Lecture 4.1 MJ slides Flashcards
List conditions with venous return issue-related edema
Too much pressure:
1) Congestive heart failure: pump isn’t working so fluid is backing up in venous system, some starts to leak out
2) Constrictive pericarditis: same as above
3) Ascites (liver cirrhosis): impeding flow in liver = backing up in venous system, = ^ pressure
4) Venous obstruction or compression : impeding flow
5) Thrombosis: impeding flow
6) External pressure (mass/cancer) : impeding flow
7) Lower extremity inactivity – dependency
List conditions relating to an oncotic pressure source of edema
1) Solute is gone: fluid leaks out, hydrostatic force wins too much
2) Protein-losing glomerulopathies (nephrotic syndrome): not enough albumin
3) Liver cirrhosis: (albumin!)
4) Malnutrition
5) Protein-losing gastroenteropathy: solute is gone
Lymphatic obstruction causing edema; what is it? Give 4 examples
Drain is broken
1) Inflammatory dz
2) Neoplasm: cancer in lymph. system
3) Post surgical: drain is missing
4) Postirradiation: impede flow
List conditions involving sodium retention-related edema
Water follows salt
1) Too much salt, too little kidney function: water follows salt, volume is super high & leaking out
2) Increased Na+ uptake
3) Renal hypoperfusion: if kidneys think they’re being starved of oxygen, they keep salt
4) Increased renin-angiotensin- aldosterone secretion: causes kidneys to ask for more salt
What should you think abt when you hear “sodium”?
Blood volume
List types of inflammation that can cause edema
1) Acute inflammation
2) Chronic inflammation
What can go wrong with medical clotting inhibition?
1) Factor V Leiden Mutation
2) Protein C and S deficiency
3) Antithrombin III deficiency
4) Von Willebrand’s disease
How do we intervene on other pathology with medicines that act on hemostasis? (use an example)
Blood Clots and Cardiovascular Disease:
1) Anticoagulate with heparin or NOAC now called (DOAC)
2) Use ASA or P2Y12 inhibitors for antiplatelet therapy
3) Lyse clot with tPA
List 13 conditions that cause hypercoagulability
1) Factor V Leiden mutation
2) Anti-thrombin III deficiency
3) Protein C and S deficiency
4) Immobility!
5) Cancer!
6) Surgery!
7) Tissue injury!
8) Prosthetic valves
9) Anti-phospholipid antibody syndrome
10) Smoking
11) Atrial fibrillation!
12) Pregnancy and postpartum
13) Oral contraceptives (esp. if smoking over 35)
Hypercoagulability causes:
1) Which condition turns up the thing that makes you clot?
2) Which two conditions turn down the thing that stops clotting?
3) Which 3 reasons cause hypercoagulability because of internal damage?
1) Factor V Leiden mutation
2) Anti-thrombin III deficiency
Protein C and S deficiency
3) Surgery, tissue injury, anti-phospholipid antibody syndrome (attack against blood vessels)
Hypercoagulability causes:
1) Which two conditions cause sticky blood?
2) Which two reasons involve estrogen’s sticky nature?
3) Why can cancer and prosthetic valves both lead to hypercoagulability?
1) Immobility + atrial fibrillation (afib)
2) Pregnancy and postpartum + Oral contraceptives (esp. if smoking over 35)
4) Both are sticky
Systemic thromboemboli refers to what emboli?
Emboli in circulation
1) 80% of arterial thrombi arise from what?
2) Give examples
1) Intracardiac mural thrombi
2) Left ventricular wall infarcts
Dilated left atria secondary to mitral valve defects
Aortic aneurysm
Atherosclerotic plaque
1) Arteriolar embolization often causes what?
2) Major sites for venous emboli are ________extremities
1) Tissue infarction
2) lower
Fat embolisms
1) Name 2 causes
2) What are the Sx?
3) When is Sx onset and which Sxs come first?
1) Long bone fracture or intramedullary reaming under tourniquet
2) May be asymptomatic, or may have a myriad of symptoms (<10%), especially pulmoriary insufficiency.
3) 1-3 days after injury with sudden onset of dyspnea, tachycardia, irritability, and restlessness
Amniotic Fluid Embolism (via tears in placental membrane or uterine vein rupture):
1) What is it?
2) Mortality?
3) Sx?
4) What happens to survivors of this?
1) Uncommon, grave complication of labor occurring in the immediate post-partum period.
2) 80% mortality, accounts for 10% of maternal deaths, survivors almost always suffer permanent neurologic deficits
3) Onset is sudden with severe dyspnea, cyanosis, and hypotensive shock seizures and coma
4) Pulmonary edema; 50% get DIC secondary to prothrombotic in amniotic fluid
Air Embolism:
1) What is it?
