Hemodynamics and Autoimmune Diseases Flashcards Preview

Block 2 Pathology > Hemodynamics and Autoimmune Diseases > Flashcards

Flashcards in Hemodynamics and Autoimmune Diseases Deck (268):
1

What is decreased plasma osmotic pressure? Describe a clinical example.

- Pressure exerted by proteins, notably albumin, in blood vessel’s plasma that tends to pull water into circulatory system

- Albumin: accounts for nearly 50% of total plasma protein and is major protein maintaining plasma osmotic pressure

- Nephrotic syndrome –> edema from decreased plasma oncotic pressure due to protein loss through kidneys

 

1

What is hemorrhage? Describe 5 subcategories.

- Hemorrhage: extravasation of blood due to blood vessel rupture; common, commonly serious, and described with large number of precise terms (continuum of trivial to fatal)

- Hematoma: hemorrhage enclosed in tissue

- Hemothorax: hemorrhage into pleural cavity

- Hemopericardium: hemorrhage into pericardial space

- Hemoperitoneum: hemorrhage into abdominal cavity

- Hemarthrosis: hemorrhage into a joint (commonly associated with hemophilia) 

1

What is Glanzmann thrombasthenia? Describe 2 drugs that use a similar mechanism in a beneficial way.

- Rare deficiency of platelet Gp2b3a receptors causes bleeding tendency due to deficient platelet aggregation

- Some snake venom contains substances that bind to platelet Gp2b3a receptors, mimicking this disease

- Eptifibatide (Integrilin): similar mechanism to the snake venom; given IV to pts who are clotting off coronary arteries

- Clopidogrel (Plavix): blocks platelet ADP receptors (preventing conformational change that mediates binding of Gp2b3a to fibrinogen, and aggregation) –> taken orally by pts who have suffered clotting of critical coronary or cerebral arteries 

1

How might shock cause pulmonary alveolar edema? What is the most common cause of this type of edema?

- Shock (total body ischemia) causes acute lung injury (ALI)

- ALI causes increased vascular permeability, in turn causing alveolar edema

- However, this is NOT the most common cause of pulmonary alveolar edema -> increased hydrostatic pressure from left heart failure is

1. Blood gets backed up due to increased pressure, which, when it gets too high, loosens the junctions b/t pulmonary alveolar capillary endothelial cells, and leaks into the airspaces

1

What is this? Why are there dimples in the skin?

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- Peau d'orange: lymphedema due to breast cancer causing the skin over the tumor to resemble the skin of an orange 

- Cooper's suspensory ligaments are pulling back on the skin

1

How does stasis promote thrombosis?

- Allows platelets to spend more time sitting on endothelial cells (vs. normal blood flow, where platelets concentrated in center of vessel, with plasma toward outside)

- Any factor slowing blood flow makes intravascular clot formation more likely

 

1

How does cancer cause HS?

- Inflammatory response to malignant tumors and necrotic debris they release into general circulation when they outgrow their blood supply

- Also compress or invade veins, obstructing blood flow, and creating turbulent flow or stasis

- Mucin: high molecular weight, heavily glycosylated thrombogenic proteins produced by malignant glandular tumors

- Migratory thrombophlebitis: simultaneous VT and inflammation at multiple sites due to malignant tumors, aka Trousseau syndrome

Note: CANCER IS A FREQUENT CAUSE OF HYPERCOAGULABILITY BECAUSE IT SIMULTANEOUSLY INDUCES INFLAMMATION AND CLOTTING, BUT ALSO BECAUSE IT IS COMMON ITSELF

1

What is antiphospholipid antibody syndrome?

- Rare, life-threatening acquired HS that causes arterial thrombosis

- Common in young females

- Autoantibodies against phospholipids (plasma protein antigens unveiled by binding phospholipids) –> may be in association with lupus erythematosus

- Present with recurrent miscarriages, DVT in legs, cerebral infarctions, migraine headaches, cardiac vegetations, ischemic hands/feet, thrombocytopenia, and others

- Abs present in 1-5% of asymptomatic individuals, suggesting syndrome requires more than just their presence 

1

What is the difference between medium-sized and large-sized PE?

- Medium sized -> can cause hemorrhagic infarction (if bronchial arterial blood supply impaired), leading to hemoptysis (uncommon)

- Large size –> acute cor pulmonale (leading to right heart failure) and sudden death (must block >60% or more of pulmonary circulation to have this effect 

1

What is PTPN22?

- PTPN22 is a tyrosine phosphatase gene

- Polymorphisms in this gene are associated with rheumatoid arthritis and type 1 diabetes mellitus, among other autoimmune diseases

1

What are the gross and microscopic pathology, symptoms, and signs of Sjogren syndrome?

- Gross: dry ocular and oral mucosa, enlarged salivary and lacrimal glands

- Microscopic: 1) intense infiltration of CD4 T cells, 2) destruction of gland architecture, +/- plasma cells, +/- germinal centers. Renal involvement: interstitial nephritis rather than glomerulonephritis.

- Symptoms: dry eyes, dry mouth

- Signs: dry mucous membranes of eyes and mouth, conjunctival ulcers, oral ulcers, enlarged salivary and lacrimal glands

 

IMPORTANT CONCEPT: Symptoms of dry eyes and dry mouth suggest the possibility of Sjogren syndrome

1

How are kidney transplant biopsies evaluated for evidence of BK virus infection?

- Aka, polyomavirus nephropathy

- Can be manifested by intranuclear inclusion bodies and epi cell injury and lysis. Immunostains used to confirm sighting of BK virus inclusions. Urine also checked for BK virus by “BK virus activation assays,” including quantitative PCR assays, urine cytology and/or urine electron microscopy, but positive urine assays must be correlated with plasma assays b/c clinically significant urine assays associated with simultaneously positive plasma assays

3

What is the consensus definition of sepsis?

SIRS due to infection, proven or highly suspected, meeting at least 2 of these 4 criteria:

1. Fever >38 or hypothermia

2. P >90/min

3. Tachypnea >20/min or hyperventilation (arterial pCO2

4. Leukocytosis (WBC > 12,000/cu mm), leukopenia (WBC 10%)

NOTE: sepsis and SIRS are on a continuum, and the criteria for the subsets are arbitrary -> the consensus definitions of sepsis and SIRS have always been problematic, and do not work for small children (high resting HR and WBC), for example -> IN DISEASE DX, THERE IS NO SUBSTITUTE FOR EXPERIENCE

4

What is primary hemostasis, and what are its mediators?

- Platelet adhesion to thrombogenic ECM

- Platelet adhesion to ECM mediated by von Willebrand factor, which binds to Gp1b receptors on platelets –> change in shape from smooth-surfaced discs to spheres with long, spiky projections

- Change in shape associated with conformational change in Gp2b3a receptors, making them bind fibrinogen, which then binds to altered receptors on adjacent platelets, linking them in aggregate

- All of this is associated with release of ADP and thromboxane A2 (a COX derivative) from platelet granules, causing additional platelet recruitment and aggregation, resulting in primary hemostatic plug 

4

What are the two "stages" of acute kidney injury (AKI)?

1. Earliest finding: tubular epithelial edema 

2. Later, worse injury: acute tubular necrosis, but tubular epithelial cells can regenerate and be replaced (glomeruli cannot, but are not typically affected in shock)

4

What is the nature of the fluid on the cut surface of this lung in a patient who died of shock?

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- This is alveolar edema fluid, which is typically white and bubbly 

- Pulmonary alveolar edema is the typical manifestation of acute lung injury (ALI) in the early phase (first day)

1. Note: ALI has many causes, not just shock

5

What 5 things must you describe of any infarct, hemorrhage, tumor, or lesion?

1. Size
2. Shape
3. Color
4. Consistency, including texture (this is the only one that requires more than seeing, i.e., palpation)
5. Relationships (including location and proximity to other things) 

6

Describe the relationship between heart failure and kidney function.

Heart failure reduces renal blood flow, activating renin-angiotensin-aldosterone system, and causing retention of Na and H2O –> 2 simultaneous types of edema (Na retention and increased hydrostatic pressure

7

What is Bernard-Soulier syndrome?

Rare deficiency of platelet Gp1b receptors for von Willebrand factor causes bleeding tendency 

7

A 45-year-old obese black female mother of three comes to the emergency department with constant severe epigastric abdominal pain radiating to her back, associated with nausea and vomiting.  Her temperature is 39 degrees C (102.2 degrees F), pulse 130/minute, blood pressure 100/60 mm Hg and respirations 25/minute.  She sits on the gurney with her knees to her chest.  Her abdomen is tender in the right upper quadrant.  Her skin is warm.

Shock due to SIRS due to acute pancreatitis due to gallstone obstruction of pancreatic duct

7

Why is treatment of DIC so complex?

NATURAL HX OF DIC IS EVOLUTION TO CONSUMPTIVE COAGULOPATHY FOR WHICH TX IS THE OPPOSITE, MAKING THIS A VERY DIFFICULT CONDITION TO MANAGE 

7

What are the four fates of a thrombus?

1. Dissolution: dissolving by fibrinolysis (endogenous or exogenous)

2. Propagation 

3. Embolization 

4. Organization (and recanalization): can occur in pneumonias, exudates, injuries, etc., and not just thrombus

 

 

7

What are anergic lymphocytes?

Functionally unresponsive

7

What are the definition, epidemiology, and pathogenesis of systemic lupus erythematosus?

- Definition: prototype multisystem autoimmune disease

- Epi: “fairly common" -> up to 13X more common in women, more common in blacks, affects 1 in 245 black women, most common in child-bearing age (15-45), more severe in blacks and Asians

- Pathogenesis: failure of self-tolerance, antinuclear antibodies, genetic factors, environmental factors (meds, UV light, sex hormones), immunologic factors (activation of helper T cells and B cells, IgG autoAb production, immune complexes)

8

What is Prothrombin G20210A mutation?

- Leads to elevated prothrombin levels and an almost 3-fold increased risk of VT 

- Single mutation in 3' untranslated region of prothrombin gene (1-2% of population) associated with hypercoagulability

9

What is this?

Q image thumb

- Passive congestion: caused by right heart failure due to backup of blood inadequately pumped out of heart; associated with gross pathological finding of nutmeg liver

- Hemorrhagic necrosis spanning multiple lobules alternating with steatotic areas (can be acute or chronic) 

9

What is going on here? What is the most likely pathophysological mechanism of this condition?

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- Lung tissue: abnormal, lots of RBCs, congested capillaries, no air exchange possible b/c airspaces filled w/pink proteinaceous fluid -> pulmonary alveolar edema 

- Most common cause is: left heart failure (congestive heart failure) 

- Increased hydrostatic pressure is the most likely mechanism

 

9

What is this and what is the most common cause?

