-S1) are also upper motor neuron lesions. Loss of pointine coordination of detrusor muscle contraction and sphincter relaxation, so both bladder and sphincter contract at same time, causing function obstruction of bladder outlet.
See in Spinal injury, MS, Guillain-Barre, intervertebral disk problem.
SX: frequency, urgency, and urge incontinence with inc risk for urethral turbulence and UTI
Lesions that involve the sacral micturition center (below S1) or peripheral nerve lesions result in detrusor areflexia, a lower motor neuron disorder. There is acontractile detrusor or atonic bladder with retention of urine and distention. If sensory innervation intact, full bladder is sensed, but detrusor may not contract.
SX: stress and overflow incontinence
Causes: Myelodysplasia, mS, tabes dorsalis, and peripheral polyneuropathies.
Classified by location or complicating factors:
-cystitis (bladder inflammation)
-pyelonephritis (inflammation of upper urinary)
-Uncomplicated (occur in normal function urinary system)
-Complicated (occur with defects in urinary system or with other health problems.)
Most common pathogens are E.Coli, S. saprophyticus, Enterobacter. Virulence is a pathogen's ability to evade or overwhelm the host defense and cause disease. Sterility is maintained even with bacterial presence.
Urinary infection that involves inflammation of the bladder. Most common site of UTI.
-Individuals are usually asymptomatic, but then see frequency, urgency, dysuria (painful urination), and subrapubic/low back pain. Hematuria, cloudy and foul smelling urine and flank pain are more serious symptoms.
-Treatment: antibiotics (usu 3-7 days), inc fluids, avoid bladder irritants, and urinary analgesics.
-Acute infection of the ureter, renal pelvis, and/or renal parenchyma
-Contributing factors include cystitis, urinary tract obstruction with reflux infection (most common), women, pregnancy, neurogenic bladder, trauma, catheter/scopes.
-Clinical manifestations: flank pain, fever, chills, costovertebral tenderness, purulent urine, frequency, dysuria
-Nephrotic sediment contains massive amount of protein and lipids. May or may not have hematuria.
-Nephritic sediment has presence of hematuria with red cell casts, white cell casts, and varying degrees of protein.
-May have sudden onsent of HTN, edema, inc BUN
-Decreased GFR, inc plasma creatinine, inc urea, and dec creatinine clearance
-Damage causes dec glomerular membrane surface area, glomerular capillary blood flow, blood hydrostatic pressure
An inflammation of the glomerulus caused by numerous things such as; infection, immunologic abnormalities (most common), ischemia, free radicals, drugs, toxins, vascular disorders, and systemic disease including diabetes mellitus and lupus.
**Most common cause of chronic kidney disease and end stage renal failure.
-Have decreased GFR; decreased glomerular perfusion r/t inflammation, glomerular sclerosis, and thickening of the glomerular basement membrane (but inc permeability to proteins)
-Hematuria; see smoky, brown tinged urine. red cell casts
-Proteinuria: low serum albumin and edema
-Eventual oliguria; urine output is <30ml/hr or <400ml/day
No specific treatment, but is focused on underlying disease. Giving antibiotics for infection, vasodilators for HTN, or corticosteroids to suppress inflammation.
Children who get this recover without significant loss of renal function
-Urine excretion of 3.5 mg or more of protein in urine per day
-Protein excretion is due to glomerular injury
-See; hypoalbuminemia, edema, hyperlipidemia, and lipiduria.
2. Genetic defects that alter glomerular membrane
3. Systemic disease (diabetes, SLE)
4. Drug/toxin injury
5. Infection (esp chronic/recurrent)
Begins 7-10 days after strep infection of skin or throat.
-Formation of antigen/antibody complexes in circulation which deposit into glomerulus.
-Antibodies produced against strep cross-react wit glomerular endothelial cells
-Activation of complement
-Recruitment/activation of immune cells and mediators
-dec vitamin D
Refers to significant loss of renal function. When <10% of renal functioin remains, this is termed end stage renal failure
Renal insufficiency, renal failure, uremia, and azotemia are associated with DECREASED renal function, but not specifically kidney function. Used synonymously, but have differences
*Acute: sudden and rapid progressive within hours. Reversible, abrupt reduction in renal function
*chroic: slow progressing to end stage renal failure over months or years
Most common cause of ARF. Caused by impaired renal blood flow. GFR declines due to decrease in filtration pressure (results in oliguria). Ischemia leads to hypoxic injury and acute tubular necrosis (ATN).
MI, heart failure, and other CV disorders contribute to risk for impaired kidney blood flow.
Hypovolemia, peripheral vasodilation, obstruction, or severe vasoconstriction can impair renal blood flow. Causes also include hemorrhage, burns, water loss (vomit, diarrhea, diabetes mellitus, diuretics), septic shock, PE
Damage to the renal parenchyma.
May result form acute tubular necrosis (ATN/most common), nephrotoxic ATN, acute glomerulonephritis, vascular disease (malignant htn, DIC, and renal vasculitis), allograft rejection, or interstitial disease (drug allergy, infection, tumor growth), cortical necrosis, toxic injury (antibiotics/nephrotoxic)
ATN comes from unrecognized or untreated pre renal failure. OB complications and sepsis can also cause.
Occurs with urinary tract obstructions that affect the kidneys bilaterally and increase the intraluminal pressure upstream (thus fall in GFR)
Causes include prostatic hypertrophy, bladder outlet obstruction, bilateral ureteral obstruction.
See flank pain followed by polyuria
Clinical manifestations of ARF
2. Inc BUN and creatinine
3. Metabolic acidosis
5. Hypertension (volume overload)
The progressive, irreversible loss of renal function associated with systemic diseases such as HTN, diabetes mellitus, chronic glomerulonephritis, chronic pyelonephritis, obstructive uropathies, vascular disease congenital anomalies, collagen disease, and nephrotoxic agents. Kidney damage that has GFR <60ml/min/1.73 m2 for 3 months or more.
1. reduced renal reserve (GFR 35-50% of normal rate: 60-89ml/hr)
2. renal insufficiency (GFR 20-35%: 30-59ml/min)
3. renal failure (GFR 20-25%: 15-29ml/min)
4. end stage renal disease (GFR <20% of normal rate: <15ml/min)
1. Creatinine and urea clearance: Creatinine is constantly excreted, so plasma levels continue to increase as GFR decrease; creatining can serve as an index of glomerular function. Urea has similar pattern, but it's filtered and reabsorbed so not a good index of GFR
*Sodium load delivered to nephrons exceed normal, so excretion must increase; thus less is reabsorbed. Obligatory loss occurs, leading to sodium deficits and volume depletion. As GFR is reduced, ability to concentrate and dilute urine diminishes.
