Lecture 4.1 MJ slides

Question 1

List conditions with venous return issue-related edema

Answer 1

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

Question 2

List conditions relating to an oncotic pressure source of edema

Answer 2

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

Question 3

Lymphatic obstruction causing edema; what is it? Give 4 examples

Answer 3

Drain is broken
1) Inflammatory dz
2) Neoplasm: cancer in lymph. system
3) Post surgical: drain is missing
4) Postirradiation: impede flow

Question 4

List conditions involving sodium retention-related edema

Answer 4

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

Question 5

What should you think abt when you hear “sodium”?

Answer 5

Blood volume

Question 6

List types of inflammation that can cause edema

Answer 6

1) Acute inflammation
2) Chronic inflammation

Question 7

What can go wrong with medical clotting inhibition?

Answer 7

1) Factor V Leiden Mutation
2) Protein C and S deficiency
3) Antithrombin III deficiency
4) Von Willebrand’s disease

Question 8

How do we intervene on other pathology with medicines that act on hemostasis? (use an example)

Answer 8

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

Question 9

List 13 conditions that cause hypercoagulability

Answer 9

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)

Question 10

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?

Answer 10

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)

Question 11

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?

Answer 11

1) Immobility + atrial fibrillation (afib)
2) Pregnancy and postpartum + Oral contraceptives (esp. if smoking over 35)
4) Both are sticky

Question 12

Systemic thromboemboli refers to what emboli?

Answer 12

Emboli in circulation

Question 13

1) 80% of arterial thrombi arise from what?
2) Give examples

Answer 13

1) Intracardiac mural thrombi
2) Left ventricular wall infarcts
Dilated left atria secondary to mitral valve defects
Aortic aneurysm
Atherosclerotic plaque

Question 14

1) Arteriolar embolization often causes what?
2) Major sites for venous emboli are ________extremities

Answer 14

1) Tissue infarction
2) lower

Question 15

Fat embolisms
1) Name 2 causes
2) What are the Sx?
3) When is Sx onset and which Sxs come first?

Answer 15

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

Question 16

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?

Answer 16

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

Question 17

Air Embolism:
1) What is it?
2) When is it seen most?

Answer 17

1) Gas bubble coalesce to form occlusion that can cause ischemic injury
2) Mostly from surgical procedures like laproscopy

Question 18

Factor V Leiden:
1) What is its inheritance?
2) What exacerbates it?
3) What is the demographic?

Answer 18

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

Question 19

Factor V Leiden: what are 2 signs on physical exam?

Answer 19

1) DVT
2) Possible PE

Question 20

1) What factor accelerates clotting?
2) What is the inheritance risk of Factor V Leiden if one parent carries a mutant allele?

Answer 20

1) Factor V accelerates clotting
2) 50% risk of child getting it with 10% penetrance, so a 5% lifetime risk

Question 21

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?

Answer 21

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!

Question 22

Why is PT/INR PTT always required for baseline before starting heparin?

Answer 22

Heparin induced thrombocytopenia (HIT)

Question 23

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?

Answer 23

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

Question 24

Cardiogenic shock:
1) Give examples
2) What is its principle pathogenic mechanism?

Answer 24

1) MI, ventricular rupture, arrhythmia, cardiac tamponade, PE
2) Failure of myocardial pump resulting from intrinsic myocardial damage, extrinsic pressure, or obstruction to outflow

Question 25

Hypovolemic shock: 1) Give examples 2) What is the cause?

Answer 25

1) Hemorrhage, fluid loss (eg, vomiting, diarrhea, burms, trauma) 2) **Inadequate fluid volume**

Question 26

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?

Answer 26

1) clotting factors; **coagulation** 2) Tissue factor production 3) TNF

Question 27

Septic shock: 1) Give examples 2) Primary pathology mechanisms?

Answer 27

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

Question 28

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?

Answer 28

1) Tissue factor pathway inhibitor, thrombomodulin, and protein C; hypercoagulability 2) Fibrinolysis

Question 29

Septic shock: What diminishes the “washout” of activated coagulation factors in a sepsis scenario? What does this do normally?

Answer 29

Vascular leakage; one of the ways that clotting is regulated in normal physiology

Question 30

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?

Answer 30

1) Stress hormones, glucagon, growth hormone, cortisol; drives gluconeogenesis 2) Inflammatory cytokines suppress insulin release and promote insulin resistance in the liver

Question 31

What does metabolic derangement in septic shock lead to? Why is this extra bad?

