Pathology Flashcards
What are the causes of localized edema?
- inflammation
- allergic rxn
- venous obstruction
- lymphatic obstruction
What are the causes of systemic edema?
(increased retention of total Na+ and H20)
- congestive heart failure
- renal disease
- hypoproteinemia (protein loss/kidney disease, decreased synthesis/liver disease, malnutrition/decreased intake)
What is hyperemia?
-increased blood flow due to vasodilation. Active process.
What are the characteristics of acute pulmonary edema?
- due to left ventricular failure–>increase hydrostatic pressure
- engorgement of capillary beds–>capillary rupture–>edna in air spaces
What are the characteristics of chronic pulmonary edema?
- persistent, less hydrostatic pressure that acute
- thickened interstitium
- “heart failure cells”-macrophages w/ hemosiderin
What are the characteristics of acute liver congestion?
- secondary to shock or hepatic vein thrombosis
- centrilobular hepatocytes more vulnerable
- central vein and sinusoids distended w/ blood
What are the characteristics of chronic liver congestion?
- due to right ventricular failture
- mottled red and yellow appearance “nutmeg” liver
- possible fatty change in mid lobular and necrosis in centrilobular
What are the three components of hemostasis?
1) endothelial cells (vessel wall injured)
2) platelets
3) coagulation cascade
What is the sequence of events that results in hemostasis?
1)exposure to subendothelium→Platelet binding and activation
2)platelet adherence/aggregation→ primary platelet plug
3) Activation of coagulation cascade at the same time as 1) and 2)
4) Last 2 steps of coagulation cascade →definitive platelet plug
•prothrombin→thrombin
•fibrinogen→fibrin
What can cause small vessel hemorrhage?
- can be secondary to congestion and ↑ hydrostatic pressure
- bleedling disorders, involving platelet deficiency
- abnormalities of coagulation
- ↑ vessel fragility
What can cause large vessel hemorrhage?
- Trauma
- Atherosclerosis
- Congenital aneurysms
- Inflammatory conditions
- Erosion caused by tumor infiltration
What are the differences between a blood clot and a thrombus?
A thrombus is:
•Result of coagulation cascade and platelet activation (blood clot is cascade only)
•Develops in vascular system or heart in living person (blood clot in extravascular)
•Often attached to underlying endothelium (blood clot not attached)
•Displays orderly layering of platelets and fibrin (blood clot randomly oriented)
What is Virchow triad?
1) endothelial injury
2) disruption of laminar blood flow: stasis or turbulence
3) blood hypercoagulability
What is the main cause of arterial thrombosis?
atherosclerotic vessel disease
What is the sequence of events that lead to artherogenesis?
1) endothelial injury to large/med arteries
2) retention of LDL and endothelial activation
3) LDL oxidation
4) formation of foam cells and propagation of chronic inflammation
5) endothelial dysfunction
6) healing by smooth muscle cells
What are the causes of cardiac thrombi?
- MI
- left atrial dilation
- atrial fib
- valvular disease (vegetation)
What are the causes of aortic thrombi?
-atherosclerosis and aneurysm, which is secondary to atherosclerosis
What are the causes of venous thrombosis?
-pockets of stagnant blood in valves
Whats the major distinction between superficial and deep vein thrombosis?
DVT are prone to embolization
What are the potential outcomes of thrombi?
1) dissolution
2) propagation
3) organization/recanalization
4) embolization
How does disseminated intravascular coagulation (DIC) lead to death?
o Systemic activation of coagulation→ intravascular fibrin deposition →thrombosis in small/mid vessels→organ failure→ death , At the same time…
o Systemic activation of coagulation→depletion of platelets + coagulation factors→bleeding→death
What activates DIC through thromboplastic substances?
- Endotoxin in gram negative sepsis
- Obstetric complications, e.g. amniotic fluid embolism, premature placental detachment
- Malignant tumors
- Traumatized/necrotic tissue
What activates DIC through endothelial injury?
- Endotoxin in gram negative sepsis
- Antigen antibody complexes
- Temperature extremes
What are the clinical symptoms of DIC?
- Pulmonary edema w/ respiratory distress
- Skin/mucous membrane bleeding
- Hemorrhage from surgical incisions
- Neurological signs
- Acute renal failure
What are the laboratory findings of DIC?