*The regulation of water balance and osmolality is normally achieved by urinary concentration mediated by ADH.
*Tubular secretion of K increases until oliguria develops. Use of potassium-sparing diuretics may precipitate elevated serum potassium levels. As disease progresses, totoal body potassium levels can rise to life-threateing levels and dialysis is required.
*Secretion is mediated by aldosterone and sodium-potassium ATPase
Males often experience a reduction in testosterone and may be impotent. Oligospermia and germinal cell dysplasia can result in infertility. Females have reduced estrogen, amenorrhea, and difficulty carrying to term. Decrease in libido in both sexes.
Insulin resistance is common. The ability of the kidney to degrade isulin is reduced and half life of insulin is prolonged. Alterations in thyroid hormone may occur.
Water moves through the lipid bilayer cell membrane through aquaporins
Water passes easily and quickly among body compartments, to maintain osmotic equilibrium, in response to changes in solute concentration.
Net filtration=forces favoring filtration - forces opposing filtration
**forces favoring filtration, or movement of water out of the capillary and into the interstitial space, include the capillary hydrostatic pressure and interstitial oncotic pressure
**forces opposing filtration are the plasma oncotic pressure and the interstiital hydrostatic pressure. Normally a small percent of plasma protein cross capillary membrane, so major forces for filtration are within the capillary.
Changes in TBW are accompanied by proportional changes in electrolytes and water
Water/solute concentration equal to 0.9% NaCl
No shrinkage or swelling of cells.
Loss of isotonic fluids include hemorrhage, wound drainage, diaphoresis, intestinal loss, decreased fluid intake. Excess is from inc IVF or oversecertion of aldosterone.
Changes in TBW that result in ECF concentration of >0.9% NS
Cells shrink from water loss or solute gain.
Water tries to make it where there is equilibrium in cell and out of cell. If inc solute out, water will leave cell, thus shrinkage
Imbalance in TBW that results in ECF <0.9% ns
Cells swell from water overload.
Consumption of too much water or intravenous fluids.
TBW>ICF&ECF then from ECF>intersistitial fluid and intravascular fluid
*women TBW 50% (wt in Kg and expressed in liters)
*men TBW 60%
*Infants have greater percentage (70%)
*Obese lower percentage
Excessive accumulation of fluid within interstitial places.
Get loss of plasma protein then decreased plasma osmotic pressure. Results from kidney disease, drainage from open wound, hemorrhage, burn, and liver cirrhosis. Inflammation and immune response associated with inc capillary permeability. Burns, crushing injuries, and allx reaction allow protein to escape and produce edema. Infection and tumor can block lymp; surgical removal of lymph can cause protein and fluid to accumulate causing lymphedema.
Normal Na=135-145mEq/L. Hyponatremia is <135
Seen in 30% of nursing homes that req hospitalization. Water intake exceeds output. Impaired renal diluting capacity (dec GFR). Persistent ADH secretion despite depressed serum osmolality.
Urinary loss of sodium at a rate that exceeds intake (diuretics, CHF, Gi loss)
Determines plasma osmolality
Osmotic pressure gradient > water entering brain cell and cerebral edema is acute
*disorientation, agitation, hyporeflexia
*Rapid Na reduction; coma, seizure
*Mortality rate 5-50%; depends on cause and management
Caused by inadequate free water intake, inappropriate amount of hypertonic saline, oversecretion of aldosterone, cushing syndrome (inc aldosterone), diabetes insipidus (dec ADH), diarrhea
-Water in extracellular space
*Seizure, coma, pulmonary edema most serious
*Thirst, fever, dry mucus membrane, restless
*Determine ECFV- is it normal, inc or dec?
*local or generalized
*can be gravity dependent
*Usually assoc w/ weight gain, swelling and puffiness, limited movement of affected area
*Inc tissue pressure may limit capillary blood flow and therefore slows healing
*fluid in the interstitial space (3rd space) is NOT AVAILABLE for metabolic process or perfusion
*dehydration from pure water deficit
*Volume depletion from both water and salt loss. See weight loss, extreme thirst, dry mucus membrane
*Decreased Vascular Perfusion from hypovolemic shock, vasodilatory shock, cardiogenic shock
Regulation of TBW
-Water follows sodium osmotic gradient. Sodium is regulated by the effects of aldosterone on the kidneys. Reabsorption of sodium by distal tubule of kidney. Renin and angiotensin inhibit aldosterone secretion. Water balance regulated by thirst and anti diuretic hormone (ADH). ADH release initiated by inc in plasma osmolality or decreased circulating blood volume.
-Sodium accounts for 90% of ECF cations
Major intracellular electrolyte found iin most body fluids
*ICF concentration of K is 150-160mEq/L and ECF is 3.5-4.5 mEq/L.
*Difference between ICF and ECF is maintained by Na/K pump. Ratio of ICF K to ECF K determinant of resting membrane potential which is important for nerve impulse, cardiac rhythm, and ms contraction
*Insulin causes K movement INTO cell
*Acidosis cause K to leave cell in exchange for H (opposite for alkalosis)
*Beta 1 receptor stim causes K shift INTO cells from increased pump action
*Alpha adrenergic stim shifts K OUT of cell
*aldosterone released from inc of K; sweat gland secretion of K.
*reduced K intake
*inc entry of K into cells
*inc body loss of K,
*alkalosis (most common problem)
*sweating, diarrhea, urine inc K loss
*Decreased insulin secretion
*Skeletal muscle weakness
*Smooth muscle atony
***onset of sx depends on rate of K depletion
Serum K>3.5. Rare due to efficient renal excretion
*Shift of K from cells to ECF. Occurs with cell trauma or change in membrane permeability like acidosis, fluid deficiency, or cell hypoxia. In acidosis, hydrogen ions shift into cell in exchange for K ions. Acidosis and hyperkalemia often occur together.
*Decreased renal excretion
*total body content is 1200g
*Serum level 8.6-10.5mg/dl
*99% contained within bone; remainder in plasma. *50% in plasma is bound to protein and 40% is *free/ionized (most important physiologic function)
*Major cation for structure of bones and teeth
*Enzymatic cofactor for blood clotting
*85% contained within bone
*serum inorganize phosphate 2.5-4.5mg/dl
*intracellular phosphate in many forms including ATP
*Ca and phosphate concentrations are DIRECTLY related; a constant
*Balance regulated by parathyroid hormone, vitamin D, and calcitonin
-Serum <8.5 mg/dl
*inadequate intestinal absorption
*deposition of ionized Ca into bone or soft tissue
*Decrease PTH and vit D
*Inc neuromuscular excitability, Chvostek and Trousseau sign, Tetany/convulsions
*bone mets with calcium reabsorption from various cancers
*Excess Vit D
-Manifestations (loss of cell membrane excitability): *Fatigue, weakness, lethargy, anorexia, nausea, constipation
Serum <2 mg/dl
*intestinal malabsorption. Vit D deficiency, long term alcohol abuse, use of antacids
*Inc renal excretion. Associated with hyperparathyroidism
*Reduced capacity for oxygen transport and disturbed energy metabolism, inc risk for infection, blood clotting impairment, muscle weakness.