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- Nutmeg liver: passive congestion of the liver 

- Right heart failure is the most common cause (the most common cause of right heart failure is... left heart failure)

9

What are the 4 fates of a thrombus?

1. Dissolution: complete or partial removal of the clot by fibrinolysis 

2. Propagation: growth of the clot 

3. Embolization: travel of a detached, intravascular solid, liquid, or gaseous mass from its point of origin in the vascular system to a distant site (this is not likely to be the way a large thrombus would evolve)

4. Organization (and re-canalization -> may lead to partial, or no, reopening of the channel; you could call this a scar)

NOTE: these are NOT mutually exclusive

9

Why is it important to monitor how long you leave in venous catheters (that you put in, and others put in pts you are responsible for)?

- Thrombi being propagated every day you leave a catheter in place, and these can become infected -> infection, embolization, and o/complications of peri-catheter thrombi kill pts every day 

 

- EXTRA: used to be guideline to change every 5 days, but intensivists pushed back because there are only so many sites to put these in –> there is an active discussion about whether these should stay in every day (typically on a blood thinner too if not contraindicated and need this for a long time; also long-term catheters designed specifically for this)

9

What are the 3 TNF-alpha blockers?

1. Infliximab (trade name Remicade)

2. Etanercept (trade name Enbrel)

3. Adalimumab (trade name Humira) 

9

How do you diagnose and treat systemic sclerosis?

Diagnosis: generalized cutaneous sclerosis, HTN, renal failure, pulmonary HTN and fibrosis. Supported by serology: Anti-DNA topoisomerase I (anti-Scl70) in 28-70% of diffuse SS pts. Anticentromere Ab in 22-36% of limited SS pts

- Treatment: Non-pharmacologic: exercise, splinting, avoid cold. Pharmaco: immunomodulators, antifibrotics, cyclophosphamide, methotrexate, glucocorticoids. Hematopoietic stem cell transplant (HSCT): yields clinical response in 67%, but high risk of mortality (10%)

10

Describe the vasoconstriction stage of hemostasis. What are its two mediators?

- Brief arteriolar vasoconstriction mediated by:

1. Reflex neurogenic mechanisms, augmented by

2. Local secretion of vasoconstrictors like endothelin, a potent endothelium-derived vasoconstrictor 

11

What are the 5 physiological categories of edema?

1. Increased hydrostatic pressure

2. Decreased plasma osmotic pressure 

3. Sodium retention 

4. Inflammation 

5. Lymphatic obstruction 

12

BONUS QUESTION: What do you think might be going on with this lung?

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Terrible pulmonary emphysema and aspergillosis (fungal infection)

12

What is post-transplant lymphoproliferative disorder?

- Spectrum ranging from proliferation of lymphocytes that halts w/decreasing immunosuppressive therapy to full-blown malignant lymphoma that can be resistant to chemotherapy and everything in between

- Proliferating lymphocytes are infected with EBV in most cases, and immunosuppression can awaken latent EBV, driving lymphoproliferation that may be partly controllable

- In situ hybridization can be performed to detect the EBV in PTLD -> these lymphocytes must be differentiated from those carrying out immunological attack on transplanted organ or an immunological defense against infection

- All organ transplant biopsies must be evaluated for PTLD

12

Are different types of organ transplant evaluated in the same way?

No -> there are separate schemes for evaluating lung transplant, heart transplant, liver transplant, pancreas transplant, intestinal transplant and other sorts of transplant biopsies for rejection

- This is because transplant rejection takes different forms in different tissues

13

What is the best way to treat shock?

To treat the inciting event, and the best way to do that is to categorize it

13

What is the relationship between vital signs and shock?

- Vital signs are late responders to shock, so there is considerable tissue injury by time P>100 and BP

- Characteristic of young people with shock to compensate better and longer than old people –> tend to experience a rapid, and irretrievable crash

 

13

List some cytokines commonly produced by PAMP interaction with host cell receptors.

PAMPs activate inflammatory cells, producing cytokines (IC messengers secreted by innate/acquired immune system that tell other cells what to do, but do not travel too far, b/c then they would be hormones):

1. TNF
2. IL-1, IL-8: cause mast cells in CT adjacent to blood vessels to release large quantities of histamine from cytoplasmic granules (also released from platelets), causing dilation of arterioles and increased permeability of venules
3. IL-6, IL-12, IL-18
4. INF-gamma: activates phagocytic killing of IC bacteria, and makes T-cells upregulate CD40L, which binds CD40 on APCs, which release IL-12 and sustain expression of costimulatory molecules, including CD80 (B7), which binds CD28, resulting in T cell activation and proliferation
5. High mobility group box 1 protein (HMGB1) 

14

A 25-year-old white male soldier on leave comes to the emergency department with headache, fever, malaise, nasal congestion, and a sore throat.  His temperature is 39 degrees C (102.2 degrees F), pulse 140/minute, blood pressure 80/30 mm Hg and respirations 30/minute.  He is confused.  His neck is stiff.  His skin is warm, with numerous petechiae and purpura

Septic shock due to Waterhouse-Friderichsen syndrome due to meningococcal meningitis 

14

What is the microscopic pathology of systemic lupus erythematosus?

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- Acute necrotizing vasculitis of small arteries and arterioles (with fibrinoid deposits), nephritis in 50% (5 patterns of glomerulonephritis: minimal, mesangial, focal proliferative, diffuse proliferative and membranous, [glomerular granular deposits of IgG and complement, subendothelial dense deposits causing wire loop lesions, most common in diffuse proliferative & indicative of active disease]), cerebritis in 50%

15

What is the relationship between catheters and clots?

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- A clot forms around every catheter you put in -> danger of embolization and infection of the clot 

- This image shows fixed segments of SVC thrombi around a catheter (removed)

16

Why does this activity lead to a hypercoagulable state, and sometimes thrombus?

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- Sx inevitably spills activated clotting factors and platelets into circulation b/c they are not all perfectly used up at the sx site

- Activated clotting factors and platelets in circulation may cause thrombosis of arteries and veins in the heart, brain, or limbs far from the sx site 

- SX ALWAYS CAUSES A HYPERCOAGULABLE STATE

17

What Ab test is associated with polymyositis/dermatomyositis?

Anti-Jo-1 (one type of anti-synthetase)

17

What is mycophenolate mofetil?

- Trade name is CellCept

- Reversible inhibitor of inosine monophosphate dehydrogenase in purine biosynthesis (specifically guanine synthesis) that inhibits DNA replication, which inhibits lymphocyte proliferation

- Used in treating autoimmune diseases, particularly systemic lupus erythematosus, and in preventing and treating transplant rejection

18

What is this?

Q image thumb

- Hyperemia due to photo sensitivity 

- Note the red color 

- Arterial

20

What is mucin?

High molecular weight, heavily glycosylated thrombogenic proteins produced by malignant glandular tumors

 

21

How do pro-inflammatory cytokines affect leukocytes?

Upregulate expression of endo cell adhesion molecules that bind leukocytes, directing them to site of infection 

22

What are Pembrolizumab and Nivolumab?

- Immunotherapies consisting of antibodies to PD-1

- Effective and were FDA approved for treating metastatic melanoma in 2014

23

What is this?

Q image thumb

Thrombus with lines of Zahn

23

What is Ipilimumab?

- Antibodies to CTLA-4 that "block the blockers," unblocking the immune response 

- Have proven effective in treatment of some tumors, e.g., approved by FDA for tx of melanoma in 2011 

24

What are the thrombus and antithrombotic events in hemostasis?

- Solid, semi-permanent plug of aggregated platelets and polymerized fibrin

- Counter-regulatory mechanisms limit plug to site of injury (expression of thrombomodulin on endothelial cell surface)

- Thrombomodulin binds thrombin, together activating protein C

- Fibrinolytic system: critical for breaking down thrombi, and Includes tissue plasminogen activator (t-PA), plasmin, tissue factor pathway inhibitor, antithrombin III, heparin-like molecules, protein S, and urokinase

24

What is going on here?

Q image thumb

- Marantic endocarditis (3 vegetations) 

- This is the left ventricle, mitral (bicuspid) valve; thick walls are a clue

24

What is the difference b/t white and red infarcts?

- White anemic: infarcts typical of solid organs with end-arterial circulation (heart, spleen, kidney) 

- Red hemorrhagic: infarcts typical with venous occlusion (e.g., ovarian torsion), or dual or anastomosing blood supply (e.g., lung, intestine) reperfusion

24

What is Tocilizumab?

New antibody that blocks IL-6 receptors

25

What is this?

Q image thumb

- Congestion: passive decrease in venous blood flow 

- Due to SVC backup (obstruction) in this case 

- Note the blue color 

- Venous

 

NOTE: normal hemoglobin: 15 mg/dl –> has to get down to about 5 for blood to start looking blue (regardless of what the starting level was; e.g., in cyanosis) 

26

What is thrombosis?

- Inappropriate formation of blood clot in a blood vessel, usually occlusive 

- THROMBOSIS IS COMMON AND SERIOUS, MORE COMMON IN VEINS AND MORE SERIOUS IN ARTERIES 

28

What is programmed-death 1?

- PD-1: anti-stimulatory molecule 

- Some tumors (cells proliferating out of control) and virally infected cells use PD-1 to block the immune response that would kill them off

- Immunotherapies consisting of antibodies to PD-1 (pembrolizumab and nivolumab) are effective and were FDA approved for treating metastatic melanoma in 2014

30

What are the 3 most common types of shock?

- Septic, cardiogenic, and hypovolemic 

- Nearly as important as recognizing shock is accurately categorizing b/c this determines treatment


 

31

What is this 2cm lesion?

Q image thumb

Pulmonary hemorrhagic infarct: lungs have dual blood supply (85% from pulmonary aa and 15% from bronchial aa), so characteristically red hemorrhagic infarcts 

1. 15% from bronchial aa usually not enough to sustain segment of pulmonary parenchyma deprived of pulmonary arterial blood by embolus, but is enough to pour blood into infarcted parenchyma once aa break down 

- Most infarcts wedge-shaped, with occluded artery at apex, and periphery of organ forming base 

- Young people more likely to have hemorrhagic pulmonary infarcts b/c older people have more atherosclerosis, and are not as likely to have good dual blood supply

32

Name 6 primary hypercoagulable states.

- Factor V Leiden mutation

- Prothrombin gene mutation

- Methyl-tetra-hydro-folate reductase gene mutation

- Anti-thrombin 3 deficiency

- Protein C deficiency

- Protein S deficiency

Note: PATIENTS UNDER AGE 50, WHO PRESENT WITH THROMBOSIS, SHOULD BE WORKED UP FOR INHERITED HYPERCOAGULABILITY 

33

A patient taking dabigatran (direct thrombin inhibitor) presents with upper abdominal pain. The most likely cause is gastric hemorrhage due to inhibition of...?