- Thrombocytopenia from platelet consumption
- Prolonged bleeding time
- Elevated fibrin split products
- Microangiopathic hemolytic anemia
What are sources of systemic thromboemboli?
1) left ventricular wall thrombi
2) left atrial wall thrombi
3) valvular vegetations
4) atherosclerotic plaques or aortic aneurysms (<20%)
5) paradoxical emboli (rare) – travel from right to left heart, e.g. through patent foramen ovale, originate from venous system
What are sources of pulmonary thromboembolism?
Mostly DVT
-saddle embolus-lodges in pulmonary artery bifurcation
What causes fat embolism?
complication of long bone fractures, physical trauma, burns →fatty marrow released into bloodstream
What is the source of atheroma embolism?
- Release of necrotic lipid debris in atherosclerotic plaque
- Affects: kidney, spleen, brain, intestine (small arteries)
- Histology: cleft like spaces from cholesterol
What causes amniotic fluid embolism?
- Amniotic membrane rupture →respiratory distress, cyanosis, collapse
- Emboli includes: epithelial cells, lanugo hair, fat, mucous droplets, intestinal discharge of fetus
- DIC initiating
What are the causes of gas embolism?
- side effect of medical care
- penetrating chest wall injury
- Decompression sickness -Caisson syndrome
What does the clinical impact of ischemia depend on?
- availability and integrity of collateral blood supply
- rate of development of obstruction
- tissue susceptibility to ischemia
- metabolic rate of tissue
What tissues do white infarcts occur in?
solid organs w/ poor collateral circulation- heart, kidney, brain, spleen
-caused by arterial occlusion
What causes red infarcts? Where does it usually occur?
- venous infarcts- hemorrhage is from capillary rupture
- in lung/liver, organs with dual blood supply or marginal collateral circulation
- necrotic tissues w/ reperfusion of necrotic area
What organs tend to have wedge shaped infarcts?
Kidney, lung, spleen
What causes Hypovolemic shock?
caused by large drop in intravascular blood volume due to:
•External/internal hemorrhage
•Fluid loss – vomiting, diarrhea, dehydration
•Plasma loss –burns
What is cardiogenic shock caused by?
- Heart pump failure
- Associated with MI, or complications associated with MI – arrhythmias, interventricular septal reupture, ventricular free wall rupture
- Pulmonary embolism
What causes generalized vasodilation shock?
- anaphylactic shock
- neurogenic shock
- septic shock
What are the stages of shock?
1) compensation (nonprogressive)-tachycardia and peripheral vasocontriction
2) impaired tissue perfusion (progressive) - prolonged vasocontriction
3) decompensation (irreversible) - loss of vasoconstriction reflex - death likely
Do you need high sensitive or specificity for a discovery test? (Might the patient have the disease?)
High sensitivity. Most patients with the disease should have a positive result.
For a confirmation test, what is the requirement for the test?
100% specificity. False positives not tolerated.
For an exclusion test, the test must be..what?
100% sensitive. False negatives not tolerated.
What are the important veins that thrombosis occurs in that results in infarct?
- renal vein
- superior sagittal sinus
- mesenteric veins
What are Grey Turner’s sign or Cullen’s sign?
Produced by hemorrhagic pancreatitis, blood in retroperitoneal space that dissects into the flanks or to the umbilicus
What are the common predisposing factors for acute pancreatitis?
Alcohol abuse and cholelithiasis
What are some less common predisposing factors for acute pancreatitis?
abdominal trauma infections hypercalcemia penetrating duodenal ulcer use of certain drugs hyperlipoproteinemia hereditary pancreatitis
What are some non specific laboratory findings in acute panreatitis?
low Cl-, high bicarb due to vomiting
low Ca++, very low w/ normal albumin means poor prognosis
high Hgb and Hct
high glucose increased glucagon, decreased insulin
elevated TGs, common in alcoholics
What are specific measurements of pancreatitis?
serum amylase and serum lipase
chronic elevations of serum amylase with little or no abdominal pain are seldom due to pancreatitis, but may be due to_____?
renal failure, decreased clearance of amylase released into serum
What is needed to diagnose MI?