*cell destruction associated with treating some cancers
*long term use of phosphate-containing enemas and laxatives
*related to hypocalcemia-similar sx (inc neuromuscular excitability)
*40-60% in muscle and bone
*30% stored in cells
*1% in serum
*plasma concentration: 1.8-2.4mEq/L
*Cofactor in tracellular enzymatic reactions, protein synthesis, nucleic acid stability, and neuromuscular excitabiliyt
-Caused by malnutrition, alcohol, malabsorption, metabolic acidosis, diuretic use
-Sx: depression, confusion, irritability, inc reflex, muscle weakness
*rare; caused by renal failure.
*See depressed skeletal muscle contraction and nerve function. Nausea, vomiting, muscle weakness, hypotension, bradycardia
-Hydrogen ion concentration expressed as pH
-As H inc, pH decreases. As H dec, pH inc
-Low pH>high H> acidic solution (opposite with high pH)
-Different fluids have different pH; arterial 7.38-7.42
-Intracellular/extracellular buffering occurs in response to change in acid-base status to maintain normal pH.
*Bicarbonate,Hemoglobin, Phosphate, plasma protein. All work instantaneously
*organ buffers are lungs, ionic shifts, kidneys, and bone
PRIMARY: pH<7.35, HCO3 normal, PCO2 high
COMPENSATED: pH<=7.35, but head to normal, *HCO3 high, PCO2 high
Caused by hypoventilation; depression of resp center, brainstem trauma, oversedation, disorders of chest wall, and disorder of lung parenchyma. Most common cause is airway obstruction
See: headache, restlessness, blurry vision, apprehension followed by lethargy. RR is rapid at first to blow off CO2, but then slow down as compensated. Renal buffering helps to return to norm
PRIMARY: pH <7.35, HCO3 low, PCO2 normal
COMPENSATED: pH <=7.35 but headed to normal, HCO3 low, *PCO2 low
compensated by hyperventilation. Caused by inc in noncarbonic acids or loss of bicarb. Can occur from poor perfusion or hypoxemia, renal failure or diabetic ketoacidosis.
See: headache and lethargy (early sx). Anorexia, nausea, vomiting, diarrhea. See deep rapid respirations to blow off CO2.
PRIMARY: pH>7.45, HCO3 normal, PCO2 low
COMPENSATED: pH>=7.45, but headed to normal, *HCO3 low, PCO2 low
Occurs within minutes of hyperventilation. precipitated by hypoxemia, from pulmonary disease, CHF, or high altitudes, fever, anemia, thyrotoxicosis, early salicylate intox, hysteria, cirrhosis, gram neg sepsis.
See: dizziness, confusion, paresthesias, convulsions, coma
PRIMARY: pH>7.45, HCO3 normal, PCO2 low
COMPENSATED: pH>=7.45, but headed to normal, HCO3 high, *PCO2 high
Usually caused by loss of acids as with prolonged vomiting, GI suctioning, excessive bicarb intake, hyperaldosteronism with hypokalemia, and diuretic therapy.
See: prolonged vomiting, weakness, muscle cramps, hyperactive reflexes, sx assoc with loss of electrolytes, slowed breathing to inc CO2 to compensate.
Useful to determine type of metabolic acidosis
*normal is related to bicarbonate loss with retention of chloride to maintain ionic balance
*elevated is accumulation of anions other than chloride.
*red blood cells transport hemoglobin which carries oxygen to tissues from the lungs.
*They carry carbonic anhydrase, which is a form of carbonic acid that catalyzes a reaction with CO2 and water. Allows RBC to carry CO2 in the form of bicarb to lungs to be expelled as CO2
*They have biconcave shape to allow them to squeeze through narrow openings
Shows function of erythropoietin. Total mass of RBC is controlled tightly so that there is enought RBC, but also there isn't too many so they don't clog.
Life span of RBC is 120 days. As this approaches, there's dec enzyme production (ATP,MCH), dec deformibility, spirocytosis, bound by IgG, and then ingested by macrophages in the spleen and extravasscular hemolysis. Iron is then relseased to transferrin in hgb and excreted as bilirubin.
Vitamin B12 and folic acid are required in the production of healthy RBC production. Lack may lead to pernicious anemia.
Body needs more RBC than it currently has/had due to change in health status causing poor tissue oxygenation or environmental change such as inc altitude.
Hematocrit: % volume of blood that is red cells (men 45%, Fe 40%)
Hemoglobin: binds to oxygen. 35gm/100 ml red cells. (male 15-16 gm Hb/100 ml blood; female 13-14 gm Hb/100 ml blood)
Oxygen carrying capacity: gm Hg/100ml blood*1.34 ml O2/gm Hb (male-21 ml; female-19)
RBC: male-5.4; female-4.8
WBC 7.8 +/- 3
Platelet count 140-440
Hgb male-16 female-14
Hct (+/- 5) male-47% female-42%
MCV- 90 +/- 9
MCH- 32 +/-2
MCHC- 33 +/-3
They work together to destroy organism by phagocytosis or form antibodies against it through sensitized lymphocytes
*Granulocytes (65%): neutrophils, eosinophils, basophils. Formed in bone marrow
*Monocytes (5%): tissue macrophages. formed in bone marrow
*Lymphocytes (30%): formed in lymph tissue
Granulocytes include neutrophils, eosinophils, basophils. These are granulated.
Non granulocytes are monocytes and lymphocytes
Poly: Neutrophils, eosinohils, basophils. These are multilobed and have nucleus.
Mono: monocytes and lymphocytes
Phagocytes consume other cells: neutrophils, monocytes, basophils; acrophages, eosinophils
Non phagocytes are lymphocytes.
WBC start with same cell as RBC. Granulocytes only live 4-8 hr in blood, but live 4-5 days in tissue that are site of infection. Monocytes swell to become tissue macrophages once they reach the tissue.
The more serious the infection, the faster WBC respond.
