Hemodynamics and Autoimmune Diseases Flashcards
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
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)
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
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
What is this? Why are there dimples in the skin?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/283/726/q_image_thumb.jpg?1659504962)
- 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
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
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
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
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
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
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
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
What is the consensus definition of sepsis?
SIRS due to infection, proven or highly suspected, meeting at least 2 of these 4 criteria:
- Fever >38 or hypothermia
- P >90/min
- Tachypnea >20/min or hyperventilation (arterial pCO2
- 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
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
What are the two “stages” of acute kidney injury (AKI)?
- Earliest finding: tubular epithelial edema
- Later, worse injury: acute tubular necrosis, but tubular epithelial cells can regenerate and be replaced (glomeruli cannot, but are not typically affected in shock)
What is the nature of the fluid on the cut surface of this lung in a patient who died of shock?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/306/685/q_image_thumb.png?1659505010)
- 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
What 5 things must you describe of any infarct, hemorrhage, tumor, or lesion?
- Size
- Shape
- Color
- Consistency, including texture (this is the only one that requires more than seeing, i.e., palpation)
- Relationships (including location and proximity to other things)
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)
What is Bernard-Soulier syndrome?
Rare deficiency of platelet Gp1b receptors for von Willebrand factor causes bleeding tendency
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
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
What are the four fates of a thrombus?
- Dissolution: dissolving by fibrinolysis (endogenous or exogenous)
- Propagation
- Embolization
- Organization (and recanalization): can occur in pneumonias, exudates, injuries, etc., and not just thrombus
What are anergic lymphocytes?
Functionally unresponsive
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)
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
What is this?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/129/393/654/q_image_thumb.jpg?1659503962)
- 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)
What is going on here? What is the most likely pathophysological mechanism of this condition?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/225/333/q_image_thumb.jpg?1659504861)
- 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
What is this and what is the most common cause?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/283/217/q_image_thumb.jpg?1659504961)
- 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)
What are the 4 fates of a thrombus?
- Dissolution: complete or partial removal of the clot by fibrinolysis
- Propagation: growth of the clot
- 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)
- 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
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)
What are the 3 TNF-alpha blockers?
- Infliximab (trade name Remicade)
- Etanercept (trade name Enbrel)
- Adalimumab (trade name Humira)
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%)
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
What are the 5 physiological categories of edema?
- Increased hydrostatic pressure
- Decreased plasma osmotic pressure
- Sodium retention
- Inflammation
- Lymphatic obstruction
BONUS QUESTION: What do you think might be going on with this lung?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/300/168/q_image_thumb.jpg?1659505003)
Terrible pulmonary emphysema and aspergillosis (fungal infection)
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
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
What is the best way to treat shock?
To treat the inciting event, and the best way to do that is to categorize it
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
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):
- TNF
- 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
- IL-6, IL-12, IL-18
- 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
- High mobility group box 1 protein (HMGB1)
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
What is the microscopic pathology of systemic lupus erythematosus?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/609/297/q_image_thumb.gif?1659505391)
- 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%
What is the relationship between catheters and clots?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/290/207/q_image_thumb.jpg?1659504973)
- 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)
Why does this activity lead to a hypercoagulable state, and sometimes thrombus?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/288/959/q_image_thumb.jpg?1659504972)
- 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
What Ab test is associated with polymyositis/dermatomyositis?
Anti-Jo-1 (one type of anti-synthetase)
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
What is this?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/267/464/q_image_thumb.jpg?1659504934)
- Hyperemia due to photo sensitivity
- Note the red color
- Arterial
What is mucin?
High molecular weight, heavily glycosylated thrombogenic proteins produced by malignant glandular tumors
How do pro-inflammatory cytokines affect leukocytes?
Upregulate expression of endo cell adhesion molecules that bind leukocytes, directing them to site of infection
What are Pembrolizumab and Nivolumab?