2) When is it seen most?
1) Gas bubble coalesce to form occlusion that can cause ischemic injury
2) Mostly from surgical procedures like laproscopy
Factor V Leiden:
1) What is its inheritance?
2) What exacerbates it?
3) What is the demographic?
1) Autosomal dominant [gain of function] with incomplete penetrance
2) Exacerbated by environmental factors
3) Low incidence in Black and Asian and higher among Whites
Factor V Leiden: what are 2 signs on physical exam?
1) DVT
2) Possible PE
1) What factor accelerates clotting?
2) What is the inheritance risk of Factor V Leiden if one parent carries a mutant allele?
1) Factor V accelerates clotting
2) 50% risk of child getting it with 10% penetrance, so a 5% lifetime risk
Heparin induced thrombocytopenia (HIT):
1) Who does it happen to?
2) What is occurring?
3) What does this result in?
4) What state does this lead to?
1) Up to 5% of patients who get heparin
2) Autoantibodies bind to complexes of heparin and platelet membrane protein and endothelial surfaces
3) Platelet activation, aggregation, and consumption; also causes endothelial injury
4) PROTHROMBOTIC state!
Why is PT/INR PTT always required for baseline before starting heparin?
Heparin induced thrombocytopenia (HIT)
Disseminated Intravascular Coagulation (DIC)
1) When does it occur?
2) What is it?
3) What is activated at the same time? What does this lead to?
1) It occurs in some severe sepsis / shock, obstetric complications, advanced malignancy
2) This is wide-spread clotting in the microcirculation all over the body
3) Fibrinolytic mechanisms; profuse bleeding
Cardiogenic shock:
1) Give examples
2) What is its principle pathogenic mechanism?
1) MI, ventricular rupture, arrhythmia, cardiac tamponade, PE
2) Failure of myocardial pump resulting from intrinsic myocardial damage, extrinsic pressure, or obstruction to outflow
Hypovolemic shock:
1) Give examples
2) What is the cause?
1) Hemorrhage, fluid loss (eg, vomiting, diarrhea, burms, trauma)
2) Inadequate fluid volume
Septic shock:
1) Sepsis alters the expression of __________ factors, and it favors ____________.
2) Cytokines (TNF and IL-1) increase what?
3) What initiates the clotting cascade?
1) clotting factors; coagulation
2) Tissue factor production
3) TNF
Septic shock:
1) Give examples
2) Primary pathology mechanisms?
1) Overwhelming microbial infections, gram-negative sepsis, gram-positive septicemia, fungal sepsis, superantigens (e.g. sick syndrome)
2) Peripheral vasodilation and pooling of blood; endothelial activation/ injury; leukocyte-induced damage; DIC; activation of cytokine cascades
Cytokines (TNF and IL-1) increase tissue factor production and TNF initiates the clotting cascade.
1) What 3 things does this inhibit and what does this cause?
2) What does this dampen?
1) Tissue factor pathway inhibitor, thrombomodulin, and protein C; hypercoagulability
2) Fibrinolysis
Septic shock: What diminishes the “washout” of activated coagulation factors in a sepsis scenario? What does this do normally?
Vascular leakage; one of the ways that clotting is regulated in normal physiology
Two primary mechanisms of metabolic derangement in sepsis:
1) Cytokines (TNF and IL-1) upregulate what 4 things? What does this do?
2) What is also occurring at the same time?
1) Stress hormones, glucagon, growth hormone, cortisol; drives gluconeogenesis
2) Inflammatory cytokines suppress insulin release and promote insulin resistance in the liver
What does metabolic derangement in septic shock lead to? Why is this extra bad?
Hyperglycemia; hyperglycemia decreases neutrophil function, so the ability to fight infection is diminished
What happens after the hyperglycemic stage of sepsis if enough time passes?
There can be a respondent adrenal insufficiency and deficit of glucocorticoids
As septic shock and metabolic derangement continues well past the point of hyperglycemia, what is happening to the cells? What chain rxn does this cause?
1) Cells continue bearing the brunt of shock (inadequate perfusion), they become increasingly hypoxic
2) This cause lactic acid to be produced, leading to lactic acidosis
3) Blood pH drops
Septic Shock + organ dysfunction:
1) What 3 things decrease oxygen and nutrients to tissues?
2) What is happening to the mitochondria during this?
3) What happens to the heart during this stage?
1) Systemic hypotension, interstitial edema and small vessel thrombosis
2) Start to take damage bc oxidative stress
3) Myocardial contractility starts to diminish, reducing cardiac output
Septic Shock and organ dysfunction:
1) Towards the end, increased vascular permeability leads to what?
2) What ultimately causes death?
3) Can other types of shock cause this?