Platelets replaced every 10 days
-Polymorphonuclear neutrophils are non-dividing and short lived. Dominant number in blood
-Monocytes/macrophages are long-lived, do not circulate, present in tissue (esp in lung, spleen, liver, and lymph node), and tissue macrophage system.
**phagocytosis is MOST important function of neutrophil and macrophages
*Important in resistance to infection
2. inc capillary permeability
3. Clotting of interstitial fluid
4. Swelling of cells
*substances involved are bradykinin, histamine, serotonin, complement, coagulation factors, lymphokines. There's a "wall off" effect to protect rest of body.
1. Tissue macrophages that are already in tissue
2. Neutrophil invasion. There's margination, diapedesis, chemotaxis, and stimulation of bone marrow to release stored leukocytes, 4-5hrs
3. Macrophage proliferation. Invasion by circulating moncocytes (hrs to inc size)
4. Stimulation of granulocyte/monocyte production. Growth factors produced by tissue macrophages are TNF, IL-1, CSF
*2% of total WBC
*Active against parasite, skin disease, chronic infection
*Phagocytic and immunomodulatory, decrease inflammation
*0.5% of total WBC
*Basophils similar to mast cells
*Release primarily histamine, some bradykinin
*release due to binding of IgE
*Account for only up to 1% of circulating WBC's
*Basophilia-Response to inflammation and hypersensitivity reactions.
*Basopenia-Occurs in acute infections, hyperthyroidism, and long term steroid therapy
*Means to "stop the blood"
*Blood must be fluid; can leak if hole
*MUST coagulate at right time; needs to be rapid, localized, and reversible. If thrombosis (clot for no reason) occurs; that's inapproppiate coagulation
1. vascular constriction, 2. formation of platelet plug, 3. formation of blood clot, 4. growth of fibrous tissues
After clot is formed, it can be invaded by fibroblasts to allow connective tissue to replace or dissolve.
*Covers highly thrombogenic basement membrane
*uninjured endothelium does not bind platelets
*PGI2 (prostacyclin) and NO from ininjured endothelium inhibit platelet binding
*ADPase counters the platelet aggregating effects of ADP
Formed in bone marrow (15-350,000(
Production regulated by thrombopoietin from liver and kidney
Sequestered in spleen (30%)
Active cytoplasm: actiin+myosin, enzyme synthesis+storage of calcium, synthesis of prostaglandins, dense granules containing ADP/ATP, a-granules (fibrinogen, PDGF, vWF, fibronectin), and fibrin stabilizing factor
*Receptors: thrombin, ADP, epi, serotonin.
*Adhesion proteins: vWF, fibronectin, collagen, fibrinogen
*Coat of glycoproteins > adhesion to injured area
*phospholippids > activation of intrinsic pathway
*adenylate cyclase > cAMP > activate other platelets
-Collagen and microfibrillar protein (vWF)
-ADP released from damaged RBC and activated platelet
-Thromboxane from activated platelets
-Platelet activating factor from basophils
1. Subendothelial protein layer is exposed
2. Platelets bind to subendothelial vWF, and collagen via surface glycoprotein
3. Platelets swell
4. Release platelet agonists from granules
5. Generate thrombin
6. Activation of new platelets
7. Crosslinking of platelet aggregate by surface glycoprotein
8. Contractile elements pull fibrin threads to plug
1. Enzymatic cascade
2. Several serine proteases produced by liver and require vitamin K
3. 3 Protein cofactors (not enzymes)
4. Requires Ca
5. Localized to site of injury
6. Reversible via production of plasmin
Schema for conversion of prothrombin to thrombin and polymerization of fibrinogen to form fibrin fibers
Prothrombin uses Ca to form thrombin and acts as an enzyme to make fibrinogen into fibrinogen fibers
Extrinsic pathway for formation of prothrombin activator
Caused by tissue trauma. Tissue thromboplastin that leads to factor X activation which is rapid and explosive.
**after activation of factor X, the extrinsic and intrinsic pathway is similar
Intrinsic pathway formation of prothrombin activator.
Starts with blood trauma where there's exposure to collagen or activated platelets. Slower than extrinsic
Time it takes to form clot when tissue-thromboplastin is added
*12-14 seconds, test of extrinsic and common pathway, factor 2, 5, 7, 10. Vitamin K factors and warfarin therapy
Time to form clot when plasma-thromboplastin is added
*30 seconds, test of intrisic pathway and common pathway. Tests factor 8, 9, 11, but NOT 7.
*Good test for heparinized patients. Will be longer in warfarin treated patients
International normalized ratio
*INR= PT test/PT normal
*INR usually 0.9-1.3 for normal
*INR 2-3 on anticoagulation therapy (warfarin)
Level 150-300,000/ ul
*Thrombocytopenia caused by aplastic anemia, autoimmune
*Platelet function-myeloproliferative, uremia, drugs (aspirin, antibiotics), vWD
Reduction in total number of erythrocytes in circulating blood or decrease in quality or quantity of hemoglobin. Get decreased oxygen carrying capacity.
*Results from blood loss, impaired production, increased destruction or combination
*Sx: pale skin, pale mucus membrane, pale nail beds, conjunctiva, fatigue, weakness, dyspnea, and pallor
See large RBC with normal Hgb. Also termed as megaloblastic anemias.
*Defective DNA synthesis due to B12 or folate deficiencies. Coenzymes for nuclear maturation and the DNA synthesis pathway
*RNA process occur at a normal rate. Results in unequal growth of the nucleus and cytoplasm
*Anemias: pernicious and folate deficiency anemia
A macrocytic-normochromic anemia
*Caused by lack of intrinsic factor from gastric parietal cells that are required for B12 absorption.
*Results in vitamin B12 deficiency.
*See typical anemia symptoms: Nerve demyelination, loss of appetite, abdominal pain, beefy red tongue (atrophic glossitis), icterus, splenic enlargement
*Treatment: parenteral or high oral Vitamin B12
*Often unrecognized in older adults due to subtle onset
A macrocytic normochromic anemia
*Absorption of folate occurs in upper small intestine
*Not dependent on any other facilitating factor
*Similar to pernicious anemia except neuro sx
*Treatment req only daily oral folate
*Pregnancy/lactating women req inc folate
*Essential in decrease level of homocysteine, which is a risk factor for developing atherosclerosis
*See small RBC and decrease Hgb
*Characterized by red cells that are abnormally small and contain reduced amounts of hemoglobin
*Related to: disorders of iron metabolism, Porphyrin and heme synthesis, and Globin synthesis
*Anemias: Iron deficiency, Sideroblastic, Thalassemia anemias
*A microcytic-hypochromic anemia
*Most common anemia worldwide, affecting 1/5 of population
*Nutritional, metabolic, or functional deficiency
*SX: Early-fatigue, SOB, and weakness. Brittle, thin, coarsely ridged, spoon-shaped nails. A red, sore, painful tongue (glossitis)
*sx occur when Hgb 7-8 g/dl
*At risks are woman of childbearing age, chronically poor, children are greatest risk. Others are children affected by parasites, ulcer, preg, meds, surgery, dec stomach acid, eating disorders
*A microcytic-Hypochromic anemia
*Group of disorders characterized by anemia
*Altered micochondrial metabolism caussing ineffective iron uptake and resulting in dysfunctional hemoglobi synthesis
*Ringed sideroblasts in bone marrow are diagnostic. Sideroblasts contain iron granules that have not been synthesised into hemoglobin.