- Immunotherapies consisting of antibodies to PD-1
- Effective and were FDA approved for treating metastatic melanoma in 2014
What is this?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/305/515/q_image_thumb.jpg?1659505009)
Thrombus with lines of Zahn
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
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
What is going on here?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/291/452/q_image_thumb.png?1659504973)
- Marantic endocarditis (3 vegetations)
- This is the left ventricle, mitral (bicuspid) valve; thick walls are a clue
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
What is Tocilizumab?
New antibody that blocks IL-6 receptors
What is this?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/267/654/q_image_thumb.jpg?1659504935)
- 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)
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
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
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
What is this 2cm lesion?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/305/294/q_image_thumb.png?1659505008)
-
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
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
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
What are in the white matter of this brain?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/283/443/q_image_thumb.jpg?1659504962)
Petechiae (abnormal)
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
What are the collections of tiny, red dots on this organ?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/282/489/q_image_thumb.jpg?1659504959)
Petechiae, which are small hemorrhages, (and ulcer) on mucosa of the stomach
What organ/feature are we looking at? What are the dark pink things featured in the middle of the slide?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/304/817/q_image_thumb.jpg?1659505007)
- Renal glomerulus
- Fibrin thrombi/thromboemboli (blood clots) associated with disseminated intravascular coagulation (DIC)
- Waterhouse Friderichsen Syndrome
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)
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
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
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
What 2 antibody tests are associated with systemic sclerosis?
- Anti-Scl70 (anti-DNA topoisomerase); diffuse systemic sclerosis
- Anti-RNA polymerase (anti-U3 RNP)
- Anti-centromere (limited use for systemic sclerosis)
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
What are these?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/281/945/q_image_thumb.jpg?1659504959)
- Petechia: tiny (1-2mm) hemorrhages due to platelet deficiency (abnormal NUMBER or FUNCTION)
What is shock lung?
- A form of acute lung injury (ALI), formerly called diffuse alveolar damage (DAD)
- Correlated with Acute Respiratory Distress Syndrome (ARDS)
What is this?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/305/114/q_image_thumb.jpg?1659505008)
- Colonic infarct (red): ischemic bowel with necrosis and hemorrhagic infarct (dusky bowel)
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
What is the most common type of hypovolemic shock? Which of these are the most difficult to catch?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/299/580/q_image_thumb.jpg?1659504991)
- 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
What are the 3 types of thrombi?
- Arterial: rich in platelets (white thrombi)
- Venous: rich in erythrocytes (red thrombi); clinically most important in legs, arms, pelvis
- Mural: on wall of heart
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
What are the 4 stages of hemostasis at the site of vascular injury?
- Vasoconstriction
- Primary hemostasis
- Secondary hemostasis
- Thrombus and antithrombotic events
What are these?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/282/874/q_image_thumb.jpg?1659504960)
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)
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)
What does friable mean?
Will break apart (like crumbly cheese)
What are purpura?
Medium (3-10mm) bleeds due to vasculitis, vessel fragility, etc.
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
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.
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.
What is (was) going on here?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/281/822/q_image_thumb.jpg?1659504958)
- Hemoperitoneum: bleeding into abdominal and pelvic cavity (due to misdirected femoral catheter, in this case)
- Hemorrhage: extravasation of blood due to blood vessel rupture
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
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
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
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
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)
Imagine someone just pressed down on this leg with their finger- what is this? What causes it?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/283/588/q_image_thumb.jpg?1659504962)
- 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
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
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)
What is this?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/129/393/693/q_image_thumb.jpg?1659503962)
- 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)
What is going on here?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/283/970/q_image_thumb.jpg?1659504962)
- Main bronchus filled with frothy, proteinaceous edema fluid from the alveoli -> pulmonary edema
- Adjacent main pulmonary artery below the bronchus
What is this, and what might cause it? What symptom would it cause?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/286/495/q_image_thumb.jpg?1659504966)
- 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
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
What is this pathologic process?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/305/381/q_image_thumb.jpg?1659505008)
- 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)
What are these basophilic cells?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/130/282/549/q_image_thumb.jpg?1659504960)
- 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)
What is a saddle embolus?
A PE in the pulmonary trunk
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
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
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