Stage 3 hemostasis

34

What are in the white matter of this brain?

Q image thumb

Petechiae (abnormal)

35

What is coagulative necrosis?

 

- Most common histologic form of infarct –> usually apparent after 12-18 hours, and usually elicits inflammatory response

- Neutrophilic response peaks at 1-2 days, and is followed by macros and fibroblasts

- Liquefactive in brain; necrotizing infection can cause abscess 

36

What are the collections of tiny, red dots on this organ?

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Petechiae, which are small hemorrhages, (and ulcer) on mucosa of the stomach

37

What organ/feature are we looking at? What are the dark pink things featured in the middle of the slide?

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- Renal glomerulus 

- Fibrin thrombi/thromboemboli (blood clots) associated with disseminated intravascular coagulation (DIC) 

- Waterhouse Friderichsen Syndrome 

37

What is the threshold loss of blood volume for shock?

- Loss of about 25-30% (old – young) of person’s blood volume is threshold for shock

- 15-20% loss = symptoms and signs of compensation

- 10% loss = blood donation

- 35-45% life-threatening, but survivable if dx and treated quickly

- 50% CONSIDERED DIVIDING LINE B/T LETHAL AND NON-LETHAL

Note: depends on how slowly this takes place, and health of the person (i.e., someone with infarction of heart muscle and narrowed arteries may die of 5% blood loss)

39

What is shock, and some of its common signs?

- A state of systemic (total body) hypoperfusion and CV collapse 

- Not defined by particular BP b/c not a #, but rather a syndrome: constellation of signs and symptoms of total body hypoperfusion

- Important variations depending on type, but always affects pt. as a whole person

- Signs (beginning with earliest) –> agitation (non-specific), decreasing mental status, confusion, lethargy, delirium, and coma 

40

What is the most common manifestation of chronic cor pulmonale? Acute?

- Right ventricular hypertrophy: this is where most of the compensatory pumping is happening to combat the high pulmonary pressure ->pure hypertrophy if totally able to compensate, but there may be some dilation if right ventricle unable to compensate appropriately 

- Acute: right ventricular dilation 

41

What is amniotic fluid embolism?

- Can be caused by tears in placental membranes during course of L&D

- Breaks can cause squamous cells, lanugo hair, vernix caseosa fat, and mucin in pulmonary microcirculation

- Sudden syndrome of severe dyspnea, cyanosis, and shock during L&D can be due to amniotic embolism, but rare –> PE more common cause

- Fetal cells and fragments of placenta in maternal circulation all the time in pregnancy, but difference in pts. w/embolism vs. those w/o is mom’s immune reaction to bolus (single, large amount) during L&D –> similar rxn to SIRS or anaphylaxis or septic shock, suggesting it is caused by similar cytokine storm of pro-inflammatory mediator release and pro-coagulant activation  

42

What 2 antibody tests are associated with systemic sclerosis?

1. Anti-Scl70 (anti-DNA topoisomerase); diffuse systemic sclerosis

2. Anti-RNA polymerase (anti-U3 RNP)

3. Anti-centromere (limited use for systemic sclerosis)

43

How can infections trigger autoimmune diseases?

- Infections can upregulate co-stimulatory molecules on APCs in nonspecific way

- If self-antigens among those presented w/these co-stimulators, autoimmunity may result 

44

What are these?

Q image thumb

- Petechia: tiny (1-2mm) hemorrhages due to platelet deficiency (abnormal NUMBER or FUNCTION)

45

What is shock lung?

- A form of acute lung injury (ALI), formerly called diffuse alveolar damage (DAD) 

- Correlated with Acute Respiratory Distress Syndrome (ARDS)

46

What is this?

Q image thumb

- Colonic infarct (red): ischemic bowel with necrosis and hemorrhagic infarct (dusky bowel)

48

Describe inflammatory edema, and the different types of fluid accumulated (localized vs. generalized).

- Localized (infection site) or generalized (SIRS or sepsis)

- Exudate at site of inflammation (chemokines)

- Transudate away from site of initiating event

49

What is the most common type of hypovolemic shock? Which of these are the most difficult to catch?

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- Hemorrhagic shock

- Most pts. with hypovolemic shock have bleeding, dhiarrea, vomiting, or dehydration obvious from the history and physical, but not all...

- The trickiest will be retroperitoneal b/c there are not pain endings there 

1. Another challenge is bleeding into the GI tract (i.e., from a peptic ulcer) -> shock may be the only sign

50

What are the 3 types of thrombi?

1. Arterial: rich in platelets (white thrombi)

2. Venous: rich in erythrocytes (red thrombi); clinically most important in legs, arms, pelvis

3. Mural: on wall of heart

 

51

A 25-year-old black female school teacher with no history of smoking or ethanol use comes to the emergency department with fever, chills, malaise and a cough.  Her temperature is 39 degrees F (102.2 degrees F), pulse 140/minute, blood pressure 90/50 mm Hg and respirations 30/minute.  She is confused.  She has pulmonary crackles over the right lower lobe lung field.  Her skin is warm. What is this a classic clinical scenario for?

Septic shock due to bacterial pneumonia

52

What are the 4 stages of hemostasis at the site of vascular injury?

1. Vasoconstriction 

2. Primary hemostasis 

3. Secondary hemostasis

4. Thrombus and antithrombotic events 

53

What are these?

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Ecchymosis: larger (over 1cm) subcutaneous hemorrhage that goes from red-blue, to blue-green, to gold-brown as the hemoglobin breaks down (name usually used just for skin or oral cavity)

55

What are platelets? List all of their homeostatic (6) and healing (4) contents.

- Cellular components of blood, anucleate pieces of megakaryocyte cytoplasm important in initiation/propagation of clotting

- Contain ADP, fibrinogen, clotting factors V and VIII, Ca, and epinephrine (all important in homeostasis)

- Also contain TGF-beta, PDGF, platelet factor-4 (a heparin-binding chemokine), and fibronectin (all play roles in healing)

56

What does friable mean?

Will break apart (like crumbly cheese)

57

What are purpura?

Medium (3-10mm) bleeds due to vasculitis, vessel fragility, etc. 

57

What are paradoxical emboli?

- Pass through patent foramen ovale or atrial septal defect and go to organs besides the lungs 

1. Called paradoxical b/c you'd suspect these would get caught in the small capillaries and vessels in the lungs -> instead, bypass these via the two underlined irregularities denoted above 

58

What is hydroxychloroquine?

- Trade name Plaquenil

- Anti-malarial antibiotic that happens to have anti-inflammatory activity, and is used in treating systemic lupus erythematosus and RA

- Reputation for low toxicity.  

59

What are the definition and epidemiology of systemic sclerosis?

- Definition: chronic disease w/abnormal accumulation of fibrous tissue in skin and other organs

1. Diffuse: widespread skin, early visceral involvement

2. Limited: skin of fingers/forearms/face and late visceral involvement. Often in context of CREST syndrome

- Epi: Incidence: 10-20 cases/million/year. Prevalence: 4-253 cases/million. Female predominance (F:M = 3:1).  Highest incidence in 50-60 year-olds. Most severe in African Americans, especially women.

61

What is (was) going on here?

Q image thumb

- Hemoperitoneum: bleeding into abdominal and pelvic cavity (due to misdirected femoral catheter, in this case)

- Hemorrhage: extravasation of blood due to blood vessel rupture 

61

A 25-year-old East Asian female medical student comes to the emergency department with headache, fever, malaise, myalgias, nasal congestion and a sore throat.  Her temperature is 39 degrees C (102.2 degrees F), pulse 140/minute, blood pressure 80/30 mm Hg and respirations 30/minute.  She is confused.  She has bilateral pulmonary crackles.  Her skin is warm and flushed. What is this a classic clinical scenario for?

Septic shock due to influenza

62

What is hypovolemic shock?

- Can be due to bleeding or fluid loss from vomiting, diarrhea, or extensive burns

- WEAK, RAPID (thready) PULSE, and COOL, CLAMMY (sweaty), sometimes CYANOTIC SKIN

- TX: blood transfusion

- Most common of the 3 types (at least in sx and trauma pts.)

- Bleeding sufficiently severe to cause shock can be occult, esp. when in the retroperitoneum, abdominal cavity, chest cavities, or intestines 

63

What is cytotoxic T-lymphocyte-associated protein 4?

- CTLA-4: binds to B7 molecules on APCs more strongly than CD28, inhibiting T-cell activation 

1. REMEMBER: T-cells must recognize MHC on APCs and receive costimulation from B7 (via CD28) to be activated, or they will become anergic 

- Some malignant neoplasms use CTLA-4 to evade destruction by T-cells

- Polymorphisms in CTLA-4 gene are associated with some autoimmune endocrine diseases 

64

What are thrombi?

- Blood clots in blood vessels

- Frequently have layering (forming in stages) –> some layers rich in platelets and others rich in erythrocytes –> Lines of Zahn

65

What is congestion?

- Passive decrease in venous outflow, causing cyanosis (abnormal bluish coloration due to presence of excess deoxygenated blood in tissue)

- Cyanosis due to CV or pulmonary disease tends to be first visible around lips (or nailbeds)

- Both hyperemia and congestion are common, but not serious (abnormally large amount of blood where it belongs)

66

Imagine someone just pressed down on this leg with their finger- what is this? What causes it?

Q image thumb

- Pitting edema: transient pit in the skin at the site of finger pressure (pit stays there for awhile when you take your finger away) 

- Caused by fluid in the interstitial space 

66

What is the strongest known genetic predisposition to autoimmune disease?

- Ankylosing spondylitis from HLA B27 allele

- Ankylosing spondylitis: destroys the articular cartilage of the sacroiliac joints and apophyseal joints between spinal tuberosities and processes, resulting in bony fusion across the joints, presenting as lower back pain and spinal stiffness in middle age

B27 allele confers 100-200x risk of getting ankylosing spondylitis and 90% of patients with the disease have the B27 allele

1. Vast majority of people with B27 allele never develop ankylosing spondylitis, and this is NOT a severe or life-threatening disease

67

Central venous catheters have many uses, and are increasingy prevalent in the US. This pt. had two catheters in the SVC, shown here, one going all the way through the right heart into the pulmonary artery. If the pt. had lived, and these catheters were not removed, this condition would most likely have evolved primarily by which of the 4 fates of a thrombus?

- Propagation: gradually obliterating the lumen (also a real candidate for embolization -> risk of this when you pull this catheter out too) 

- NOT dissolution (abnormal flow: slow lysis), embolization (too big for that to be primary), hemostasis (that's good thrombus, not this), organization (foreign body + abnormal flow) 

 

 

69

What is this?

