patho exam 4

vascular constriction (stage 1)

vessel spasm decreases blood flow

vessel spasm constricts vessel and blood flow decreases, platelets release vasoconstrictor

platelet plug (stage 2)

platelets activate, stick to damaged BV, release von wilebrand factor + mediators

fibrin

strands are pulled towards the platelets during clot retraction, this is also digested by plasmin, and if this is in vasculature, it leads to more clots. So: fibrin = more clots, plasmin = less clots

strands that strengthen the blood clot and eventually get dissolved by plasmin

blood coagulation (stage 3)

fibrinogen -> fibrin strands hold clot together

fibrinogen (h2o soluble) -> fibrin strands (h2o insoluble), blood changes from a liquid to a gel

activates factor XII and factor III using extrinsic and intrinsic pathways

intrinsic pathway

slow (1-6 mins), in circulation, factor XII activated

also factors XI, IX, VIII

reinforces clot where vessel is damaged

inside blood vessel wall

begins in circulation

extrinsic pathway

fast (15 secs), exposed tissue, factor III activated by tissue factor

outside blood vessel wall

happens during exposed tissue/trauma

normal hemostasis

blood vessel seals to stop hemorrhage/bleeding -> semisolid clot

abnormal hemostasis

inappropriate/bad blood clots

platelet plug formation

platelets stick to damaged blood vessel wall so they can block off blood flow

blood clot formation

fibrin leads the way to form the blod clot and plasmin leads the way to remove the blood clot.

vessel response to injury (hemostasis)

contracting the vascular smooth muscle to decrease blood flow from the rupture

platelet activity (hemostasis)

the platelets increase activity and platelet count; endothelial cells release vWf -> binds platelet receptors to vessel wall -> platelets release mediators that attract/aggregate platelets

blood clot retraction

clot starts coming back, actin + myosin pulls tg edges of injury + contract, fibrin is pulled towards platelets + squeeze plasma out of clot -> clot shrinks

fibrinolysis (stage 5)

clot dissolution, t-PA activates plasminogen -> releases endothelial cells -> converts plasminogen -> plasmin -> plasmin dissolves fibrin strands and clot dissolves

makes clot stronger

common pathways

activates factor X, last stage of clotting cascade -> makes thrombin + fibrin, makes prothrombin -> thrombin, which makes fibrinogen -> fibrin -> makes thrombus

converges in + extrinisic pathways

clot production

• fibrinogen → fibrin

• fibrin strands pulled tg to make a clot

• factor X → prothrombin → thrombin → stimulates fibrinogen → fibrin

clot breakdown

• plasminogen → plasmin

• fibrin strands pulled tg to squeeze plasma out

• actin + myosin pull fibrin strands tg

• t-PA enzyme activates plasminogen → plasmin -. digests fibrin strands

factor X

Both pathways convert into common pathway

factor I

makes fibrinogen

factor Ia

makes fibrin

factor II

makes prothrombin

factor IIa

makes thrombin

factor IV

makes calcium

factors I - XII

mostly synthesized in liver

vitamin k main function

makes clotting factors

plasminogen

activated by t-PA cells and this converts into plasmin and this is what breaks down the fibrin strands and ultimately breaks up the clot

dissolves fibrin once clot is no longer needed

tissue plasminogen activator (t-PA)

enzyme released by mediators and this is what makes plasmin which breaks down the whole clot.

platelet quantity

amount of platelets there are, and just because the platelet numbers are higher doesn’t necessarily mean that they function properly

platelet quality

how well functioning the thrombocytes are

coagulation factor problems (problems with blood clots)

hemophilia a and von willebrand disease are disorders in which the clotting factors aren’t working properly, which results in mild to moderate bleeding. The point of a clotting factor is to promote blood clots and stop bleeding, so if theres an issue w the factors, then there will be more bleeding than normal

thrombocytopenia

• low platelet count

• <150000 cells/microliter

• high risk of bleeding

• drug induced, malignancies, low immune response, bad platelets in spleen

• treatment: give more platelets

thrombocytopathia

• impaired platelet function

• inhibits TXA2 synthesis for platelets

• using too much aspirin or NSAIDs

• treatment: stops using ASAs and NSAIDs and give more platelets

aspirin effects on platelets

this stops TXA2 → helps w vaso/broncho constriction. If TXA2 promotes platelet function, and aspirin inhibits that, then aspirin will indirectly inhibit platelet function. 

hemophilia a

factor VIII, which helps the intrinisic pathway in reinforcing clots where the vessel is damaged, is deficient due to x-linked recessive disorder

• factor VIII

• affects platelet adhesion + blood clotting

• leads to mild bleeding

factor VIII

works w von willebrand factor to promote clotting + platelet adhesion

if this is deficient → clotting stops + free bleeding increases

von willebrand disease

• defect in von willebrand factor

• affects the binding of platelet receptors to vessel walls (supposed to help platelet adhesion)