*Dimorphism *Leading cause is myelodysplastic syndrome. Also hereditary, alcohol, drug, copper def, and hypothermia/reversible
*Erythropoietic hemochromatosis (iron overload)
*Characterized by red cells that are relatively normal in size and hemoglobin content, but insufficient in number
*No common etiology
*Anemias: aplastic, posthemorrhagic, hemolytic, sickle cell, anemia of chronic disease
*This is a critical anemia. It's characterized by pancytopenia, which is a reduction of or absense of all three blood cell types resulting from failure or suppression of bone marrow to produce adequate amounts of blood cells; this is rare.
*Another condition associated with aplastic anemia is pure red cell aplasia in which RBCs are affected. This is rare and associated with autoimmune, viral, and neoplastic disorder; infiltrative disorder of bone marrow, renal failure, hepatitis, mono, and SLE.
*Fanconi is a rare genetic anemia characterized by pancytopenia resulting from defects in DNA repair.
A normochromic-normocytic anemia
*From acute blood loss from the vascular space.
*Initial manifestations depend on amount of blood loss.
*500ml loss; no sx *1000ml loss; may have tachycardia and slight drop in BP with postural change *1500ml loss; neck vein flat in supine pos, exercise tachy and postural hypotension *2000ml loss; cardiac output and arterial bp below normal, air hunger, rapid and thready pulse, cold/clammy skin*2500 severe shock, lactic acidosis, death
*A normochromic-normocytic anemia
*can be acquired or congenital
*Accelerated destruction of RBC
*Autoimmune hemolytic anemia, immunohemolytic anemia, warm antibody immunohemolytic anemia, drug-induced hemolytic anemia, cold agglutinin immunohemolytic anemia, cold hemolysin hemolytic anemia.
*A normochromic-normocytic anemia
*Mild to mod anemia seen in AIDs, rheumatoid arthritis, lupus erythematosus, hepatitis, renal failure, and malignancies
*Pathologic mechanisms; Decreased erythrocyte life span, ineffective bone marrow response to erythropoietin, altered iron metabolism
*Counts lower than normal.
*Low WBC predisposes to infections.
*Can be caused by radiation, anaphylactic shock, autoimmune disease, immune deficiencies and some chemos
*Evident in first stages of infection/inflammation
*If need for neutrophils increase beyond supply, immature neutrophils (banded) is released into blood
*Premature release detected in manual WBC diff and is termed a shift to the left or Leukemoid reaction
*Return to norm is shift to the right
*Reduction in circulating neutrophils
*Primary: Congenital. Cyclic neutropenia and neutropenia with congenital immunodeficiency diseases. Multiple syndromes.
*Acquired: Multiple conditions: hypoplastic anemia, aplastic anemia, leukemias, lymphomas, myelodysplastic syndrome
*Production can't keep up w/ demand.
*Cause: prolong severe infection, decreased production, reduced survival, abnormal neutrophil distribution and sequestration
*Causes: interference with hematopoiesis, immune mechanisms, chemotherapy destructin, ionizing radiation
*Sepsis caused by agranulocytosis often results in death within 3-6 days.
*Hypersensitivity reactions trigger release of eosinophilic chemotactic factor of anaphylaxis from mast cells
*Increased in allergic disorders
*Increased in parasitic invasions
*Decrease in circulation numbers of eosinophils
*Usually caused by migration of cells to inflammatory sites
*Other cause: Surgery, shock, trauma, burns, or mental distress.
*Monocytosis: Poor correlation with disease. Usually occur with neutropenia in later stage of infection. Monocytes needed to phagocytize organisms and debris
*Monocytopenia: very little know. Given prednisone treatment. Hairy cell leukemia
*Lymphocytosis: Acute viral infections (Epstein-Barr virus)
*Lymphocytopenia: immune deficiencies, drug destruction, viral destruction
*A malignant disorder of the blood and blood forming organs
*Uncontrolled proliferation of malignant leukocytes. Overcrowding of bone marrow. Decreased production and function of normal hematopoietic cells
*Presence of undifferentiated or immature cells; usually blast cells
*Rapid onset with short survival
*Predominant cell is mature but does not function normally
*Common in adults (70% asymptomatic)
*Suppression of humoral immunity
*Increased infection with encapsulated bacteria
Anemia, bleeding purpura, petechiae, ecchymosis, hemorrhage, infection, weight loss, bone pain, liver/spleen/lymph node enlargement, elevated uric acid
*Clonal disorder in that a single progenitor cell undergoes mallignant transformation
*Malignant transformation of a lymphocyte and proliferation of lymphocytes, histiocytes, their precursors, and derivatives in lymphoid tissues
*Two major categories: Hodgkin and Non-Hodgkin
*Found in lymph nodes; median age of dx: 38
*Represent malignantly transformed lymphocytes
*Necessary for dx, but not specific to Hodgkin lymphoma
*Classical Hodgkin lymphoma
*Nodular lymphocyte predominant lymphoma
*B cell in the germinal center that has not undergone successful immunoglobulin gene rearrangement but has undergone apoptosis
*Survival of cell may be r/t Epstein Barr Virus
Findings: Adenopathy, mediastinal mass, splenomegaly, and abdominal mass.
Lab: Thrombocytosis, leukocytosis, eosinophilia, elevated ESR, elevated ALP, paraneoplastic syndromes
Sx: fever, wt loss, night sweat, pruritus
*Generic term for group of lymphomas
*Lymphoma can be differentiated by etioloogy, unique features, and response to therapies
*Linked to chromosome translocations, viral/bacterial infections, environmental agents, immunodeficiencies, and autoimmune disorders.