Q image thumb

- Passive congestion: caused by right heart failure due to backup of blood inadequately pumped out of heart; associated with gross pathological finding of nutmeg liver

- Hemorrhagic necrosis spanning multiple lobules alternating with steatotic areas (can be acute or chronic) 

71

What is going on here?

Q image thumb

- Main bronchus filled with frothy, proteinaceous edema fluid from the alveoli -> pulmonary edema

- Adjacent main pulmonary artery below the bronchus

72

What is this, and what might cause it? What symptom would it cause?

Q image thumb

- Saddle (b/c in pulmonary trunk) pulmonary thromboembolism: very common, and most come from DVT in legs -> most are clinically silent 

- Dyspnea: short time-frame before death -> right heart still trying to compensate, and will dilate, NOT hypertrophy 

1. B/c electrical system in heart on right side, pt may be dead in a matter of seconds via arrhythmia, and not necessarily hypoxia 

74

What are effusion, hydrothorax, ascites, and pericardial effusion?

- Effusion: abnormal excess fluid in a serosal body cavity

- Hydrothorax: fluid in a pleural cavity

- Ascites: fluid in abdominal cavity (peritoneal effusion)

- Pericardial effusion: exactly what it sounds like

76

What is this pathologic process?

Q image thumb

- Amniotic fluid embolism (calcifications and squamous cells); aka, anaphylaxis of delivery 

- Will commonly turn blue first, and complain of shortness of breath, and may die w/in a couple mins 

- Typically (statistically) a male infant 

- Syndrome of sudden, severe dyspnea, cyanosis, and shock during delivery causing acute lung injury (ALI), and disseminated intravascular coagulation (DIC)

- Appears to involve abnormal maternal response to fetal tissue exposure associated w/breaches of maternal/fetal physiologic barrier during parturition -> response and subsequeny injury appear to involve pro-inflammatory mediators similar to that seen with classic systemic inflammatory response syndrome (SIRS)

78

What are these basophilic cells?

Q image thumb

- Platelets: anuclear cellular components of blood important in initiation and propagation of clotting 

1. Come from megakaryocytes, which do have nuclei 

2. Younger platelets tend to be larger (may be a problem if you see a lot of these, i.e., bleeding or Glanzman thrombastenia)

- Platelet deficiency is the MOST COMMON and MOST IMPORTANT cause of pinpoint hemorrhages (petechiae) 

79

What is a saddle embolus?

A PE in the pulmonary trunk

80

What is platelet activating factor?

- Sepsis causes phospholipase A2 in cell membranes of platelets, endo cell, neutrophils, monocytes, and o/cells to make acetyl glycerol ether phosphocholine, or PAF

- B/t 100 and 1000x more potent than histamine in inducing vasodilation and increased vascular permeability –> activated platelets and promotes platelet aggregation

- Also promotes leukocyte adhesion to endo cells, chemotaxis, degranulation, and oxidative burst that enables microbial killing in leukocytes 

81

What is thrombotic thrombocytopenia purpura?

Over-activity of von Willebrand factor due to abnormally large multimers of it leads to tendency to clot in small blood vessels, then bleed from having used up too many platelets and clotting factors 

83

What is air embolus?

- Can be caused by getting air into IV infusion, sudden change in atmospheric pressure, chest wall injury, or back surgery in prone position

- Generally, >100 mL needed to have clinical effect, but can be fatal

84

You have a critically ill, comatose pt failing to respond to fluid resuscitation - what labs (2) should you check, and why?

- Check lactate and amylase to look for dead bowel

85

What kind(s) of shock are these hands characteristic of? Describe them (more than just their color).

Q image thumb

- Cyanotic, mottled hands suggestive of cardiogenic or hypovolemic shock 

- Especially likely to be cyanotic if lung disease 

- Cold, sweaty (clammy) hands 

NOTE: this image was contrasted to a pair of "normal-looking" hands to show that either set could be characteristic of a pt in shock (both sets would be cold)

85

What Ab test is associated with mixed CT disease?

Anti-U1 RNP  (anti-RNP not otherwise specified)

85

What Ab test is associated with granulomatosis with polyangitis (Wegener's)?

Anti-proteinase-3 

(diffuse cytoplasmic anti-neutrophil cytoplasmic, C-ANCA)

86

What tissue is this? What are the deep red cells? The deep purple ones? The ones with the central nuclei?

Q image thumb

- Microscopic brain pathology correlated with decreasing mental status of shock 

- Red: dead neurons 

1. As early as 3-4 min after losing glucose/O2 supply, cells begin to die, but not visibly dead, shrunken, and hypereosinophilic until after 12 hours 

- Purple: neurons 

- Central nuclei: macrophages (microglial cells) 

87

What is edema? What about pitting edema?

- Edema: swelling of tissue due to increased fluid in interstitial tissue spaces; can be localized or generalized

- Pitting edema: finger pressed on edematous subcutaneous tissue leaves temporary impression

 

88

What is the prognosis for systemic sclerosis?

- Age, gender adjusted mortality rate increased 5-8 times. 

- Death most commonly due to extracutaneous organ involvement: pulmonary HTN, renal crisis, or aspiration pneumonia

89

What is this?

Q image thumb

Anasarca: generalized edema (systemic)

89

What is the tx for pts w/autoimmune disease or transplantation? Provide some examples.

- Immunosuppressive therapy

- Some immunosuppressive drugs are chemotherapy agents also used for treating cancer, incl. methotrexate and cyclophosphamide

- Corticosteroids are commonly used in treating autoimmune disease and are commonly categorized as immunosuppressive, but are also categorizable as anti-inflammatory agents

90

What are the epidemiology and pathogenesis of Sjogren syndrome?

Epi: uncommon; 90% in 35-45-year-old women. Primary form less common (40%) than secondary (60%)

Pathogenesis: thought to be T lymphocyte-mediated immunological attack of some self-antigen in ductal epithelial cells of these glands or an antigen in cells in these glands infected by some virus that has a tropism for the epithelial cells of these specific glands. Sometimes involves submucosal glands in the nasopharynx, upper airway and/or vagina

91

What are rheumatologists?

  Specialists in autoimmune disease

92

What congenital deficiency might cause systemic lupus erythematosus?

- Congenital deficiency of complement C1q, C2 or C4 can impair the clearance of apoptotic cells

- Nucleic acid fragments from these uncleared cells can lead to anti-nuclear antibodies (ANA) formation, and the prototype multi-organ autoimmune disease systemic lupus erythematosus

93

What is going on here?

Q image thumb

Hematoma: hemorrhage enclosed in tissue (ear, in this case; -oma means mass)

95

What are the 4 factors that determine the likelihood of infarction?

1. Organ’s vulnerability to hypoxia (neurons die after 4 minutes of ischemia, cardiac myocytes after 20 minutes)

2. Rate of devo of vascular occlusion (if slow, allows collateral circulation to devo)

3. Nature of organ’s blood supply (dual blood supply protective, i.e., liver)

4. Oxygen content of blood 

96

This is some microscopic pathology correlated with decreasing urine output of the syndrome of shock. What is the manifestation of early shock in these renal tubular epithelial cells?

Q image thumb

- Renal tubular epithelial edema consistent with early or mild shock (earliest finding in acute kidney injury)

- Hydropic (ballooning) degeneration and swelling of tubules -> not much lumen 

- Glomerulus looks normal (important b/c these do NOT regenerate)

 

97

Should organ transplant biopsies be evaluated for infections? If yes, which ones?

- ALL organ transplant biopsies must be evaluated for ALL sorts of infections, including: 

1. Viral infections: CMV, HSV, adenovirus, etc., all ID'd by immunostains

2. Fungal infections: candida, aspergillus, histoplasma, etc., ID'd by “special stain,” aka Grocott or methenamine silver

3. Mycobac. infections like TB (“acid-fast stain”)

4. Protozooal infections like toxoplasmosis (ID'd by immunostain)

5. Garden variety bacterial infections, i.e., S aureus and Pseudomonas aeruginosa (identifiable by Gram stain)

NOTE: effects of any infection must be differentiated from those of any rejection. Transplant pts can have simultaneous infection and rejection.

98

What is hyperemia? What is the most common cause?

- Active increase in arterial blood flow, causing abnormal reddish coloration due to presence of excess oxygenated blood in tissue; inflammation is the most common cause 

- Both hyperemia and congestion are common, but not serious (abnormally large amount of blood where it belongs)

100

What is the pathogenesis of systemic sclerosis?

- Abnormal immune response + vascular damage = increased growth factors leading to fibrosis

- CD4 T-cells responding to unidentified Ag release cytokines, stimulate fibroblasts to produce collagen

- Microvascular disease: intimal proliferation, capillary dilatation, endothelial injury (increased vonWillebrand factor) + platelet activation leads to fibrosis

- Genetics poorly understood, but HLA-II and fibrillin-1 genes implicated

100

What is graft-versus-host disease?

- Cells from transplanted organs, esp. lymphocytes, move to different parts of recipient's body, so every transplanted pt. is a chimera -> donor lymphocytes commonly see cells around them as foreign and attack

- GVHD is attack and injury of host organs by donor lymphocytes: 

1. Skin: generalized erythematous rash, which goes on to cause fibrosis similar to systemic sclerosis

2. Liver: biliary and hepatocytic injury, manifested clinically by jaundice and elevated liver transaminases

3. GI tract: injury of the epithelium, manifested clinically by bloody diarrhea

- In all affected organs, attacked cells die by apoptosis

- Usually manifest early after transplant, but can be late

101

Why is amniotic fluid embolism so important?

AMNIOTIC FLUID EMBOLISM HAS 50% MORTALITY RATE, CAUSES 10% OF MATERNAL DEATHS IN US, AND LEAVES 85% OF SURVIVORS NEUROLOGICALLY IMPAIRED 

103

A 55-year-old white male lawyer with a history of smoking and ethanol use comes to the emergency department with epigastric abdominal pain and nausea.  His temperature is 37 degrees C (98.6 degrees F), pulse 110/minute, blood pressure 110/60 mm Hg and respirations 22/minute.  He is confused.  His abdomen is tender.  His skin is cool, clammy and cyanotic. What is this a classic clinical scenario for?

Hemorrhagic shock due to bleeding peptic ulcer in a patient with lung disease from smoking

103

What 2 antibody tests are commonly associated with RA?

1. Anti-cyclic citrullinated peptide (anti-CCP)

2. Anti-nuclear (ANA)

 

103

Are positive Ab tests enough to dx disease?

