BIO-322 Patho Exam 2

CBC

-Complete blood count

-Simple blood draw

-Gives snapshot of blood composition

What are the components of blood?

1. RBC

2. WBC

3. Platelets

4. Hemoglobin

What is excess RBC in circulation called?

Polycythemia

What is a decrease in RBC in circulation called?

Anemia

Anemia

1. Reduction in total # of erythrocytes (RBC’s) in the circulating blood

2. Decrease in quantity or quality of Hb (hemoglobin)

-Both result in a decrease in the oxygen carrying capacity of the blood.

• hypoxemia

• hypoxia

Causes:

1. Impaired erythrocyte (RBC) production

2. Blood loss (acute/chronic)

3. Increased erythrocyte destruction

What are the causes of anemia?

1. Impaired erythrocyte (RBC) production

   1. Decreased or abnormal production

   2. Missing the key ingredients

      1. iron from hemoglobin, folate/B9, B12

      2. All have to get from our diet

   3. Not getting from diet or something wrong in the GI tract so they are not being absorbed

2. Blood loss (acute/chronic)

   1. Acute = lot of blood lost in short amount of time (patient is aware)

   2. Chronic = losing a small amount of RBC over a long period of time (patient may not be aware)

3. Increased erythrocyte destruction

   1. Underlying disease

   2. Sickle cell, thalassemias, etc.

What are the different classifications of anemia?

1. MCV

2. MCH

3. MCHC

4. RDW

1. MCV = mean cell volume

   1. Indication of size of RBC

   2. High MCV = large RBC

2. MCH = mean cell hemoglobin

   1. Amount of hemoglobin per RBC

   2. Can be high in cell that is big (Can change based on the size)

   3. Average mass of hemoglobin per RBC

3. MCHC = mean cell hemoglobin concentration

   1. Average amount of hemoglobin in a given volume

   2. Overall color

   3. How much hemoglobin you have other that entire sample

4. RDW = red cell distribution width

   1. Measures variation in RBC size

   2. Large range = large variability in RBC size

MCV

-Mean cell volume

-Indication of RBC size

-Determines if an anemia is:

1. Microcytic (↓ MCV, small RBC)

2. Normocytic (normal RBC)

3. Macrocytic (↑ MCV, large RBC)

MCH

How much hemoglobin is in a RBC

MCHC

-Determines the overall concentration of hemoglobin in that sample

-Determines if a RBC is:

1. Hypochromic (↓ MCHC, not a lot of hemoglobin, lighter color)

2. Normochromic (MCHC = N, amount of hemoglobin is normal)

What is:

1. Normocytic

2. Microcytic

3. Macrocytic

1. Normocytic = normal RBC size

2. Microcytic = small RBC size

3. Macrocytic = large RBC size

-CBC test = MCV (mean cell volume)

What is:

1. Normochromic

2. Hypochromic

3. Hyperchromic

1. Normochromic = Amount of hemoglobin is proportionate

2. Hypochromic = amount of hemoglobin is too low, RBC is lighter in color

3. Hyperchromic = amount of hemoglobin is too high, RBC is darker in color

-CBC test = MCHC (mean cell hemoglobin concentration)

What determines the color of a RBC?

Hemoglobin concentration

What are the levels of MCV and MCHC in microcytic hypochromic anemia?

↓ MCV

↓ MCHC

What are the levels of MCV and MCHC in macrocyric normochromic anemia?

↑ MCV

normal MCHC

S/S of Anemia

Mild S/S:

1. Fatigue/weakness/dizzy

2. Pallor (skin and mucus membranes) (Pale)

3. Smooth tongue

   1. Beefy red tongue = only in B12 deficiency

4. Cold hands and feet

5. Nail changes (become brittle)

6. Hair loss

Dangerous S/S: (severe anemia)

1. SOB/Dyspnea

2. Chest pain/arrhythmias/tachycardia

   1. Severe lack of O2 = heart beats faster to try to pump more blood and compensate

3. Orthostatic hypertension or syncope

   1. Laying down to standing causes BP to drop

4. Neurological S/S (in B12 deficiency only)

Anemia of Acute Blood Loss

-Rapid onset

-Losing a lot of blood in a short period of time

-Causes:

1. Bleeding (excessively)

   1. Trauma, GI ulcer (lot of them), hemorrhoids, GI bleed

-Hematocrit (Amount of RBC in a sample) is low

• Further decreased by the shift of fluid from interstitial space to blood

  • To try to compensate and increase the blood volume

  • Further dilutes blood

-MCV = normal (RBC size) (normocytic)

-MCHC = normal (hemoglobin amount is normal) (Normochromic

-RBC’s that they have are normal in size and hemoglobin, there are just not very many of them

-Body compensation:

• Lack of RBC reduces amount of O2 in the blood

• Lack of O2 signals to kidneys to make erythropoietin

• Targets RBM and stimulates new RBC production

• Increase in immature RBC

• