Lec5-6 Hemodynamics Flashcards
1
Q
Distribution of water in body– percent of body mass? Intracellular vs interstitial vs intravascular?
A
Body is 60% water by mass:
40% intracellular [in cell]
15% intercellular or interstitial [between cells]
5% intravascular [in blood vessels]
2
Q
Normal plasma osmolality? Major osmole? Osmolarity intracellular vs intercellular vs intravascular?
A
280 mosm/L
major osmole is sodium
electrolytes, glucose, proteins, urea also contribute
Intravascular, interstitial, intracellular spaces always have equal osmolarity
3
Q
Osmosis– definition? 2 requirements for osmosis to occur?
A
Fluid moves from one chamber to equalize osmotic gradient
2 requirements:
1. driving force [difference in osmolarity]
2. semipermeable membrane
4
Q
Water and molecule movement and distributions – what can move where (between intracellular, intercellular, intravascular?
A
- water moves freely between intravascular, interstitial, intracellular so always equal osmolarity
- small solutes move through clefts in blood vessel endothelium between intravascular and interstitial [together = extracellular] so always same concentration of small solutes
- small solutes can’t pass through cell membrane so have conc. gradient between intra and extracellular
- large molec [proteins] and cells do not move freely, trapped inside cell or inside intravascular space so get concentration gradients
5
Q
Effect of half normal vs normal saline fluid on hypotensive patient
A
Half normal: decreases osmolarity of intravascular space, so water moves to intracellular/intrerstitial space to equalize osmotic pressure, all 3 spaces expand a little
Normal: osmolarity of intravascular stays the same, water and electrolytes move to interstitial to equalize concentration gradient, extracellular spaces expand [by more than for half normal]
Normal saline = better treatment for increasing intravascular volume
6
Q
Starling’s Equation
A
Jv = Kf * [(Pc + Πi) – (Πc + Pi)]
- Jv = fluid movement in ml/min
- Kf = hydraulic conductance, easyness of getting out of tube
- Filtration [movement out] = (Pc + Πi)
- Pc = outward hydrostatic P by blood in capillary
- Πi = outward oncotic P by proteins in interstitium
- Absorption [movement in] = (Πc + Pi)
- Πc = inward oncotic P by proteins in capillary
- Pi = inward hydrostatic P by interstitium
7
Q
How does fluid end up in wrong place? [4 Mech]
A
When filtration > absoprtion
- low Πc: hypoalbuminemia, lose protein in urine
- – nephrotic syndrome, hepatic cirrhosis, malnutrtion [kwashiokor] - high Pc: heart failure
- – right sided = peripheral edema
- – left sided = pulmonary edema - high Kf: sepsis and inflammation
- – capillary leak syndrome in meningitis - lymphatic impairment [from surgery, mechanical]
- – increased interstitial fluid
- – increased Πi
8
Q
Cause/effect of low capillary oncotic pressure
A
caused by hypoalbuminemia = losing protein in urine
get more filtration than absorption, fluid leaves intravascular = edema
9
Q
Cause/effect of high capillary hydrostatic pressure
A
caused by heart failure
- right sided heart failure –> peripheral edema
- left sided heart failure –> pulmonary edema
10
Q
Cause/effect highly permeable blood vessels
A
- High Kf [hydraulic conductance] due to sepsis and inflammation
- ex. capillary leak syndrome in meningitis
11
Q
Cause/effect impaired lymphatics
A
- due to surgery or mechanical reason
- extra filtrate in interstitial space can’t get returned to circulatory system
- get increased interstitial fluid
- get increased Πi
12
Q
Definition of Edema
A
- Too much interstitial [intercellular] fluid
- Can be localized or generalized
- different from hydropic change/cell swelling which is intracellular edema
13
Q
Definition of Anasarca
A
generalized edema
14
Q
Definition of Effusion
A
type of edema - excess fluid in body cavity
15
Q
Definition of Hydrothorax
A
- Pleural Effusion
- Excess free fluid in pleural cavity
16
Q
Causes of Transudate
A
- high intravascular hydrostatic P [high Pc]
- – cardiac/vascular problem, deep vein thrombus, congestive heart failure
- low intravascular osmotic P [low Πc]
- – low plasma protein, nephrotic syndrome, chronic liver disease, protein malnutrition
- Lymphatic obstruction [high Πi]
- – inflammation, post-surgical, tumor
- Excess body fluid due to Na retention in setting of renal dysfunction
- increase Na intake –> retention water
17
Q
What is Dependent pitting edema? Exudate or transudate? 3 main Causes?
A
- swelling occurs underneath skin usually in arms/legs/ankles, can be depressed
- transudate edema
- due to congestive heart failure, pulmonary edema, renal disfunction
18
Q
What is Hemostasis? Functional components?
A
Arrest of hemorrhage in response to vascular injury Functional components: - blood coagulation - platelet aggregation - endothelial cell interaction
19
Q
What is Hemorrhage
A
bleeding, escape of blood from vessels
20
Q
What is a Hematoma
A
localized collection of blood [usually clotted] within tissue or space
21
Q
What is Thrombosis
A
Active process of transformation flowing liquid blood to semisolid in heart/vessel of living organism
22
Q
What is a Thrombus
A
coagulated blood containing platelets, fibrin, entrapped cellular elements
23
Q
Blood coagulation pathway steps
A
- vessel severed/injured
- plasma in vessel contacts tissue factor [TF]
- TF binds factor VII and activates it
- active VIIa-TF complex activates factor X
- Xa converts prothrombin –> thrombin and fibrinogen to fibrin
- VIIa-TF activates IX to amplify thrombin generation through intrinsic pathway
Fibrinolysis controls size of thrombus
24
Q
What is Tissue Factor
A
extrinsic to blood, plays key role in initiating coagulation
25
Are coagulation factors present in blood in absence of injury?
Yes -- in inactivated form
26
Inhibitors of platelet aggregation?
- Prostacylin [PGI2] and Nitric Oxide [NO] released by epithelial cells
- Antithrombin III: binds heparin like molec on epithelial cell surface --> inactivates thrombin, factors Xa/IXa
27
Role of platelets in thrombosis
- form initial hemostatic plug
| - release Ca, ADP, Thromboxane A etc that attract more circulating platelets to site of injury
28
Virchow's triad
Causes of thrombosis
1. endothelial injury
2. alteration in flow
3. hypercoagulable blood
29
Cause of endothelial injury?
Most important for arterial thrombus
- ruptured atherosclerotic plaque
- inflamed cardiac valve [endocarditis]
- inflamed vessel [vasculitis]
- MI
- hypertension, turbulent flow, bacterial products
30
Most likely cause arterial thrombus
injured endothelium
31
Most likely cause venous thrombus
altered flow - obstruction
32
Cause of altered flow?
- anuerysms
- atherosclerotic plaques
- atrial fibrillation
- dilated cardiac ventricles
- obstruction = particularly important in venous thrombus
33
Cause of hypercoagulable blood?
primary: inherited coagulation factor or inhibitor abnormality
- factor V leiden -- alternate form favor V that can't be inactivated by activated protein C
- prothrombin gene mutation
- Protein C or S deficiency
- Antithrombin III deficiency
- Homocysteinuria
secondary
- oral contraceptives
- pregnancy
- cancer
- polycythemia
- antiphospholipid antibody syndrome
34
Thrombin-Thrombomodulin rxn
- Thrombin binds thrombomodulin on epithelial cell surface and activates protein C
- active protein C with protein S cause proteolysis of Va and VIIa
35
Lines of zahn
- alternating layers of paler fibrin/platelets and red blood cells
- indicated thrombus that formed in flowing blood
- allows you to differentiate from clot
36
Clot
- Blood solidified OUTSIDE vascular system or has solidified in blood vessels POSTMORTEM
37
Thrombus vs clot
- Clot not attached to wall of vessel
- "Chicken fat" appearance of plasma in clot
- "Currant jelly" appearance of RBCs in clot
- No lines of zahn in clot
38
5 Possible outcomes thrombus
- propagation
- lysis
- organization and recanalization
- become infected
- embolize
39
embolus
sold, gas, or liquid other than liquid blood that travels through vessels and lodges somewhere
40
5 types of emboli
- thromboemboli
- atheroemboli
- fat
- air
- tumor
41
Thromboemboli
- Most common = pulmonary thromboembolus
- most common source = deep leg veins
- possible manifestations
- -- asymptomatic
- -- sudden death [saddle embolus]
- -- pulmonary hemorrhage/infarction
- -- chronic pulmonary hypertension
42
Arterial Embolus
- Embolus ends up in the systemic circulation
| - Cause occlusion blood vessels in systemic organs [brain, heart, etc] or lower extremities
43
Paradoxical Embolus
- thrombus forms in vein and travels through patent foramen ovale into artery and enters systemic circulation
- normally if no patent foramen ovale would have traveled to lungs first and get pulmonary embolism
44
Atheroemboli
Debri from ruptured atherosclerotic plaque embolized from aorta to brain, kidney, toes, etc
45
Air Embolism
Caused by
- delivery through ruptured vein
- chest trauma
- cardiac surgery
- decompression sickness
46
Fat Embolism
- after fracture or orthopedic surgery --> fat from marrow released into circulation
- lipid obstructs vessels, releases fatty acids causes endothelial injury
- pulmonary fat emboli cause edema, diffuse respiratory dysfunction
- can also embolize to brain/kidneys/heart
47
Infarction
Area of irreversible tissue necrosis due to ischemia
48
Ischemia