1) rise in cardiac biomarkers, ie troponin-serial determinations over 12 hours In addition, need one of following a) symptoms of ischemia b)ECG changes indicative of new ischemia c) new Q waves by ECG d)imaging evidence
When can acute MI be excluded from diagnosis?
negative troponin at presentation and every 4-6 hours until 12 hours pass
What is included in a hepatitis panel for acute hepatitis?
Anti HAV IgM, HBsAg, anti-HBc IgM, anti-HCV
What do the following test results indicate?
HBsAg+ for 6 months, HBV DNA+, HBeAg+, anti-HBe-
chronic active HBV infection
HBeAg is the excreted form of the antigen
What do the following test results indicate?
HBsAg+ for 6 months, HBV DNA+, HBeAg-, anti-HBe+
chronic carrier
What mutation and gene is involved relating to Wilm’s tumor?
WT1 gene loss - deletion -nephroblastoma
What gene and cancer is related to amplification mutation?
myc is unregulated and associated with neuroblastoma
What genes are related to apoptosis and what cancers are associated?
p53 - apoptosis inducer - bladder, lung, ovary cancer
bcl-2 - apoptosis block - B cell lymphomas
What tumor suppressor genes are related to colon cancer?
APC
What gene is related to retinoblastoma and what is its functional category?
RB, is a tumor suppressor gene
What genes if loss or inactivated, associated with mismatch repair, cause colon, endometrium cancer?
MSH2, LH1, PMS1, PMS2
What are the most common types of cancer in men? What causes the most mortality? (from most to least common)
Most common cancers: 1. prostate 2. Lung 3. Colon 4. Urinary Most deaths 1. Lung 2. Prostate 3. colon 4. pancreas
What are the most common types of cancer in women? What causes the most mortality? (from most to least common)
Most common cancers: 1. Breast 2. Lung 3. colon 4. uterus Most deaths 1. Lung 2. breast 3. colorectal 4. pancreas
What are the neoplasms with single gene Mendelian inheritance?
- retinoblastoma - deletion of Rb gene
- Wilm’s tumor - nephroblastoma - deletion of WT1 gene
- neurofibromatosis - NF-1 gene
- Familial polyposis Coli - APC gene
What is CEA a tumor marker for?
colorectal carcinoma
What is AFP a tumor marker for?
hepatocellular carcinoma and neural tube defects
What is hCG a tumor marker for?
trophoblastic disease
What is hCG and AFP tumor markers for, used together?
testicular carcinomas
What are immunoglobulins tumor markers for?
multiple myeloma
What are CA15-3 and CA27-29 tumor markers for?
breast carcinoma
What is CA19-9 a tumor marker for?
pancreatic carcinoma
What is CA125 a tumor marker for?
ovarian carcinoma
Hypercalcemia associated with cancer occurs in what three settings?
- solid tumors that produce hypercalcemia
- hematologic malignancies, esp multiple myeloma and T cell lymphoma
- widespread metastatic disease involving bone
What are the laboratory findings of solid tumors that give rise to hypercalcemia in the absence of metastasis?
- hypercalcemia
- hypophosphatemia
What are the laboratory findings of patients with hypercalcemia due to metastatic cancer and osteolysis?
- hypercalcemia
- hyperphosphatemia
What cancer is the major cause of ectopic Cushing syndrome?
carcinomas of the lung, esp small cell carcinoma
Why do some carcinomas lead to ectopic Cushing disease?
produce large amounts of POMC which is converted to ACTH –>cortisol release–>cushing syndrome
What are the most common types of cancer in pediatrics versus adults?
pediatrics: 1. lymphomas 50% 2. blastomas 3. CNS tumors adults 1. carcinomas 85%
List some carcinogenic chemicals and their associated cancers.
- soot -scrotal cancer -polycyclic HCs
- aromatic amine - benzidine and naphtylamine- bladder cancer
- azo dyes - liver tumors
- nitrosamines -stomach cancer
What gene is associated with the ‘Philadelphia chromosome’ of chronic myelogenous leukemia (CML)?
ABL
What are examples of oncogenic RNA viruses?
HTLV -human t leukemia virus type I
HIV
Hep C maybe with HBV
What are examples of oncogenic DNA viruses?
- HPV
- EBV - epstein barr virus
- Hep B virus
- HHV and CMV
What are BRCA1 and 2 genes involved in?
DNA repair
Generally, what activates DIC?
- release of thromboplastic substances into the circulation
- widespread injury to endothelial cells