- No: finding these Abs does NOT make dx of disease

- Dx requires “clinical-pathologic correlation" because many normal people have these Abs w/o these diseases

 

IMPORTANT CONCEPT: Many people with no apparent rheumatological disease have antibodies associated with rheumatological disease, and should not be falsely diagnosed on the basis of serology alone

104

What is this condition, and what are its 3 pre-disposing factors?

Q image thumb

- Thrombosis 

1. Endothelial injury 

2. Abnormal blood flow 

3. Hypercoagulability 

105

What is DIC?

- Thrombus formation in small blood vessels all over body

- Complication of sepsis, metastatic cancer, multi-organ severe trauma, and other conditions

- First manifestations are brain malfunction – altered behavior, confusion, lethargy, coma

- Followed by lungs (dyspnea, hypoxemia), heart (failure, rhythm disturbance), kidney (falling urine output)

- Hemoglobin falls b/c RBCs fragmented when pushing through microvascular thrombi; platelets and clotting factors fall too b/c used up in thrombi –> coagulopathy: tendency to bleed 

106

What 2 antibody tests are associated with Sjogren syndrome?

1. Anti-SSA (= anti-Ro)

2. Anti-SSB (= anti-La)

108

How does turbulent blood flow promote thrombosis?

- By activating, sometimes even injuring endothelial cells, and by creating countercurrents (eddies) creating local pockets of stasis 

109

What is Virchow's triad?

- 3 predisposing factors for thrombosis:

1. Endothelial injury (most IMPORTANT b/c pro- and anti-coagulant factors): hemodynamic stress of HTN, toxicity of hypercholesterolemia, products absorbed from smoking

2. Abnormal blood flow: turbulence – esp. over ulcerated atherosclerotic plaques; stasis – esp. in arterial aneurysms or with deformed sickle cell erythrocytes

3. Hypercoagulability 

110

Where do mural thrombi tend to occur? Why?

 

- On wall of heart

- Sites of MI or areas of heart chamber dilation

- Turbulent flow + stasis

111

What are Protein C/S and antithrombin III deficiencies?

- Rare, inherited causes of hypercoagulability b/c these people are deficient in one of these important anticoagulants 

- Affected individuals typically present with venous thrombosis and recurrent thromboembolism, beginning in adolescence or early adulthood 

- AT3: two defects, wibble and wobble, characterized as resulting in substitutions of single AA at beginning of beta sheet of AT3 

1. Substitutions resulting in polar AAs in this location decrease activity and survival of enzyme (wibble) -> clinically, the wibble gene is associated with greater risk of thrombosis early in life (second decade) 

112

What are paradoxical emboli?

Pass through patent foramen ovale or atrial septal defect to go to organs besides lung (rare) 

114

What is this?

Q image thumb

A thrombus

115

What is the condition in this blood vessel?

Q image thumb

Recanalization

116

What is hemostasis? What are its three regulatory components?

- Formation of a blood clot (hemostatic plug) at site of vascular injury

- Regulated by three components:

1. Vascular wall (endothelium)

2. Platelets

3. Coagulation cascade 

117

What is the numerical criterion for shock?

- Shock is a syndrome, NOT a number 

- Syndrome of total body ischemia (concept of ischemia generalized to the whole person)

1. Parts of the syndrome include: a) decreasing mental status (confusion, lethargy, delirium, coma), b) decreasing urine output

2. If hypovolemic/cardiogenic: cool, clammy, cyanotic skin -> vasoconstriction peripherally to try and keep BP up

3. If septic: warm, flushed skin (sometimes, but can't count on this) -> vasodilation 

118

What is deep vein thrombosis?

- Asymptomatic in 50% of patients because collateral venous channels compensate for them

- May be dx by ultrasound, but can be difficult in overweight/obese –> often dx when embolized to lungs

Note: MAJOR RISK OF PULMONARY EMBOLIZATION FROM DVT IN LEG COMES WITH THROMBOSIS AT OR ABOVE KNEE (in iliac, femoral, or popliteal veins)

120

What is autoimmune polyglandular syndrome type I?

- Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

- Mutation in AIRE gene causing broad-spectrum autoimmune disease 

1. Hypoparathyroidism 

2. Candidiasis 

3. Adrenal insufficiency

 

122

What are PAMPs? What are they bound by?

- Various microbial cell wall and internal elements, incl. bacterial cell wall lipoproteins, lipopolysaccharides, fungal cell wall components and bacterial/viral nucleic acids

- Bound by:

1. TLRs (membrane)
2. G-coupled receptors
3. Nucleotide oligomerization domain proteins: NOD1 and NOD2, in cytosol

123

Name 7 secondary hypercoagulable states.

- Surgery

- Cancer

- Trauma

- Bed-ridden state

- Disseminated intravascular coagulation

- Heparin-induced thrombocytopenia

- Antiphospholipid syndrome 

124

Would you give an antibiotic to treat this cause of shock?

Q image thumb

No- thromboembolism (cardiogenic or obstructive, not septic)

125

What is anasarca? What is its most common cause?

- Anasarca: generalized edema

- The most common cause of generalized edema is heart failure

126

This patient died of shock. Which type? What caused it?

Q image thumb

- Cardiogenic shock 

- Hemopericardium, making it impossible for the heart to fill (confined space)

- Heart failure due to pericardial fluid, making it impossible for the heart to fill its cardiac tamponade (of course, there was a component of hemorrhagic shock too; could call it hypovolemic, but only if bleeding elsewhere too) 

1. If just fluid (and not blood), easier to treat, b/c you can drain it

 

127

What are these? Describe all three examples.

Q image thumb

- Petechiae: tiny (1-2 mm) hemorrhages due to platelet deficiency

- Purpura: medium (3-10 mm) hemorrhages due to vasculitis, vessel fragility, etc. 

- Ecchymoses: larger (over 1 cm) subcutaneous hemorrhages that go from red-blue to blue-green to gold-brown as hemoglobin breaks down (frequently called bruises) –> NOT always due to trauma

 

128

What is an embolism?

Detached, intravascular solid, liquid, or gaseous mass carried by blood to a site distant from its point of origin

129

How does surgery create a HS state?

- Cutting of blood vessels activates platelets and clotting factors that may get swept into general circulation

- At the same time, anticoagulation therapy risks bleeding at sx site

Note: SX TO TREAT MORBIDITY CAUSES MORBIDITY, INCLUDING HYPERCOAGULABILITY, ADHESIONS, AND OTHER CONDITIONS 

130

What are these?

Q image thumb

Lines of Zahn 

131

What 3 antibody tests are associated with lupus? Neonatal? Subcutaneous?

1. Anti-Smith (anti-Sm)

2. Anti-double-stranded DNA (anti-dsDNA)

3. Anti-nuclear (ANA)

 

Neonatal and subcutaneous: 1) Anti-SSA (= anti-Ro), 2) Anti-SSB (= anti-La)

133

What is Prothrombin G20210A mutation?

 

- Ssecond most common inherited HS (2% of whites)

- 3x risk of venous thrombosis 

- Many heterozygous patients have no VT, or only have VT when combined with acquired HS (i.e., woman on contraceptives or man on long plane ride)

134

What class of immunosuppressant drugs commonly causes kidney damage? How do they do this?

- Calcineurin inhibitors are nephrotoxins, so kidney transplant biopsies must be evaluated for histological manifestations of toxicity of these drugs

- They can harm the kidney by causing vasoconstriction with no morphologic change (functional toxicity)

- They can also visibly harm renal tubules w/structural toxicity manifested by (1) isometric (uniformly sized) vacuolization of tubular epithelial cell cytoplasm, (2) tubular calcifications, and (3) giant mitochondria

135

What are the causes and symptoms of PE?

- Very common

- Many from DVT in legs, usually from thighs; some from pelvic veins

- Increasing #’s from PICC (peripheral inserted central catheter) lines in arms

- Most (up to 80%) clinically silent because too small to cause symptoms

- If symptomatic, one and only symptom tends to be DYSPNEA

136

What is secondary hemostasis, and what are its mediators?

- Coagulation cascade activate by tissue factor (membrane-bound pro-coagulant made by endothelium, aka clotting factor III) and platelet factors

- Culminates in conversion of fibrinogen to fibrin by activated thrombin
- Thrombin also stimulates platelets to release thromboxane A2, activates monocytes and lymphocytes, and stimulates endo cells to adhere to neutrophils and release NO, tissue plasminogen activator, and prostacyclin 

137

What is neurogenic shock?

A form of vasogenic shock w/vasodilation due to spinal cord injury of spinal anesthesia causing acute loss of SYM NS maintenance of normal level of vasoconstriction

 

 

138

What is Trousseau syndrome?

Aka, migratory thrombophlebitis: simultaneous VT and inflammation at multiple sites due to malignant tumors

139

What is systemic thromboembolism, and where is it most commonly FROM and TO?

Thromboembolism to any organ BUT the lung -> most commonly FROM the heart (80%) and most commonly TO the legs (75%) and brain (10%) 

141

What polymorphisms are associated with multiple sclerosis?

- Polymorphisms in genes for IL-2 receptor (CD25) and IL-7 receptor alpha chains -> these polymorphisms are apparently associated with dysfunction of Treg cells 

- MS presents in middle-aged patients with wide range of neuro signs and symptoms due to autoimmune attack on myelin coating of axons

 

143

What is the definition of Sjorgen syndrome?

- Autoimmune, chronic inflammatory disease of lacrimal glands and salivary glands, causing dry eyes (kerato-conjunctivitis sicca) & mouth (xerostomia)

- Primary form: limited to eyes and mouth, also called sicca syndrome

- Secondary form associated with other autoimmune diseases: RA (most common), lupus, polymyositis, systemic sclerosis, vasculitis or thyroiditis

- Can have extraglandular involvement of kidneys, joints, skin, muscle, peripheral nerves and even brain.

145

What are biologic response modifiers? Provide 3 examples.

- Targeted therapies (aka, biologics) used in treating various autoimmune diseases

- EX: Infliximab (blocks TNF-alpha), Belimumab (Ab to B-cell activating factor), and Rituximab (Ab to CD20 on B lymphocytes)

 

147

Describe arterial thrombi.

- Rich in platelets (white thrombi)

- Usually at sites of endo injury, most often ulcerated or ruptured atherosclerotic plaque (bigger = more likely to ulcerate and rupture) that have already narrowed lumen

- More likely than venous thrombi to become occlusive and totally block off lumen (veins have thinner walls and can stretch to accommodate)

 

148

What is complement C4d?

- A degradation product of activated complement C4

- Deposited in peri-tubular capillaries in some cases of kidney transplant rejection

- Also deposited in some cases with no other evidence of rejection, so positive C4d staining has to be combined with histological evidence of rejection and the finding of donor-specific antibodies in the recipient’s blood before antibody-mediated rejection is diagnosed.  Each parameter scored, commonly on scale from 0 to 4

149

How do normal endothelial cells restrict hemostasis to where it is needed?