imbalance of oxygens supply and demand due to loss of blood flow from obstructed arterial flow or reduced venous drainage
49
White infarct
- due to arterial occlusion
- single blood supply
- not reperfused
- wedge shaped area of infarction
- solid tissue
- kidney, heart, spleen
50
Red infarct
- due to venous occlusion
- dual blood supply
- reperfused
- loose tissue
- brain, lungs, liver, GI tract, testicular torsion
51
Disseminated Intravascular Coagulation
- excessive secondary activation of coagulation leads to thrombus formation in microvasculature
- causes micro-infarction of multiple organs
- uses up/depletes clotting factors and platelets
- leads to hemorrhage, bleeding diathesis [ high susceptibility to bleeding]
- uncontrolled hemorrhage may lead to shock
52
Causes of DIC [disseminated intravascular coagulation]
- Release of TF - tumors, tissue injury, obstetrical complication
- Endothelial injury
- Bacterial Sepsis - IMPORTANT FOR QUIZ
- Burns
53
DIC [disseminated intravascular coagulation] pathology in tissues
- many venules/capillaries/arterioles have fibrin-platelet thrombi
- ischemic changes in many organs --> multi-organ failure
schistocytes in blood
54
Schistocytes
- fragmented RBCs
- sign of microangiopathic hemolytic anemia
- sign of DIC [disseminated intravascular coagulation]
55
Diagnosis DIC
Laboratory
- decreased platelets + fibrinogen
- prolonged lab tests of coagulation [takes long time for blood to clot in test tube]
- fibrin-split products in blood [product of plasmin degradation of fibrin thrombus]
Morphology
- schistocytes on peripheral blood smear
- fibrin-platelet thrombi histologically
56
Treatment DIC
- Treat underlying disease
| - Heparin
57
Shock -- 3 causes?
circulatory collapse = global hypotension with widespread hypoperfusion of tissues
3 Causes
- cardiogenic [MI, arrhythmia]
- hypovolemic [hemorrhage]
- septic [microbial infection]
58
Effect of hypoperfusion
- lactic acidosis [low pH]
- hypotension
- tissue ischemia and necrosis
- multi-organ system failure
59
Septic shock
- secondary to infection [ usually gram + or -]
- bacterial products / inflammatory mediators --> vasodilation and increased vascular permeability
- often leads to DIC
60
Compensated shock
- normal BP, no urine output
- tachycardia
- peripheral vasoconstriction in hypovolemic/cardiogenic shock
- recovery possible
61
Decompensated shock
- low BP
- widespread tissue hypoperfusion/hypoxia --> lactic acidosis
- renal insufficiency
62
Irreversible shock
- low BP, lactic acidosis, organs die
| - leads to death
63
Pathology of shock
- necrosis of areas farthest from arterial supply
- -- centrilobular necrosis liver
- -- mucosal necrosis intestines
- -- subendocardial necrosis of heart
- necrosis of vulnerable cells
- -- diffuse hypoxic neuronal injury of brain
- -- epithelial necrosis of kidney
64
Does ADP inhibit or promote thrombus formation?
Promotes -- ADP is released from platelets when they are activated and cause activation of other platelets for aggregation to form thrombus
65
Thromboxane A2
Produced by activated platelets, promotes activation of more platelets and thrombus formation
66
What is the effect of high hydrostatic pressure?
get heart failure
- - left --> leads to pulmonary edema
- - right --> leads to passive congestion in liver, periphery/limbs [generalized edema]
67
What is the cause of low oncotic pressure
- not taking in enough [malnutrition]
- peeing too much [nephrotic sundrome]
- protein losing enteropathy
- inflammation from infection, tumor, sarcoidosis
68
What is protein losing enteropathy
- condition of GI tract that results in net loss of protein from body
- causes: crohn's, celiac, amyloidosis,
69
What is in transudate? Cell content, Protein, specific gravity, endothelial intact or not intact, etiology?
- no cells
- not much protein
- specific gravity < 1.012
- intact endothelium, ultrafiltrate
- due to F. S. equation mechanisms
70
What is in exudate? Cell content, Protein, specific gravity, endothelial intact or not intact, etiology?
- lots of cells mostly neutrophils
- lots of protein
- specific gravity > 1.020
- endothelium not intact, increased vascular permeability
- due to infection
71
Is transudate associated with increased vascular permeability?
NO!!!
72
What are 5 inherited diseases that lead to hypercoagulation?
- factor V leiden -- alternate form factor V that can't be inactivated by activated protein C
- prothrombin gene mutation
- Protein C or S deficiency
- Antithrombin III deficiency
- Homocysteinuria
73
What is factor V leiden?
alternate form of factor V that can't be inactivated by activated protein C
74
What is the antigen in goodpastures?
Collagen IV in glomerular basement membrane