1) ARDS
2) Kidneys, liver, lungs, heart are all catastrophically effected
3) Severe shock by other means still leads to poor perfusion which can cause most of this to occur
1) Clinical manifestations of shock depend on what? Explain
2) What does prognosis vary with?
1) Precipitating event; the primary threat to life is the underlying initiating event, though cardiac, cerebral, and pulmonary changes aggravate the situation
2) Origin and duration
Cardiac & Hypovolemic shock: describe how both types tend to present
1) Hypotension
2) Weak pulse
3) Tachypnea
4) Cool, clammy, cyanotic skin
Septic shock: is skin going to be cool or warm? Why?
Skin may be warm and flushed secondary to peripheral vasodilation
List 3 sequalae of shock after the initial period
1) Progressive oligouria
2) Metabolic acidosis
3) Electrolyte imbalances
List the 2 main types of atherosclerosis and where they can occur
1) Generalized: All arteries
2) Localized: Cerebral, Coronary, Aortic
Localized atherosclerosis: list the 3 places it can occur and what can be caused at each
1) Cerebral: stroke
2) Coronary: MI
3) Aortic: Aneurysm rupture
Giant Cell (temporal) arteritis:
1) What is it?
2) Etiology?
1) Granulomatous inflammation with giant cells, lymphocytes, intimal fibrosis
2) Possibly T-cell mediated autoimmune response to vessel wall antigen
What are the 2 main characteristics of giant cell arteritis?
a) Giant cells near fragmented internal elastic membrane
-Formed by fusion of epithelial cells and macrophages
b) Focal destruction of internal elastic membrane
Polyarteritis Nodosa:
1) What is it?
2) Who does it mainly affect? What are 30% of cases associated with?
1) Segmental necrotizing inflammation of small to medium-sized arteries, esp. of kidneys, heart, liver, and Gl tract
2) Young adults; hepatitis B antigen
Polyarteritis nodosa
1) Sx? Chronic, acute, or episodic?
2) What can happen if it is not treated?
3) What happens if treated?
1) Malaise, fever, weight loss; typically episodic
2) Can lead to aneurysms or even rupture
-Fatal in most untreated cases from thromboses and rupture; renal artery is common
3) Remission or cure in 90% with corticosteroids
Thrombangitis Obliterans (Buerger Disease):
1) What vessels does it affect?
2) What is it?
1) Medium and small arteries, mainly of extremities (esp. tibial and radial)
2) Acute and chronic inflammation of the vessel wall, with luminal thrombosis
Thrombangitis Obliterans (Buerger Disease):
1) Who is it almost exclusively found in?
2) What can be curative?
3) What does the thrombus typically contain?
1) Almost exclusively in heavy smokers, usually before 35
2) Cessation
3) Microabscesses
Raynaud Phenomenon:
1) What is it?
2) What does it look like?
3) Prevalence/ demographics?
1) Exaggerated vasoconstriction of digital arteries and arterioles
2) Pallor or cyanosis of fingers and toes
3) 3% to 5%, often in young women
What are the two main causes of Raynaud phenomenon? Describe.
1) Primary: usually benign (hemangiomas)
2) Secondary: caused by other autoimmune disease; maybe first manifestation of those conditions
Familial Hypercholesterolemia:
1) LDL receptor is expressed in the __________ and ___________
2) Hepatic LDL receptors clear half of ____________________ and up to 80% of ___________ from circulation by endocytosis
1) liver and adrenal cortex
2) intermediate-density lipoproteins; LDL
Familial Hypercholesterolemia:
1) Mutations occur through what?
2) Mutations in the LDLR gene disrupt what?
1) Combination of large insertions, deletions and recombination involving Alu repeats
2) Production of LDL receptor and cause accumulation of plasma LDL
Familial Hypercholesterolemia in heterozygotes:
1) ______________ usually manifests at birth and is the only finding in the first decade of life
2) In heterozygotes of all ages, the plasma cholesterol concentration is ______ as high in unaffected individuals
3) In heterozygotes, ____________ and ____________ begin to appear by the end of the second decade
1) hypercholesterolemia
2) twice
3) arcus corneae and tendon xanthomas
The development of coronary artery disease among heterozygotes for familiar hypercholesterolemia depends on what? Explain.
Gender and age (e.g., at age 50, 50% of males have CAD and only 20% of females)
1) Homozygous FH (familiar hypercholesterolemia) presents in the first decade of life with what 2 things?
2) Plasma cholesterol concentration is _______ that of heterozygotes and without aggressive treatment homozygotes will usually die by age ______.
1) Arcus corneae and tendon xanthomas.
2) twice; 30.
What are the 3 main types of shock? What’s wrong with each?
1) Cardiogenic (pump)
2) Hypovolemic (blood volume)
3) Septic (pipes)