- Inhibit platelets with prostacyclin, NO, and adenosine diphosphatase

- Express thrombomodulin, protein C receptors, heparin-like molecules, and tissue factor pathway inhibitor

- Also secrete plasminogen activator, which activates fibrinolysis 

151

What is the condition in this artery, and what cells are most responsible for its execution?

Q image thumb

- Organizing arterial thrombus infiltrated by fibroblasts (elongated blue cells)  -> healing wound

- If you have a thrombus that organizes like this, you will not have blood flow through here again (b/c there does not appear to be any re-canalization happening, and it is way too late for heparin to open this back up)

 

REMEMBER: organization = fibroblasts 

152

A 65-year-old south Asian male trader with a history of smoking, hypertension, obesity, diabetes and dyslipidemia comes to the emergency department with squeezing substernal chest pain and dyspnea.  His temperature is 37 degrees C (98.6 degrees F), pulse 130/minute, blood pressure 80/30 mm Hg and respirations 30/minute.  He is confused.  He has diffuse bilateral pulmonary crackles.  His skin is cool and clammy. What is this a classic clinical scenario for?

Cardiogenic shock due to large acute myocardial infarction

154

How does decreased colloid osmotic pressure affect the interstitium surrounding blood vessels? How might this be different in the lungs?

- Allows solutes in the interstitium around blood vessels to pull water out of the blood 

- The interstitium around the pulmonary alveolar capillaries is air, and cannot do this

156

What is the microscopic pathology of systemic sclerosis?

- Skin: dense collagen deposition in dermis with decreased appendages. Thinning of epidermis, loss of rete pegs. Perivascular infiltrates of CD4 T-cells. Thickening of capillary/arterial basal lamina

- Kidneys (involved in about 67%): vascular changes promote hypertension and renal failure. Intimal thickening of interlobular arteries leading to ischemia and infarction 

- Lungs (involved in over 50%): vascular changes promote pulmonary hypertension and interstitial fibrosis

157

When does immunological rejection of foreign tissue occur? What mediates this attack?

- Kidney, liver, lung, heart or other organ transplanted from one person into another person elicits an immunological rejection of the foreign tissue unless they are identical twins

- Usually mediated by T lymphocytes and generally involves both cellular and antibody-mediated mechanisms

158

What is the difference between the older and newer parts of arterial thrombosis?

 

- Older parts –> organized/densely adherent to blood vessel

- Newer parts –> most likely to break off and be carried with blood stream (embolization)

160

What are the 3 main causes of shock? Why is it important to distinguish b/t these?

1. Decreasing circulating blood volume

2. Decreased cardiac output

3. Sepsis

–> may have more than one at a time, but it is important to categorize it b/c TREATMENTS ARE DIFFERENT

 

Other causes include: anaphylaxis, SIRS, and neurogenic causes
 

161

What is the most important concept about the relationship b/t sx and morbidity?

Surgery to treat morbidity causes morbidity, including hypercoagulability, adhesions, and other conditions

162

Describe pulmonary edema (the most common cause, lab values, and the major sign/symptom).

- Most common cause is left heart failure: buildup of pressure in left ventricle, atrium, pulmonary veins and capillaries

- Also caused by acute lung injury, acute respiratory distress syndrome (ARDS), hypersensitivity reactions, pneumonia, and renal failure

- Typically a clear frothy fluid (pink if blood mixed in) in alveoli, and when severe, in airways

- Major symptom: dyspnea; major sign: pulmonary crackles 

- Lab Values:

A. 10 mm Hg –> upper limit of normal

B. 20 mm Hg –> fluid starts to transudate out into interstitium

C. 25 mm Hg –> “” alveoli, associated with moist pulmonary crackles

163

What is this? What symptoms would it cause?

Q image thumb

- Fat embolism of adipocytes (large, clear cells) and other bone marrow cells (hemopoietic cells -> bone marrow embolism) 

- Most commonly from long bone fractures 

- Most clinically silent, but can cause syndrome of sudden onset of dyspnea, tachypnea, tachycardia, irritability, restlessness, anemia, and thrombocytopenia (usually 1-3 days post-trauma)

164

What is molecular mimicry? Provide an example.

- An infecting microbe can have an antigen sufficiently similar to one of yours that acquired immune response becomes autoimmune reaction

- EX: acute rheumatic fever, an autoimmune inflammation of the heart (lining, muscle and covering) triggered by GAS pyogenes pharyngitis (“strep throat”)

165

This patient experienced sudden, severe pain in this foot. What is the descriptive term for it, and what caused it? What are the two most important things to remember about this cause?

Q image thumb

- This is mottling, a manifestation of ischemia (slowing, or blockage of bloodflow)

- The sudden onset should you make you think of an embolus (this is an emergency) - SYSTEMIC THROMBOEMBOLIS

1. Most commonly from the heart

2. Most commonly to the legs (or brain) 

166

What is cardiogenic shock?

- Due to MI, cardiac arrhythmia messing up heart signaling mechanism, PE obstructing the output of the right heart, or hemopericardium squeezing the cardiac chambers, obstructing filling –> cardiac tamponade (must remove blood quickly; can also call this and PE, obstructive shock)

- WEAK, RAPID (thready) PULSE, and COOL, CLAMMY, sometimes CYANOTIC SKIN

- TX: assist heart

- Least common of the 3 types, and usually due to failure of heart as pump due to heart disease 

167

An 18-year-old white female goes off to college, takes up smoking and starts oral contraceptive therapy.  She calls her mother one evening to say she suddenly felt short of breath, most likely due to pulmonary thromboembolism due to deep venous thrombosis due to primary (congenital/genetic)...?

- Activated protein C resistance (Factor V Leiden mutation)

168

In the case of lymphatic obstruction, where does the fluid typically go?

- Not a common cause of edema, but the obstruction is more common in the pleura, so the fluid pours into the pleural space 

169

Can infections prevent autoimmune disease?

- Yes: epidemiological and experimental evidence

- As incidence of infectious diseases has fallen in developed countries, the incidence of autoimmune diseases has risen

- The postulated mechanism is stimulation of IL-2 production essential for maintaining regulatory T cells (Tregs) 

170

Where do venous thrombi tend to occur?

- Clinically most important in legs, arms, pelvis

- Sites of stasis, like venous valves in legs, esp. in sedentary folks (tend to grow on side closer to heart?)

171

What manifestation of shock is this?

Q image thumb

- Shock (nutmeg) liver: centrilobar necrosis and hemorrhage 

- Blood pours out from sinusoids; congested around central vein, so ones closer to the center are dead and dying

- Correlates with high ALT/AST 

172

What are four reasons that thrombi inevitably form around vascular catheters?

1. Endothelial injury 

2. Impeded blood flow (stasis) 

3. Thrombogenicity of foreign material 

4. Turbulent blood flow

173

What is this?

Q image thumb

Congestion (blue, venous blood) in the esophagus

174

How does shock relate to vital signs?

Q image thumb

Vital signs are late responders to shock, esp. in young people

175

What antibody test is associated with CREST syndrome?

Anti-centromere

176

What are the diagnosis, treatment and prognosis for systemic lupus granulomatosus?

- Diagnosis: ANA (present in 100%, but also up to 15% of normals), anti-double-stranded DNA or anti-Sm antibodies (much more specific), hematologic abnormalities (anemia, thrombocytopenia, etc., present in 100%), proteinuria, urinary red cell casts, kidney biopsy

- Treatment: corticosteroids and immunosuppressive medications

- Prognosis: 90% 5-year survival, 80% 10-year survival

177

What is Belimumab?

- Trade name Benlysta

- Antibody to B-cell activating factor  

178

What is this?

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- Periorbital edema

1. Localized, possible allergic reaction

- Edema: swelling of tissue due to increased fluid in interstitial tissue spaces 

179

What is infarction? How is it related to ischemia?

- Infarction: death of an organ or tissue when reversible inadequacy of blood supply (ischemia) has not been fixed before it is too late -> while infarction is common and serious, you want to concentrate on how to dx ischemia so it does not get to this point 

180

What is a mycotic aneurysm?

- Localized out-pouching of an artery containing infected thrombus (esp. in aorta)

- Infection is bacterial, and rarely fungal –> piece of vegetation in heart breaks off and travels to site in artery, or bacteria traveling in bloodstream drop off on thrombus

- Tends to occur with necrotizing infection, when exotoxins from bugs or lysosomal products from leukocytes injure the artery, which balloons out at site of injury

- Life-threatening and treatable, but uncommon

181

What is this?

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- ALI: intermediate phase (first week) -> edema condensed into alveolar hyaline membranes (friable accumulation around alveolar walls) 

183

Why are autoimmune diseases often relapsing and remitting?

- Because immune function naturally waxes and wanes

- Intercurrent illnesses stimulate immune responses that may contribute or detract from the autoimmune disease

- Autoimmune diseases tend to remit (go away) during pregnancy when immunity naturally declines

185

What is global anoxic encephalopathy?

Resuscitation in less than 20 minutes, causing entire brain to swell, which can be fatal due to herniation of cerebellar tonsils into foramen magnum, compressing brainstem respiratory center 

186

How can emboli cause pulmonary HTN?

Can be a result of numerous small emboli –> may occur all at once (shower of emboli) or, more commonly, a few at a time, each asymptomatic until critical point is reached, and pt. has DYSPNEA 

187

What is the underlying cause of autoimmune diseases?

- Failure of self-tolerance 

- Autoimmune diseases develop when genetically susceptible individuals experience an environmental trigger such as tissue damage or infection that generates self-reactive lymphocytes 

188

What is Factor V Leiden mutation?

- Mutation in Factor V that makes it resistant to cleavage and inactivation by Protein C -> important antithrombotic counterregulatory pathway lost 

- 2-15% of Caucasians carry single-nucleotide mutation: Glu to Arg mutation at AA 506 

- Heterozygotes have 5-fold increased relative risk (RR) of venous thrombosis (VT)

189

What is sepsis?

- Systemic inflammatory response syndrome (SIRS) due to infection (proven or suspected), NOT a positive blood culture 

NOTE: this is how it is defined (e.g., for study purposes), but not how it is diagnosed; no need to memorize the SIRS #'s for this course b/c they are mostly used for study design (i.e., temp >38 or

 

190

What is the condition in this artery? Be specific. What do we call this layering pattern, and what does it mean?

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- Thrombosis: inappropriate formation of thrombus in a blood vessel (usually occlusive) 

1. Visible damage to the artery: atheroslerotic plaque with cholesterol crystals/clefts -> hemorrhage will raise top of plaque and create thrombus (hematoma-like)

- Lines of Zahn: layers of red and white color that indicate this thrombus formed while blood was still circulating (rather than post-mortem), adding layers to the clot over time 

192

What are the signs and symptoms of systemic sclerosis?