• leads to moderate bleeding

widespread clotting + free bleeding

• due to underlying disorder

• complication of malignant neoplasm, endothelial injury, infection → free bleeding + clotting pathway is activated

systemic activation

comes from underlying disorder, not primary disease

complications of clotting for extrinsic pathways

• Obstetric disorders

• Malignant neoplasms

• Systemic infections

• Severe trauma

• burns

complications of clotting for intrinsic pathways

• Endothelial injury

• Infection

• Type 3 hypersensitivity disorder

• Burns

• Hypoxia

• Acidosis

• Shock

• vasculitis

microvascular clot formation

 too much thrombin -> too much fibrin in microvasculature -> fibrin makes mini clots all over

platelet + clotting factor consumption

steps 3 + 5 of homeostasis repeat over and over until all platelets and clotting factors are used up -> patient bleeds and bleeds bc there are no clotting factors to stop blood flow

impaired tissue perfusion (coagulation)

 tissue injury (ex. Look at extrinisic pathway injuries) -> too much thrombin made -> microvasculature + mini clots -> ischemic tissue injury, meaning tissue is injured and no blood is getting to it, all the blood is bleeding out

manifestation of DIC

intense bleeding (hemorhage) and oozing from puncture sites → hypoxia + organ damage

microemboli obstruct blood vessels → impaired tissue perfusion

• perechiae

• oozing

• severe hemorrhage

petechiae (manifestation of DIC)

ruptured capillaries → blemished skin

DIC (disseminated intravascular coagulation) triggers

• obstetric complication

• burns

• severe trauma

→ tissue injury

coagulation keeps occuring at the same time as free bleeding

cause → widespread activation → resource depletion → consequence

severe trauma and burns → coagulation + clotting factors activated → platelets and clotting factors all used up → body cant make more → free bleeding, hemorrhage, petechiae, oozing, hypoxia → tissues aren’t getting enough O2

O2 transport

depends on RBCs and hemoglobin functioning properly

erythropoietin

makes the RBCs

if this is impaired → RBCs cant transport O2 to tissues → poor perfusion

stimulated by low O2 levels

supports O2 delivery

hemoglobin

95% of O2 is bound to this and the heme molecule carries 4 molecules of O2

red bone marrow

erythrocytes form here + stored here

RBCs also travel to liver and stored there

renal erythropoietin

comes from the kidney and signals the bone marrow to start making RBCs. reticulocytes turn into mature erythrocytes.

changes in hemoglobin availability

oxygen is not being delivered to tissues, which can cause tissue hypoxia and decrease functioning. For example, anemia is when there’s a lack of RBCs or low hemoglobin, which means less oxygen delivery to blood.

iron

absorbed by organs (ex. intestine absorbs this nutrient that comes from diet)

this is on hemoglobin + helps O2 get delivered

used for RBC synthesis

unconjugated bilirubin

if this builds up → organs get jaundice

doesn’t support O2 delivery

decrease in Hb or RBC level

not enough iron → tissues dont get oxygen → anemia/hypoxia

doesnt support O2 delivery

low iron levels

hemoglobin (a protein found on red blood cells that actually carries the oxygen) cant be synthesized bc it requires iron to be made. If theres no iron, we don’t have hemoglobin, which means the red blood cells can’t hold the oxygen, which means O2 doesn’t get delivered to tissues.

dietary iron

comes from the foods we eat

• meat

• seafood

• eggs

• poultry

if this is low → chronic blood loss, affects functionality of RBCs → no red blood cells to work with at all → we have to recycle the nutrient we have → cant synthesize new proteins

anemia

• macrocytic/megaloblastic

• microcytic/hypochromic

• normocytic/normochromic

mani: high HR, RR, plasma volume

low iron levels → low Hb → oxygen cant get to tissue → hypoxia → fatigue, weakness, dyspnea

macrocytic/megaloblastic (anemia)

• vitamin B12 + folate deficiency

• big, abnormally shaped RBCs

• normal Hb conc

microcytic/hypochromic (anemia)

• low iron + low Hb

• small RBCs

• pale RBCs in color

normocytic/normochromic (anemia)

• chronic disease

• aplastic or hemolytic

• same size

• issue: not enough RBCs to meet body’s needs

• cause: hemolysis (destruction) of RBCs or low production of RBCs

brain hypoxia

mani of anemia

headache, fatigue, faintness, dim vision

blood redistribution

mani of anemia

pale skin + mucus membranes

vitamin B12

if this is not absorbed → DNA synthesis impaired → RBCs wont get produced

this stops fat + protein metabolism + myelin production in CNS

also maintains existing RBCs, normal cell size and shape, normal functionality

absorbed in small intestine

intrinsic factor

stimulates vitamin B12 production + is secreted by parietal cells

vitamin B12 absorption

 parietal cells secrete intrinsic factor and vitamin b12 gets absorbed in small intestine