*lack of Reed sternberg cells and other cellular changes not associated with Hodgkin
*Clonal expansion of B, T, and/or NK cell
*Changes in protooncogenes and tumor suppressor gene contribute to cell immortality; thus inc malignant cell
Platelet count <100,000
*<50,000-hemorrhage from minor trauma
Causes: Hypersplenism, autoimmune dis, hypothermia, and viral/bacterial infections that cause DIC
*Arise from dec production, inc consumption or both. **heparin is common cause of drug induced thrombocytopenia
*IgG antibody targets platelet glycoproteins
*Antibody-coated platelets are sequestered and removed from the circulation.
*One of the most common childhood bleeding disorders
*Manifestations: petechiae and purpura, progressing to major hemorrhage
*A thrombotic microangiopathy. Platelets aggregate, form microthrombi, and cause occlusion of arterioles and capillaries
*Chronic relapsing TTP-Seen more in kids, recurring every 3 weeks
*Acute idiopathic TTP- Seen more in females in 30's. Damage occurs to multiple organs
*Thrombocythemia is characterized by platelet counts >400,000/mm3
*Myeloproliferative disorder of platelet precursor cells. Megakaryocytes in the bone marrow are produced in excess
*Microvasculature thrombosis occurs
*Asymptomatic until >400,000
*Secondary may happen after splenectomy b/c of lack of storage space for platelets; inc circulating platelets. Usually see 3 weeks after
-platelet wall adhesion
-platelet platelet interaction
-platelet granules and secretion
-arachidonic acid pathway
*Qualitative alterations demostrate an increased bleeding time in the presence of normal platelet count
*Disorders result from platelet membrane glycoprotein and von Willebrand factor deficiencies
*Manifestations: petechiae, purpura, mucosal bleeding, gingival bleeding, and spontaneous bruising
*Disorders can be congenital or acquired
*Vitamin K deficiency: Vit k is necessary for synthesis and regulation of prothrombin, the prothrombin factors (2, 7, 11, 10), and proteins C and S (anticoagulants).
*Liver disease: Causes broad range of hemostasis disorders. Defects in coagulation, fibrinolysis, and platelet number and function
*A complex, acquired disorder where clotting and hemorrhage simultaneous occur from sepsis, trauma, cancer, blood transfusion, malignancies, infection, pregnancy complication, liver disease, intravascular hemolysis, hypoxia, and low blood flow states
*Result of inc protease activity in blood caused by unregulated release of thrombin with subsequent fibrin formation and accelerated fibrinolysis
*Endothelial damage is primary initiator
*Blockage of blood flow to organs, resulting in MOF
*magnitude of clotting may result in consumption of platelets and clotting factors; leading to severe bleeding. By activating the fibrinolytic system, person's fibrin degradation product and Ddimer level inc
*The amont of activated thrombin exceeds the body's antithrombins and the thrombin does not remain localized
*The widespread thromboses created cause widespread ischemia, infarction, and organ hypoperfusion. High mortality rate
*Clinical s/sx demonstrate wide variability
-Bleeding from venipuncture site
-Bleeding from arterial lines
-Purpura, petechiae, and hematomas
-Symmetric cyanosis of the fingers and toes
*Treatment is to remove the stimulus.
1. pulmonary ventilation, which means inflow and outflow of air between atmosphere and lung alveoli
2. diffusio of oxygen and carbon dioxide between the alveoli and the blood
3. transport of oxygen and carbon dioxide in the blood and body fluids to/from body's tissue cells
4. regulation of ventilation and other facet of respiration
Lining is filled with mucus and ciliated cells that work when particles are inhaled. Small not filtered are caught by mucus and moved by rhythmic beating of cilia. Walls also contain smooth ms that have sympathetic and parasympathetic pathways.
B-2 adrenergic and albuterol affect on respiration
B-2 adrenergic receptors activate bronchial smooth muscle that used to relaxation and dilation of the airways
*Albuterol is a B-2 adrenergic agonist that dilate bronchial airway circulating epinephrine and isoprotenerol activate b2 receptor endogenously. Muscarinic receptor lead to contraction/constriction of the airway
* alveolar ducts
* alveolar sacs
* alveoli-about 300million/lung. thin wall, but large surface area to allow diffusion of co2 and o2. Walls have pneumocytes that produce surfactant
Have cilia and sm ms like conducting zone, but also site of gas exchange. Also have macrophages to keep free of dust and debris.
1. tidal volume: the volume of air inspired or expired with each normal breath; 500ml in ea adult male.
2. Inspiratory reserve volume: extra volume of air that can be inspired over and above normal tidal vol when person inspires with full force; usu 3000ml
3. Expiratory reserve volume; max extra vollume of air that can be expired by forceful expiration after end of normal tidal expiration; 1100ml
4. residual volume is volume of air remaining in lung after most forceful expiration; 1200ml. Can't be measured by spirometry
1. inspiratory capacity: equals TV plus IRV. This is the amount of air a person can breath in, beginning at normal expiratory level and distending lungs to max amount (3500ml)
2. Functional residual capacity (or Equilibrium volume): Equals expiratory reserve vol plus residual vol. This is the amount of air remaining in lungs at end of normal expiration (2300ml)
3. Vital capacity equals insp reserve volume plus tidal vol plus expiratory reserve volume. Max air one can expel from lung after first filling lungs to max then expire at max (4600ml)
4. Total lung capacity is max vol which lungs can be expanded wit greatest poss effort. Equal to vital capacity plus residual vol. (5800ml)
1. lungs expand and contract by downward and upward movement of diaphragm to lengthen or shorten chest cavity and by elevation and depression of the ribs to inc and dec the anteroposterior diameter of the chest cavity.
2. During insp, diaphram contracts, then during exp, diaphragm relaxes and elastic recoil of the lungs expel air.
3. during heavy breathing, elastic forces aren't enought, so abdominal muscles give extra force. Also raising the rib cage help expand lung (external intercostals and expiration are internal intercostals)
1. Pleural pressure is th epressure of fluid in the thin space between the lung pleura and chest wall pleura. Usually slightly negative pressure b/c need sligh suction for lungs to stay in place, but during normal inspiration, there is more negative pressure created.
2. Alveolar pressure is the pressure of air in alveoli. When glottis is open and no air is flowing in/out, the pressures all equal atmospheric pressure; considered 0. The pressure in alveoli must fall below during inspiration. opp with exp.
3. Transpulmonary pressure is difference between alveolar pressure and pleural pressure.
Exchange of o2 and co2 between external environment and cells of body. O2 is transferred from alveolar gas to pulm capillary blood and throughout tissues Partial pressure-Driving force for diffusion of gases. Pressure of gas would have if alone in space. Total pressure of gas we breathe that comprised of o2, nitrogen and co2 is sum of the partial pressures of each individual gas. Ex: if alveolar po2 is 100, mixed venous is 40; the driving force to go into blood is 60. Diffusion coefficient is combo of diffustion coefficient and solubility of gas; if 20% more than that of oxygen, diffuse 20x faster.