- Symptoms: Raynaud’s phenomenon. Numbness, tingling, cyanosis of peripheral skin. Joint pain and/or stiffness. Digestive problems secondary to decreased gut motility

- Signs: Early: edema of the hands and feet, mostly in AM. Later: thickened, hard and/or shiny skin, esp. over long bones of arms and lower legs. Mask-like immobile face and claw-like immobile hands

 

IMPORTANT CONCEPT: Puffy fingers are often the first manifestation of systemic sclerosis

193

Name the 3 principles of common sense physics that your patients' lives will depend on (in regards to catheters and clot formation).

1. The bigger the clot, the less likely (complete) dissolution becomes 

2. The bigger the vein, and the length of catheter in it, the bigger the clot inevitably formed around the catheter 

3. The longer a foreign body catheter remains in the vein precipitating more clot formation, the less likely the clot will be resolved without a trace. 

195

As a rule of thumb, hemorrhagic shock goes from progressive to irreversibly fatal when a person has lost approximately what % of blood volume?

50% of person's blood volume commonly regarded as dividing line b/t lethal and non-lethal hemorrhage

196

What is the difference between white anemic and red hemorrhagic infarction?

- White anemic: typical of solid organs with end-arterial circulation (heart, spleen, kidney)

- Red hemorrhagic: typical with venous occlusions (i.e., ovarian torsion), dual or anastomosing blood supply (lung, intestines), or with reperfusion 

197

This patient died of shock. What type? What caused it?

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- Hypovolemic (hemorrhagic) shock

- In this case, due to retroperitoneal hemorrhage (or hematoma)

198

What is one way numerous small pulmonary emboli affect the lungs (other than thrombosis)?

Can cause pulmonary hypertension - this is a chronic process that happens over a long period of time

199

Briefly describe how activated, or dysfunctional, endothelial cells promote thrombosis.

- Express less thrombomodulin, tissue factor protein inhibitor, and other anti-coagulant factors

- Secrete plasminogen activation inhibitors and down-regulate expression of tissue plasminogen activator (t-PA)

1. These things don’t start clotting, but decrease regulation of clotting

200

Describe Na retention.

- Always generalized (w/increased hydrostatic pressure and dilutional decrease in plasma oncotic pressure)

- When heart is failing, kidney helps by retaining Na, increasing vascular volume and BP (helps, to a point) 

201

Woman with swollen feet and ankles. Abdomen distended, and wave of fluid inside abdomen when pressed. Liver is enlarged, and edge is palpable about width of five fingers below right costal margin. What is going on here?

PASSIVE CONGESTION of LIVER and LOWER LEG EDEMA from right heart failure

202

What are the 3 (ish) general categories of thrombi?

- Arterial: tend to be rich in platelets ("white thrombi")

- Venous: tend to be rich in erythrocytes ("red thrombi") 

- Mural: on wall of the heart 

1. Vegetations: on heart valves -> non-bacterial endocarditis until infected, then infective endocarditis (some may also be autoimmune, e.g., Libman-Sacks endocarditis in systemic lupus erythematosus)

203

What is infarction? List some of its primary causes.

- Area of ischemic necrosis, usually due to thrombotic or embolic occlusion of artery

- Much less common causes: vasospasm, atheroma expansion by intra-plaque hemorrhage, tumor compressing artery, twisting of blood vessels (torsion or volvulus), trauma, or incarcerated hernia 

Note: INFARCTION IS DEATH OF ORGAN OR TISSUE WHEN REVERSIBLE INADEQUACY OF BLOOD SUPPLY (ISCHEMIA) HAS NOT BEEN FIXED BEFORE IT WAS TOO LATE; COMMON AND SERIOUS, BUT WHAT YOU WANT TO CONCENTRATE ON IS HOW TO DX ISCHEMIA 

204

At what level does your hemoglobin need to be for you to experience cyanosis?

5 mg/deciliter

205

What is polycythemia vera?

- Autonomous proliferation of erythroid line bone marrow cells, resulting in abnormally large # of erythrocytes

- Promotes stasis 
 

206

What is the gross pathology of systemic sclerosis?

- Skin (100% of cases): affected areas initially edematous, ultimately fibrotic -> begins in face and fingers, progresses proximally

- Decreased mobility leads to masklike face and clawlike hands

- GI Tract (90% of cases): fibrous replacement of muscular wall, most commonly in esophagus. Lower esophageal sphincter dysfunction and decreased peristalsis cause gastroesophageal reflux and Barrett metaplasia

208

What is this? What are some common causes?

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- Small, subcapsular, wedge-shaped, peripheral infarct in a fixed section of spleen (white b/c spleen does NOT have dual blood supply)

- Usually due to thrombotic or embolic occlusion of an artery -> much less common causes: vasospasm, atheroma expansion by intraplaque hemorrhage, tumor compressing artery, twisting of blood vessels (torsion or volvulus), trauma, or incacerated hernia

209

List the 6 sources of primary hypercoagulability. In this course, which of these will your patient most likely have?

Congenital or genetic; diagnosed with a coagulation profile

1. Factor V Leiden (main one to remember)

2. Prothrombin G20210A mutation: elevated prothrombin levels (1-2% of population) 

3. Methylenetetrahydrofolate reductase homozygous C677T mutation 

4. Anti-thrombin 3 deficiency 

5. Protein C deficiency 

6. Protein S deficiency 

211

What are the 7 sources of secondary (acquired) hypercoagulability? Provide brief descriptions.

 

In this course, which of these will your patient almost certainly have?

1. Surgery: release of tissue factor from damaged endo

2. Cancer: release of tissue factor due to tissue damage (incl. necrosis)

3. Trauma 

4. Bed-ridden state 

5. Disseminated intravascular coagulation (DIC): coagulation, but pts bleed b/c they've used up all their platelets and factors -> still don't want to give them platelets/factors b/c they will burn through these too, making things worse (often a "no-win" situation, but may give heparin)

6. Heparin-induced thrombocytopenia: Ab-induced response that make platelets stick together; multiple different Abs -> in pts that have previously received heparin b/c an immunological response

7. Antiphospholipid antibody syndrome: endo injury due to self-Abs bouncing around (lupus anti-coagulant in test tube) 

212

Where is arterial thrombosis clinically most important?

 IN CORONARY ARTERIES, CEREBRAL ARTERIES, AND FEMORAL ARTERIES 

214

What happens in the final stage of coagulation?

Thrombin converts fibrinogen to fibrin

216

What Ab test is associated with microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (Churg Strauss)?

Anti-myeloperoxidase 

(= perinuclear anti-neutrophil cytoplasmic, P-ANCA)

218

Describe septic shock. How does it manifest itself in the skin, and why is it important to distinguish this from other types of shock?

- Distributive shock b/c  widespread vasodilation, maldistributing blood volume diffusely throughout body, returning too little to heart and lungs to oxygenate and pump –> similar to anaphylactic shock (aka, vasogenic, or distributive shock)

- WARM, FLUSHED SKIN; decreasing urine output in all three types of shock 

- Important to distinguish this from other types and administer AB’s as quickly as possible (7.6% increase in mortality for each of the 6 hours after the 1st hour)

NOTE: SEPSIS IS NOT A POSITIVE BLOOD CULTURE, NOT EVEN CLOSE –> majority have (-) cultures

220

What are the diagnosis, treatment, and prognosis for Sjogren syndrome?

- Diagnosis: Anti-SSA (= anti-Ro) and/or anti-SSB (= anti-La) antibodies (not entirely specific). “SS” = Sjogren syndrome

- Treatment: Topical therapy of dry eyes, dry mouth and other dry mucosal surfaces, systemic cholinergic agents to stimulate secretions. Hydroxychloroquine, sometimes rituximab for extraglandular disease

- Prognosis: usually not too bad, but especially notorious for developing lymphoma

222

What is von Willebrand disease?

Deficiency of von Willebrand factor, leading to a tendency to bleed excessively with surgery or menstruation 

223

Why are autoimmune diseases usually chronic and progressive?

- Because self-antigens that are target of the disease remain present for as long as person lives

- Also, tissue damage releases new antigens, stimulating added immune rxns -> epitope spreading

  

224

What is the pathologic condition in this coronary artery? What is the most important factor predisposing it (and its 3 most common risk factors)?

Q image thumb

- Thrombosis 

- Endothelial injury 

1. Hemodynamic stress of HTN 

2. Toxicity of hypercholesterolemia 

3. Products absorbed from smoking can increase endothelial procoagulant factors or decrease their anticoagulant factors enough to cause thrombos

226

Why is categorizing shock nearly as important as recognizing it?

- Because this determines treatment 

227

What are vegetations?

- Thrombi on the heart

- Mostly non-bacterial thrombotic endocarditis (marantic endocarditis) until infected –> the bigger it is, the more likely is infected b/c organisms added to growing clot

- May be autoimmune, i.e., Libman-Sacks endocarditis in systemic lupus erythematosus

228

What is the manifestation of later shock in these renal tubular cells? 

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- Renal acute tubular necrosis consistent with later, or worse, shock (later finding in acute kidney injury)

- Eosinophilic, shrunken tubular cells (dead) with karyorrhexis/lysis of nuclei -> coagulative necrosis 

- Kidney has one of the highest regenerative rates, so it is possible for these to regenerate and be replaced to normal (except for glomerulus, which does not regenerate at all, but does not get involved in most cases of shock, forunately)

229

How is fibrinolytic therapy for thrombosis best delivered?

- Via IV catheter at site of thrombosis, and generally only effective when given during first few hours of thrombosis

- Clot formation around these catheters inevitable, and carries risk of embolization and infection of clot (more time in = more risk, and more permanent clot)

- Peripherally inserted central catheters (PICC) in arm veins leading to explosive increase in arm DVT 

230

Name 6 type of embolus. Which is most common?

1. Thrombus (most common) 

2. Atheromatous debris 

3. Fat 

4. Air

5. Amniotic fluid 

6. Fragments of tumor 

231

What is going on here? What are the common causes?

Q image thumb

- Liquefactive necrosis after cerebral edema

- Can be localized (abscess or tumor) or generalized (encephalitis, hyponatremia, global anoxic encephalopathy, etc.)

- Hyponatremia –> causes water to enter cells, resulting in cellular swelling; swollen brain malfunctions, causing lethargy, obtundation (less than full alertness), stupor, coma, seizures, and death

- Neurons die after only 4 minutes w/o O2
 

232

What are the two major paths to self-tolerance?

CENTRAL and PERIPHERAL

233

What are the 3 most common types of shock?

