1. neural stimulation vasoconstriction
2. endothelin
First two things that occur for primary hemostasis
GpIb- vWF
GpIIb/IIIa - fibrinogen
What does GpIb used to bind collagen?
What does GpIIb/IIIa use to bind each platelets?
-IgG antibodies against GpIIb/IIIa
-antibodies bind platelets and are consumed by splenic macrophages
-high megakaryocytes in bone trying to make more platelets
-give IVIG + splenectomy
Explain immune thrombocytopenia purpura
decreased ADAMTS13 -which cleaves vWF multimers into smaller monomers
Explain Thrombotic thrombocytopenic purpura
PTT does not correct upon mixing normal plasma with patient's plasma due to an inihibitor
How do we compare coagulation factor inhibitor vs hemophilia A
Ristocetin induces platelet agglutination by causing vWF to bind platelet GPIb - no vWF means no agglutination
(Bernard goulier + vWF disease are the two that we see abnormal ristocetin tests on)
Explain ristocetin test
1. decreased production of coagulation factors
2. decreased activation of vitamin K by epoxide reductase
How does liver failure cause abnormal hemostasis (2 ways)?
1. radical prostatectomy - releases urokinase which activates plasmin
2. cirrhosis of liver - reduced production of antiplasmin
2 disorders of fibrinolysis (overactive plasmin)
Cystathionine beta synthase deficiency - high homocysteine levels
-vessel thrombosis, mental retardation, lens dislocation
HIGH LEVELS OF HOMOCYSTEINE CAUSE CLOTTING
- (CBS and lack of vitamin B12 increase homocysteine levels)
Explain cystathionine and increased clotting
Factor 5 requires deactivation by protein C or protein S
in this disease there's no cleavage site for protein C or S to kill factor 5
Explain factor 5 leiden
Hepcidin binds free iron and pushes it into storage sites
-suppresses iron moving in blood
-suppresses erythropoietin production
Explain hepcidin
1. high Ferritin
2. low TIBC
3. low serum iron
4. low % saturation
In anemia of chronic disease:
1. Ferritin?
2. TIBC?
3. serum iron?
4. % saturation?
Aminoevulinate dehydratase (ALAD)
and
Ferrochelatase (mitochondria)
2 enzymes blocked by lead in protoporphyrin synthesis
4 B chains form tetramers (HbH) that damages RBC's
Explain three gene deletions in alpha thalassemia
Decreased haptoglobin (binds the free hemoglobin)
-hemoglobinuria
-hemosiderinuria (kills kidney)
Lab for intravascular hemolysis
IgG = extravascular (SLE is most common cause)
IgM - intravascular
Compare IgG vs IgM hemolytic anemia....what is most common cause of IgG?
Blocks lymphocytes from leaving blood
How does bordetella pertussis cause lymphocytosis?
large immature cells with punched out nucleoli
Explain lymphoBLASTS
TdT+
B-ALL: CD10, CD19, CD20
T-ALL: CD2-CD8
Acute lymphoblastic leukemia markers
Smudge cell - CLL
CD5 and CD20
What leukemia? What 2 lab # positive?
-rash
-hepatosplenomegaly
-punch-ed out lytic lesions with hypercalcemia
Symptoms of Adult T-cell leukemia
Mycosis fungoides - skin rash with plaques
1. Low LAP
2. 9;22
3. basophils
3 ways CML is distinguished from leukemoid reaction
in PV:
EPO levels are decreased
SaO2 is normal
Explain polycythemia vera vs reactive polycythemia
Follicular lymphoma is monoclonal
What is the biggest difference between follicular lymphoma and follicular hyperplasia?
Marginal zone lymphoma
MALToma, Hashimoto thyroiditis, Sjogrens
can all lead to what type of lymphoma?
Nodular sclerosis (Hodgkin Lymphoma)
Enlarging mediastinal lymph node in a young female
Reed sternberg cells are present
IL-6
(infection is most common cause of death in MM because we have monoclonal antibody)
Multiple Myeloma cytokine that stimulates plasma cell growth
1. Temporal arteritis - carotid artery (visual disturbances), jaw claudication, polymyalgia rheumatica
2. Takayasu- pulseless upper extremity (aortic arch)
2 large vessel vasculitis (granulomatous)
fibrinoid necrosis
(Polyarteritis nodosa)
Young girl with melana (black stools), hypertension (renal artery), and neurologic disturbances...what do we see in histology?
1. sinusitis (nose)
2. granulomas
3. C-ANCA (PR3)
(this disease hits nose, kidney, lungs)
3 things specific for Wegener's
Follows URI
1. palpable purpura
2. GI pain and bleeding
3. hematuria
Explain Henoch-Schonlein purpura presentation
Fibromuscular dysplasia
Young woman with hypertension
1. damage to endothelium allows
lipids
to leak into intima
2. lipids are oxidized and consumed by macrophages resulting in foam cells
3. inflammation and healing leads to deposition of ECM and proliferation of smooth muscle
Explain atherosclerosis process
proteins leaking into vessel
-consequence of benign hypertension or diabetes
Explain pathology of hyaline arteriosclerosis
hyperplasia of smooth muscle (malignant hypertension- less than a year or two)
-leads to fibrinoid necrosis of vessel wall with hemorrhage - causes renal failure
Explain pathology of hyperplastic arteriosclerosis
aortic dissection
cystic medial degeneration