Oxygen/Hgb dissociation curve: demonstrates a progressive inc in percentage of hemoglobin bound with oxygen as blood o2 inc, which is called the percent saturation of hemoglobin. At P50, Hgb is 50% saturated; after that, less affinity for oxygen.
2 Forms of oxygen in blood: dissolved: free in sol 2% and Bound to Hgb: 98% reversibly bound.
Each Hgb can bind 4 molecules. % saturated is function of the partial pressure of oxygen of the blood is described by this curve.
At 100, Hgb is 100% saturated. Alveolar air, pulmonary capillary blood, and systemic arterial blood; oxygen is 100mmHg partial pressure.
Mixed venous has Po2 of 40, which is 75% saturated and lower affinity to oxygen; helps deliver oxygen to tissues because affinity not as great
Quantitatively the most important form of Co2; 70% of carbondioxide transporeted from tissue to lungs.
*First carbon dioxide reacts with water to form carbonic acid; carbonic anhydrase catalyzes the reaction between carbon dioxide and water; Carbonic acid is formed in the red cells and dissociates into hydrogen and bicarb ions. H ions then combine with Hgb and many of the bicarb ions diffuse from rbc to plasma. The reversible combo of Co2 with water under influence of anhydrase accounts for 70% of co2 transported from tissue to lung.
*Accounts for 23% of transported Co2.
*Carbon dioxide reacts directly with amine radicals of hemoglobin to form carbaminohemoglobin; a reversible reaction that is loosely bound so Co2 is easily released into alveoli where Pco2 is lower than in pulmonary capillaries.
Pulmonary vessels: Pulmonary artery divides into right and left main branches that supply blood to lungs. The pulmonary veins empty blood into left atrium. Pulmonary artery accomodates stroke volume of the right ventricle.
*Alveolar Po2 Dec r/t dec barometric pressure
*Arterial Po2 dec r/t hypoxemia
*Ventilation rate inc r/t hypoxemia
*Arterial Ph inc (resp alk r/t hypervent)
*Hgb conc inc r/t inc rbc conc
*2,3 DPG conc inc
*O2 hgb dissociation curve; shift to right
*Pulmonary vasc resistance; inc r/t hypoxic vasoconst
*Pulmonary arterial pressure; inc r/t inc pulmonary resistance
No blood flow during all portions of cardiac cycle b/c of the local alveolar capillary pressure in that area of lung never rises higher than alveolar air pressure during any part of cardiac cycle. Lowest blood flow.
Pressures driving blood force:
(PA=alveoloar pressure Pa=arterial pressure Pv=venous pressure)
Intermittent blood flow only during peaks of pulmonary arterial pressure b/c systolic pressure is greater than alveolar pressure, but diastolic pressure is less than alveolar air pressure. Medium blood flow
Highest blood flow. Continous blood flow b/c the alveolar capillary pressure remains greater than alveolar air pressure during entire cardiac cycle
*Ratio of alveolar ventilation to pulmonary blood flow
Matching ventilation to perfusion is important for ideal gas exchange
Normal value for VQ is 0.8; means alveolar ventilation is 80%. 0.8 avg for entire lung. Perfusion and pressure and VQ vary in different zones
Zone 1: blood flow lowest; alveolar vent; lower, VQ: highest, Pao2: highest, Paco2: lower
Zone 2: n/a
Zone 3: Blood flow: highest, Alveolar vent: higher, VQ lowest, Pao2: lowest, Paco2: higher
*Cough; acute-resolves in 2-3 weeks. Chronic->3 weeks *dyspnea-feeling of not getting enough air. see nasal flaring, use of accessary ms and retraction. *Pain-originates in pleurae, airway, or chest wall; inflammation *Sputum-color, consistency, odor, and amount vary *Hemoptysis-coughing up blood *Abnormal breathing patterns: Kussmaul-inc RR. Cheyene-Stokes; deep/shallow breathing and dec blood flow to brain stem. Apnea lasts 15-60sec. *Hypo/hypervent *Cyanosis *clubbing of fingers
*Hypercapnia (inc co2 in blood caused by hypovent. Dec RR from drugs/trauma. Neuron change that impact resp ms, structure, obstruction, and emphysema *Pulmonary edema (inc water in lung)
*Hypoxemia (dec oxygen of arterial blood***Hypoxia is reduced oxygen in CELLs in the tissue
*Acute respiratory failure (inadequate gas exchange. Caused by injury to lung or brain; underlying pulmonary disease, surgery, smokers, limited cardiac reserve, chronic renal failure, chronic hepatic disease, infection, atelactasis, pneumonia, pulm edema, and emboli)
1. Valvular dysfunction; CAD; L vent dysfunction--leads to inc left atrial pressure---leads to inc pulmonary capillary hydrostatic pressure---pulm edema.
2. Injury to capillary endothelium--lead to inc capillary permeability and disruption of surfactant production--leads to movement of luid and plasma protein from capillary to interstitial space and alveoli--pulmonary edema
3. Blockage of lymph vessels--lead to inability to remove excess fluid from interstitial space--accumulation of fluid--pulmonary edema
These are characterized by decreased compliance of lung tissue making it harder for lung inflation. Have c/o dyspnea and inc rr and dec tidal volume. See hypoxemia
Causes: Aspiration, Atelectasis, Bronchiectasis, Bronchiolitis, Pulmonary fibrosis, Pulmonary edema, ARDS
*A passage of fluid and solids into the lungs. Right lung more susceptible. Tends to occur in those whose normal swall mech and cough reflex are impaired by decreased LOC, or central nervous sytem abnormalities. 10% of community acquired pneumonia and up to 30% of admissions for pneumonia in those in long term facilities is result of aspiration.
*The collapse of lung tissue. Three types:
1. compression-caused by external pressure such as tumors or fluid
2. absorption-caused by gradual absorption of air from obstructed or hypoventilated alveoli or concentrated oxygen or anesthetic agent
3. surfactant impairment-from dec production or inactivation of surfactant.
*Seen after surgery. See dyspnea, cough, fever, leukocytosis.
*A persistent abnormal dilation of the bronchi. See with other conditions associated with bronchial inflammation. They can by CYLINDRICAL with symmetrically dilated airways as can be seen after pneumonia and is reversible. Also SACCULAR in which bronchi become large and balloon like. Then VARICOSE in which constrictions and dilations deform the bronchi. Primary sx is productive cough.