1. Septic

2. Hypovolemic

3. Cardiogenic 

 

234

Describe thrombus organization.

- Ingrowth by fibroblasts, who convert thrombus to fibrous tissue, with ingrowth of new capillaries, which can coalesce to re-canalize thrombosed blood vessel

- Can occur in pneumonias, exudates, injuries, etc., and not just thrombi

NOTE: thin-walled vein can tear or collapse when you pull out long-dwelling catheter with organized thrombus around it continuous with lining of the vein 

236

What is Factor V Leiden mutation?

- Most common inherited HS (5% of whites)

- Mutation in clotting factor (CF) 5 so resistant to activated protein C –> loss of important clot-limiting regulatory mechanism

- Heterozygotes have 5x risk of venous thrombosis (VT)

- Homozygotes have 50x risk 

237

What are the 6 most common types of emboli?

1. Thrombus (overwhelmingly most common) 

2. Atheromatous debris 

3. Fat 

4. Amniotic fluid 

5. Fragments of tumor 

6. Air

238

What is Alemtuzumab?

- Ab to CD52, which is expressed at high levels by both normal and malignant B and T cells, with lower levels found on monocytes, macrophages and eosinophils

- An esp. powerful immunosuppressant, given as single dose at time of transplantation and seeming to create a permanent effect likened to AIDS

- Substantially decreases incidence of transplant rejection and increases the risk of opportunistic infection

- Trade name Campath


IMPORTANT CONCEPT: Usually a trade-off b/t efficacy and toxicity of the meds used to treat autoimmune disease and transplant rejection

239

What is this?

Q image thumb

Lung (no pathological biz)

240

What is going on here?

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- These are hemophages: hemosiderin-laden macrophages (iron from blood that has leaked into alveoli due to capillaries burst from high pressure)

- Aka, heart failure cells

- May accumulate in pulmonary alveoli in chronic sublethal left heart failure 

241

What is hemothorax?

Hemorrhage into a pleural cavity 

242

Descibe lymphatic obstruction (lymphedema), and provide two clinical examples.

- Usually localized and caused by tumor, inflammation, surgery, radiation, or scar

- Breast cancer –> orange peel

- Parasitic filariasis: fibrotic obstruction of lymph channels and nodes in legs (elephantiasis) 

243

What is Rituximab?

- Trade name Rituxan

- Antibody to CD20 on B lymphocytes

244

Why is serology important in dx of many rheumatological diseases?

- Serology = antibody testing

- Many immunologic diseases, especially the autoimmune diseases seen in rheumatology, are at least partly mediated by antibodies

 

245

What is going on here?

Q image thumb

- Acute coagulative necrosis of heart (note similarity of dead cells to fibrin thrombi) -> infarcted heart muscle

- Darker, so dead and dying -> coagulative necrosis is the most common histologic form of infarct

1. Usually apparent after 12-18 hours 

2. Usually with an acute inflammatory response, peaking at 1-2 days, followed by macros and fibroblasts 

246

What is increased hydrostatic pressure? Describe some common clinical examples.

- Pressure in fluid in equilibrium, due to gravity – higher the deeper you go b/c more weight pushing down

- Worse in legs when standing, and sacrum when lying down

- In leg –> deep venous thrombosis

- Lungs –> left heart failure

- Lower body –> right heart failure

 

247

What is self tolerance?

Lack of immunologic responsiveness to your own antigens

248

What is Waldenstrom macroglobulinemia?

- Abnormally thick hyper-viscous plasma loaded with excess IgM due to autonomous proliferation of B lymphocytes making IgM

- Promotes stasis

249

What is a fat embolus?

 

- Most commonly from long bone fractures, and most are clinically silent, but large #’s can cause syndrome of sudden onset dyspnea, tachypnea, tachycardia, irritability, restlessness, anemia, and thrombocytopenia

- Usually 1-3 days post-trauma

- Sickle cell can cause painful bone infarcts, and fat embolism from infarcted bone can be fatal

250

What is hyperacute transplant rejection?

- Occurs w/in minutes of transplantation due to large numbers (“high titers”) of pre-formed Abs in recipient immediately trashing the transplant

- Has become very rare  

 

251

Do many patients with autoimmune or rheumatological disease tend to have clinical manifestations limited to one specific disease?

- No: many patients with these disease do NOT have clinical or pathologic manifestations limited to one single specific disease

- Many patients have overlap syndromes with features of more than one autoimmune disease  

252

Why is it important to only leave catheters in when absolutely necessary?

CLOT FORMS AROUND EVERY CATHETER YOU PUT IN, BRINGING WITH IT EVER-PRESENT DANGER OF EMBOLIZATION AND INFECTION OF CLOT

253

Elderly white male with history of smoking, HTN, obesity, diabetes, and dyslipidemia presents with onset of progressive dyspnea. He wakes up at night with shortness of breath, and props himself up to sleep at night. On auscultation, he has fine crackles over the lungs posteriorly. What is going on here?

PULMONARY ALVEOLAR EDEMA from left heart failure, most likely due to silent MI

254

What tissues are most commonly involved in autoimmune diseases?

- Tend to involve blood vessels and connective tissue

- Often called collagen vascular diseases or connective tissue diseases

255

What are two of the things that thromboemboli can cause (medium vs. large)?

- Medium: can cause hemorrhagic infarction (if bronchial arterial part of dual lung supply impaired)

1. Typically red, hemorrhagic infarct b/c secondary blood supply to lungs 

- Large: acute cor pulmonale and sudden death 

1. Note: right heart failure is not the same thing as cor pulmonale, but may be a consequence of it 

256

What enteric manifestation of shock is this?

Q image thumb

- Hemorrhagic, ischemic, enteritis -> dusky bowel (manifestation of shock in the GI tract) 

- Correlates with high lactate and amylase 

- Ischemia -> infarction -> hemorrhage b/c dual blood supply to bowel via arcade 

- In case of critically ill, comatose pt failing to respond to fluid resuscitation -> check lactate and amylase to look for dead bowel

 

257

What is the gross pathology of systemic lupus erythematosus?

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- Non-erosive synovitis in 90%, pleuritis in 46%, pericarditis in 25% peritonitis (commonly polyserositis, acute, subacute or chronic), Libman-Sacks endocarditis (1-3 mm verrucous vegetations on either side of valve), moderate splenomegaly

 

258

Provide 2 clinical examples of edema that fits into two different categories.

1. Hepatic cirrhosis –> edema due to increased hydrostatic pressure in portal vein system, but also from decreased plasma osmotic pressure due to protein loss into ascites and deficient hepatic protein synthesis

- Hypoalbuminemia: secondary hyperaldosteronism (decreased plasma osmotic pressure), adding Na retention to the picture

259

What is going on here?

Q image thumb

- Ascites: fluid in the abdominal cavity 

- Localized in one body cavity, but could be systemic buildup (i.e., portal hypertension, right heart failure)

260

An older woman comes into your office complaining of flank pain. She has a fever, high P, and low BP. She has recently been put on Coumadin (Warfarin) because she had a stroke several months ago. What is this a classic clinical scenario for?

- Hemorrhagic (hypovolemic) shock due to retroperitoneal hemorrhage 

- Typically older women -> pt. could have been put on Warfarin for any # of reasons, including a heart valve problem, or pulmonary embolus 

- Ironically, this pt. is more likely to bleed to death from a retroperitoneal hemorrhage than to clot to death from whatever she is receiving an anti-coagulant for 

261

What are the signs and symptoms of systemic lupus granulomatosus?

- Symptoms: commonly relapsing and remitting: joint pain (w/o deformity) in 90%, fever (may be “fever of unknown origin”) in 83%, fatigue in 81%, weight loss in 63%, pleuritic chest pain, photosensitivity, nephrotic syndrome (edema), angina, alopecia (hair loss), myalgia 

- Signs: erythematous skin rash over bridge of nose and cheeks (“butterfly rash”) present in 50% and in other sites in 35% more, edema (first in feet), hematuria (usually only microscopic), neuropsychiatric (psychosis, seizures), oral ulcers, interarticular skin rash on fingers, peri-ungual erythema around fingernails, alopecia

262

What is azathioprine?

- Trade name Imuran

- Purine analogue that messes up DNA replication

- Used in treating systemic lupus erythematosus, RA and many other autoimmune diseases

263

What is severe sepsis? How is this related to septic shock?

- Severe sepsis: subset of sepsis w/acute organ dysfunction such that a person can't maintain homeostasis w/o intervention (ex: acute alteration in mental status, oliguria, lactic acidosis)

- Septic shock: A subset of severe sepsis –> sepsis-induced hypotension with systolic 40 mm Hg change from baseline, refractory to adequate fluid resuscitation, w/acute organ dysfunction (normalization of BP w/fluid suggests hypovolemic rather than septic)

NOTE: trauma patients may have hemorrhagic + septic shock b/c increased production of TNF, IL-1, and IL-6

264

Name and briefly describe the calcineurin inhibitors.

- Cyclosporine and tacrolimus (aka, FK506 or FK)

- Bind to intracytoplasmic receptor proteins called immunophilins. Complexes formed by these bound molecules bind to, and inhibit, a phosphatase called calcineurin. Calcineurin normally dephosphorylates intracytoplasmic nuclear regulatory proteins in lymphocytes, facilitating their translocation into nucleus and activation as intranuclear factors, promoting T lymphocyte activation and secretion of TNF, interferon-gamma, IL-2 and IL-4

- Structurally unrelated, but both block about 1/2 of calcineurin activity at therapeutic levels and require blood testing at regular intervals to determine if levels are therapeutic

- Given to transplant patients to prevent or treat transplant rejection

265

How does abnormal blood flow predispose to thrombosis?

Turbulence or stasis 

- Examples: 

1. Turbulent blood flow over atherosclerotic plaques promotes arterial thrombosis 

2. So does stasis in arterial aneurysms

266

What is organization?

- Conversion of something into fibrous scar tissue 

- Can occur in pneumonias, exudates, injuries, etc., not just thrombi

- Ingrowth by FIBROBLASTS, who convert it to fibrous tissue, with ingrowth of new capillaries, who can coalesce to recanalize a thrombosed blood vessel -> these cells are the MORPHOLOGIC MANIFESTATION of organization

- Organization is the process, not the product 

267

What is Rheumatoid Arthritis, and what is gene predisposes you to it?

- Rheumatoid arthritis (RA) is perhaps the most common autoimmune disease -> 3.6% of US F and 1.7% of M 

- Tends to involve small joints of hands and feet, esp. metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints 

- Associated w/PTPN22 gene: disease-associated variants of this tyrosine phosphatase fail to properly regulate tyrosine kinases in lymphocytes, resulting in excessive activation