Gen Path Review

Lead-induced anemia mechanism

Lead block iron from binding hemoglobin

Result of lead induce anemia

microcytic (small) , hypochromic (RBC not very red) anemia

Factors affecting severity of thermal burns

% body surfacwe involved and depth of the burn (partial or full thickness)

Types of injury radiation can cause

Direct damage to DNA and indirect damage through free radicals

How does radiation cause direct DNA damage cause injury

Directly damages cell's genetic material

How does radiation cause indirect damage

Free radicals damage cell membranes, nucleic acids, and enzymes

Possible outcomes of radiation injury

Reversible cell injury, cell death, fibrosis

Other things radiation may damage

Tissues and organs ex: skin, causing ulcers and edema

Marasmus primary deficiency

Total caloric intake

Kwashiorkor primary deficiency

Protein deficiency

Marasmus appearance

Severe malnutrition, Thin extremeties, head appears disporportionally large

kwashiorkor appearance

Generalized edema

Marasmus serum albumin

Relatively normal or slightly decreased

Kwashiorkor serum albumin

low

Marasmus immune effect

Immune deficiencies, T cell defect, infections common

Kwashiorkor immune effect

Immune system defects, infection common

Marasmus key distinction

Severe calorie deficiency with depletion of muscle and subcutaneous fat

Kwashiorkor key distinction

Greater protein deficiency, depletion of visceral proteins, low albumin, generalized edema

Vitamin A main fxn

Maintains night vision

Vit A deficiency sign

Impaired night vision

Hemostasis

Process that stops bleeding following vascular injury

primary hemostasis

platelet plug formation

steps of primary hemostasis

1. platelet adhesion (vWf) 2. platelet activation (round -> flat with spiky protrustions to inc. SA) 3. platelet aggregation (platelet plug formation)

Secondary hemostasis

Fibrin clot formation

How are coagulation proteins activated

Coagulation pathways/cascade

Regulation of hemostasis is

Mechanisms that prevent excessive clot formation and remove unnecessary clots

What regulates platelet activity

NO, PGI2, ADPase

Antithrombin

inhibits serine proteases involved in coagulation

Protein C and S

Together, inactive factors Va and VIIIa

Fibrinolytic system

Plasmin removes excess fibrin clot

Platelets responsible for

Primary hemostasis and platelet plug formation

Quantitative platelet disorder

abnormal #

Qualitative platelet disorder

abnormal function

T or F: Platelet disorders may be qualitative and quantitative

True

Factor VIII deficiency causes

Hemophilia A

Factor IX deficiency causes

Hemophilia B

PT (prothrombin time) test screens ____ factors

extrinsic + common, fibrinogen

PTT (Partial Thromboplastin Time) test screens ____ factors

intrinsic + common, fibrinogen

Intrinsic coagulation factors

II, V, VIII, IX, XI, XII, fibrinogen

Extrinsic coagulation factors

II, V, VII, X, fibrinogen

How does NO regulate hemostasis?

Regulates platelet activity

How does ADPAse regulate hemostasis?

Regulates platelet activity

INR Test

Standardized PT test used to monitor warfarin

Bleeding time (BT) evaluates

Primary hemostasis

PFA-100 Test screens for

Primary hemostasis

Heparin is monitored using what test?

PTT

Warfarin is monitored using what test?

PT/INR

Hemophilia A symptoms

begin in early childhood, recurrent soft tissue bleeding, hemarthrosis, intramuscular hematomas, excessive bleeding following trauma, intracerebral hemorrhage

How is PTT affected in hemophilia A and why?

Prolonged because factor VIII is intrinsic

How is PT affected in hemophilia A and why?

Normal with isolated factor VIII deficiency (PT tests for extrinsic)

Hemophilia A is caused by what deficiency?

Factor VIII

Hemophilia B is caused by what deficiency?

Factor IX

Symptoms of hemophilia B

Similar to hemophilia A, Soft tissue bleeding, hemarthrosis, excessive bleeding following trauma, Intracranial and retroperitoneal bleeding , Mild cases are difficult to recognize clinically

How is PTT affected in hemophilia B and why?

Prolonged because factor IX is intrinsic

How is PT affected in hemophilia B and why?