*Inflammation of the small airway or bronchioles. Most common in children. Seen in adults with resp virus. See rapid vent rate, use of accessory ms, low grade fever, dry/non prod cough, hyperinflated chest.
*Bronchiolitis obliterans: late stage fibrotic disease of airways. Can occur with all causes of bronchiolitis. Most common after lung transplant complicated by pneumonia. High morbidity
*An excessive amount of fibrous or connective tissue in the lung. Causes can be inhalation of harmful substances, autoimmune disease like rheumatoid disease. Can be idiopathic with no known cause.
-Restrictive; Also known as non-cardiogenic pulmonary edema
*A fulminant form of respiratory failure characterized by acute lung inflammation and diffuse alveolocapillary injury.
*Injury to the pulmonary capillary endothelium
*Inflammation and platelet activation
*Characterized by airway obstruction that is worse with expiration. Common sx is dyspnea and wheezing.
Asthma, chronic bronchitis, emphysema
-Obstructive; if one has emphysema with this, it's COPD
*Hypersecretion of mucus and chronic productive cough that continues for at lease 3 months of the year (usually winter months) for at least 2 consectuve years; seen more in smokers and exposure to air pollution. Inspired irritants inc mucus production and the size and number of mucous glands. Mucus is thicker than normal.
-Obstructive; if with chronic bronchitis, considered COPD
*Abnormal permanent enlargement of gas exchange airways accompanied by destruction of aveolar walls without obvious fibrosis leading to respiratory collapse. Inherited usually, but also from cigarettes, inhaled toxins, and air pollution. There's loss of elastic recoil
*Chronic disorder of the airways that involves a complex interaction of airway obstruction, bronchial hyperresponsiveness and an underlying inflammation. Leads to coughing, wheezing, breathlessness, chest tightness. Occurs at all ages and can be familial. 1/3 of those w/ allergic rhinitis also have asthma. 1/2 of cases occur during childhood. Causes also by air pollution, cigarettes, allergen exposure, urban residence, obesity, respiratory viral infections.
Pathologic lung changes consistent with emphysema, or chronic bronchitis. 4th leading cause of death in US; 6th worldwide
*Caused mainly by smoking and smoke exposure
Emphysema and bronchitis start with irritant or inherited a-1Antitrypsin deficiency that leads to release of cytokines, thus inc inflammatory response. Emphysema caused from inc protease activity with breakdown of elastin in connective tissue of lung and Chronic bronchitis from continuous bronchial irritation.
-Mild and self limiting
-Can set stage for bacterial infection.
-Virus destroys ciliated epithelial cells and destroy goblet cells and bronchial mucus glands.
-Risks: inc age, immunocompromised, lung disease, alcoholism, others
**above common in AIDS/HIV
Fungi, respiratory viruses, protozoa, and parasites
Infection caused by M. tuberculosis
-Usually affects lung, but may invade other body parts. Immune response isolates bacteria in tubercles with scar tissut. Bacilli may remain dormant for life in tubercles. Can become active during immunosuppression.
-Acid-fast bacillus -Airborne transmission
-tubercle formation -Caseous necrosis
-pos tuberculin test.
-Occlusion of a portion of the pulmonary vascular bed by a thrombus, embolus, tissue fragment, lipid, airbuble, or amniotic fluid
-Pulmonary emboli common arise from DVT from deep veins of thigh
-Triad of Virchow: Venous stasis, hypercoagulability, and injuries to endothelial cells that line the vessels
More common in woman. COPD most common disease associated with this.
-Normal pulm artery pressure is 15-18mmHg. PAH: mean pressure is >25 at rest or >30w/ exercise
*Cor pulmonale -secondary to PAH -R ventricular enlargement -CO fails with exercise; may be fine at rest -chest pain
-#1 cancer killer. More common in blacks and survival rate lower. Most common cause is cigarette and #2 is radon exposure (silent killer).
2 major categories:
1. Non-small cell: 75-85% of all lung cancers. Includes adenocarcinoma (tumor from glands) and squamous cell carcinoma (located centrally near hilus and project into bronchi). Large cell undifferentiated.
2. small cell: 15-20% of lung CA. Largest correlation with cigarette smoking and worst prognosis
Causes of Respiratory Acidosis
Causes of Respiratory Alkalosis
3 Common Causes of Metabolic Acidosis
2. Renal failure
Causes of Metabolic Alkalosis
-Dependent on location of alteration
-Hypoxia, Hypoglycemia, Toxins or drugs
*Four different histamine receptors; H1, H2, H3, H4
*Release of histamine is an important mediator of immediate allergic and inflammatory responses
*Often the first agents used to prevent or treat allergic reactions
*Used for motion sickness and vestibular disturbances
*Historically used for "morning sickness"
*First generation have more AE (ex diphenhydramine, terfenadine, chlorpheniramine, clemastine)
*Early second generation have significant drug-drug interactions
*Late second generation include cetrizine and fexofenadine
*Taken off market in '98 due to QT prolongation and ventricular arrythmias
*Some agents (Erythromycin and Ketoconazole) inhibit CYP3A4's metabolism of terfenadine
*Grapefruit also inhibits CYP3A4 activity
*Benadryl (first gen)
*Dose 25-50 mg q 4-6 hrs prn. Max 300mg qd
*Availble in: tabs, caps, oral disintegrating tabs, chewable, soft gel caps, elixir, strips, solution, syrup, inj, cream, gel, topical
*preg risk B
*Claritin (2nd gen) *Available in tabs, syrup
*dose 10mg qd *preg risk B
*Drugs that inhibit the metabolism of this include amiodarone, clarithromycin, ketoconazole, and anti retroviral protease inhibitors. Increased concentrations of loratidine could lead to QT prolong
*TAke on empty stomach (1hr before/2hr after meal)
*Advise to stop taking 4 days before skin test; can mask pos response
*Zyrtec (2nd gen)
*Dose 5-10mg daily
*available in tab, syrup
*preg risk B
*Avoid coadministration with grapefruit juice
*D/c 4 days prior to skin test
*coffee/tea may dec drowsiness
*SALAD: xanax, zantac
*Clarinex (2nd gen)
*Dose 5 mg daily
*available in tabs, oral liq
*Preg Risk C
*dose 60mg bid
*available in capsule
*Preg risk C
*Possible interference with skin test. d/c 24-48hrs before
*Avoid giving with grapefruit juice
RIGHT-RIGHT-RIGHT: examiner stands on patient's right, holds light in right hand to look at right eye; LEFT-LEFT-LEFT
starts ~12inches from pt's eye, moving to 1-2in.
obtain red reflex, then look for optic disc, end with fovea (macula) of each eye