Answer 31

Hyperglycemia; hyperglycemia decreases neutrophil function, so the ability to fight infection is diminished

Question 32

What happens after the hyperglycemic stage of sepsis if enough time passes?

Answer 32

There can be a respondent adrenal insufficiency and *deficit* of glucocorticoids

Question 33

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?

Answer 33

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

Question 34

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?

Answer 34

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

Question 35

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?

Answer 35

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

Question 36

1) Clinical manifestations of shock depend on what? Explain 2) What does prognosis vary with?

Answer 36

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

Question 37

Cardiac & Hypovolemic shock: describe how both types tend to present

Answer 37

1) Hypotension 2) Weak pulse 3) Tachypnea 4) Cool, clammy, cyanotic skin

Question 38

Septic shock: is skin going to be cool or warm? Why?

Answer 38

Skin may be warm and flushed secondary to peripheral vasodilation

Question 39

List 3 sequalae of shock after the initial period

Answer 39

1) Progressive oligouria 2) Metabolic acidosis 3) Electrolyte imbalances

Question 40

List the 2 main types of atherosclerosis and where they can occur

Answer 40

1) Generalized: All arteries 2) Localized: Cerebral, Coronary, Aortic

Question 41

Localized atherosclerosis: list the 3 places it can occur and what can be caused at each

Answer 41

1) Cerebral: stroke 2) Coronary: MI 3) Aortic: Aneurysm rupture

Question 42

Giant Cell (temporal) arteritis: 1) What is it? 2) Etiology?

Answer 42

1) Granulomatous inflammation with giant cells, lymphocytes, intimal fibrosis 2) Possibly T-cell mediated autoimmune response to vessel wall antigen

Question 43

What are the 2 main characteristics of giant cell arteritis?

Answer 43

a) Giant cells near fragmented internal elastic membrane -Formed by fusion of epithelial cells and macrophages b) Focal destruction of internal elastic membrane

Question 44

Polyarteritis Nodosa: 1) What is it? 2) Who does it mainly affect? What are 30% of cases associated with?

Answer 44

1) Segmental necrotizing inflammation of small to medium-sized arteries, esp. of kidneys, heart, liver, and Gl tract 2) Young adults; hepatitis B antigen

Question 45

Polyarteritis nodosa 1) Sx? Chronic, acute, or episodic? 2) What can happen if it is not treated? 3) What happens if treated?

Answer 45

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

Question 46

Thrombangitis Obliterans (Buerger Disease): 1) What vessels does it affect? 2) What is it?

Answer 46

1) **Medium and small arteries**, mainly of extremities (esp. **tibial and radial**) 2) Acute and chronic inflammation of the vessel wall, with luminal thrombosis

Question 47

Thrombangitis Obliterans (Buerger Disease): 1) Who is it almost exclusively found in? 2) What can be curative? 3) What does the thrombus typically contain?

Answer 47

1) Almost exclusively in heavy smokers, usually before 35 2) Cessation 3) Microabscesses

Question 48

Raynaud Phenomenon: 1) What is it? 2) What does it look like? 3) Prevalence/ demographics?

Answer 48

1) Exaggerated vasoconstriction of digital arteries and arterioles 2) Pallor or cyanosis of fingers and toes 3) 3% to 5%, often in young women

Question 49

What are the two main causes of Raynaud phenomenon? Describe.

Answer 49

1) **Primary:** usually benign (hemangiomas) 2) **Secondary:** caused by other autoimmune disease; maybe first manifestation of those conditions

Question 50

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

Answer 50

1) liver and adrenal cortex 2) intermediate-density lipoproteins; LDL

Question 51

Familial Hypercholesterolemia: 1) Mutations occur through what? 2) Mutations in the LDLR gene disrupt what?

Answer 51

1) Combination of large insertions, deletions and recombination involving Alu repeats 2) Production of LDL receptor and cause accumulation of plasma LDL

Question 52

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

Answer 52

1) hypercholesterolemia 2) twice 3) arcus corneae and tendon xanthomas

Question 53

The development of coronary artery disease among heterozygotes for familiar hypercholesterolemia depends on what? Explain.

Answer 53

Gender and age (e.g., at age 50, 50% of males have CAD and only 20% of females)

Question 54

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 ______.

Answer 54

1) Arcus corneae and tendon xanthomas. 2) twice; 30.

Question 55

What are the 3 main types of shock? What's wrong with each?

Answer 55

1) Cardiogenic (pump) 2) Hypovolemic (blood volume) 3) Septic (pipes)