Remains normal because PT tests extrinsic and IX is intrinsic

Von Willebrand Disease (vWD)

Autosomal dominant disorder caused by either quantitiave, qualitative, or both abnormalities involving vWF

Clinical reatures of vWD

Mucocutaneous bleeding in skin and mucous membranes

PFA-100 of vWD

prolonged due to abnormal primary hemostasis

PFA-100 screens for

Primary hemostasis

PTT for vWD

May be prolonged if factor VII is reduced

Best way to identify vWD

screen for vWF

Clinical features of platelet disorders

mucocutaneous bleeding, petechiae, excessive bleeding following trauma

Laboratory features of platelet disorders

Prolonged bleeding time, abnormal PFA-100, Thrombocytopenia when platelet count is reduced

Immune thrombocytopenic purpura (ITP)

autoantibodies target platelet membrane antigens

Clinical features of ITP

petechial hemorrhages, gingival bleeding, ecchymoses (bruise), bleeding following trauma or surgery

Thrombotic Thrombocytopenic Purpura (TTP)

Acute disorder characterized by intravascular platelet activation and widespread formation of platelet-rich microthrombi

Cause of TTP

deficiency of ADAMTS13 - supposed to cut vWF multimers

Anemia

Reduction in red cell mass, associated with decreased red blood cell count, hemoglobin and/or hematocrit resulting in impaired tissue oxygenation

clinical signs and symptoms of anemia

shortness of breath, weakness, fatigue, pallor

3 Major mechanisms of anemia

Blood loss, increased RBC destruction, Intrinsic defects

Anemia from acute blood loss

Rapid, more than 20% loss can induce shock

Anemia from chronic blood loss

Loss exceeds RBC generation, causing iron deficiency, leads to anemia

Anemia from RBC destruction (hemolytic anemia)

RBC destroyed faster than replaced. Caused by membrane defects, hemoglobin abnormalities, metabolic defects, immune rxn, mechanical trauma

Intravascular hemolysis

RBC destroyed within blood vessels

Intravascular hemolysis example

Incompatible transfusion, mechanical trauma

Extravascular hemolysis

RBC removed by macrophages, especially in spleen or liver

Extravascular hemolysis examples

hereditary sperocytosis, autoimmune hemolysis, sicklecell disease

Herediatary sperocytosis main defect

spectrin or other structural abnormalities (intrinsic)

Herediatary sperocytosis important findings

spherical, less deformable RBCs, splenic destruction

Sickle cell anemia main defect

Abnormal hemoglobin S

Sickle Cell anemia important findings

Sickled RBCs, hemolysis, microvascular blockage, ischemia, infarction

Thalassemia main defect

Reduced synthesis of alpha or beta globulin chains

thalassemia important findings

Microcytic, hypochromic anemia, basophilic stippling

G6PD deficiency main defect

Reduced protection against oxidative injury

G6PD deficiency important findings

hemolysis following certain drugs, toxins, or infections, bite cells

Iron deficiency anemia pathogensis

Insufficient iron for hemoglobin production

Iron deficiency anemia key findings

Microcytic, hypochromic RBCs, low ferritin

Megaloblastic anemia pathogenesis

Vitamin B12 or folate deficiency impairs DNA synthesis

Megaloblastic anemia Key findings

Increased MCV (big cells), hypersegmented neutrophils, reduced mature RBC production

Pernicious anemia pathogenesis

Autoantibodies against parietal cells and intrinsic factor reduce B12 absorption

Pernicious anemia Key findings

B12 deficiency and hematologic abnormalities

Aplastic anemia pathogenesis

Acquired stem cell defect reduces production of all blood cell types. Often involved T-lymphocyte suppression

Aplastic anemia key findings

pancytopenia and markedly decreased bone marrow cellularity

Myelophthisic anemia pathogenesis

Bone marrow replaced by tumor fibrosis

Myelophthisic anemia key findings

Teardrop shaped RBCs, platelets often decreased

Polycythemia

Increase in red cell mass

Vitamin B12 and or folate deficiency - nutritional anemia mechanism

Impair thymidine production which interferes with DNA synthesis. Cell division is delayed and maturation proceeds as normal leading or large cells (megaloblastic anemia)

Relative polycythemia

Decreased plasma volume

Primary absolute polycythemia

Neoplastic proliferation of RBCs

Secondary absolute polycythemia

increased erythropoietin production