DNA synthesis

depends on vitamin B12 absorption → stimulates RBC production → delivers O2 to tissues

megaloblastic changes

vitamin B12/folate deficiency → impairs DNA synthesis → RBCs become abnormally shaped + large → anemia

megaloblastic effects of anemia on CNS

• Brain hypoxia -> headache, faintness, dim vision

• Weakness

• Lethargy

• Ataxia

• parasthesias

iron related pattern

• stimulates Hb production

• stored in liver + bone marrow

• deficiency → microcytic anemia

• low iron → low Hb

• kidney secretes erythropoietin + liver absorbs bilirubin

vitamin B12 pattern

• stimulates DNA synthesis

• intrinsic factor major role → stimulates absorption

• deficiency → macrocytic anemia

• when parietal cells dont secrete intrinsic factor → vitamin B12 doesnt get absorbed in small intestine

• autoimmune destruction or gastric surgery destroys parietal cells

nutritional/absorptive defect effects

will affect more than just the number of red blood cells. It will also affect the oxygen delivery to the tissues and the overall normal functioning of tissues, which results in headache, weakness, and hypoxia. 

aplastic anemia

bone marrow disorder that affects RBCs, WBCs, and platelets

affects ALL THREE cell lines → pancytopenia

dif bw aplastic anemia + other conditions

Aplastic anemia affects all different blood cell lines while other conditions such as hemolytic anemia or macro/microcytic anemia only affect RBCs primarily. Aplastic anemia is also caused by very harsh conditions such as chemo, radiation, and toxins, while the other types of anemias are destruction or abnormalities to red blood cells taht coem from deficiencies of vitamin b12, folate, or iron.

blood loss (anemia)

hemorrhagic anemia, too much blood loss increases risk for hypovolemia -> shock

hemolysis (anemia)

dysfunction, blood transfusion, injury, autoimmune disorder -> premature destruction of RBCs → only affects RBCs

mani: jaundice bc of excess bilirubin

reduced protection (anemia)

low RBCs made in normocytic anemia → not enough RBCs, but Hb and iron levels are fine

mani of iron deficiency

• pallor

• fatigue

• dyspnea

• tachycardia

• dizziness

pancytopenia

impaired bone marrow production → low RBCs, low WBCs, low platelets

mani: anemia, thrombocytopenia, leukopenia

→ anemia from low RBCs, infection risk from low WBCs, bleeding risk from low platelets

altered hemoglobin effects

no Hb → RBCs cant deliver oxygen to tissues

if Hb is polymerized → RBCs change into sickle shape + become more rigid → cant circulate in body correctly

deoxygenation

no O2 getting to tissues or RBCs

hemoglobin s polymerization

this is polymerized inside a deoxygenated RBC → rigid sickle RBC → vessel obstruction → no O2 delivery to tissues → ischemia + hemolysis

sickle cell anemia

mutation in Hb gene → amino acid change (glutamic acid → valine) → abnormal hemoglobin → oxygenated RBC has hemoglobin s → hemoglobin s polymerizes in deoxygenated RBC → rigid + sickle cell shape → RBC sticks to vessel wall + blocks of vessels → ischemia, hemolysis, decreased NO

manifestations of sickle cell anemia

• acute pain

• organ dysfunction

• necrosis

• fatigue

• anemia

• endothelial dysfunction

neutrophil

first part of immune response

first to arrive to injury site + neutralize bacterial infections

if these numbers are low → immune response decreases → body is more susceptible

absolute neutrophil count

total number of neutrophils and this should be more than 1500 microliters

if this is low then this could lead to neutropenia

leukocyte

white blood cell

• granulocyte

• monocyte

• lymphocyte

chain of order

leukocyte → granulocyte → neutrophils, eosinophils, basophils

leukopenia

decrease in number of WBC/leukocytes

most often affects neutrophils

neutropenia

decrease in number of neutrophils

<500 microliters in ANC = severe

severe neutropenia threshold

less than 500 microliters

normal WBC count

5000 - 10000 cells/microliter

normal absolute neutrophil count

1500 cells/microliter

defect in frontline immune response

includes neutrophils, monocytes (→ macrophages), basophils, eosinophils

if these counts are low to begin w → immune response weak → body is more susceptible to disease

congenital neutropenia

• unknown mechanism

• every 21 days, pts have 2-3 days of low neutrophils

severe congenital neutropenia (kostmann syndrome)

• defective gene prematurely destroys neutrophils

• 50% of diagnosed newborns have infection in 1 mo

• infection not always present bc not enough neutrophils to start inflam

• treatment: drugs (filgrastim)

primary autoimmune neutropenia

• antibodies target neutrophil cell membrane antigens

• rare disease in childhood

• benign

secondary autoimmune disease

• antibodies target neutrophil cell membrane antigens

• comes from other autoimmune diseases (ex. lupus, rheumatoid arthritis

infection related neutropenia

• viral, bacterial, parasitic infection → low neutrophil count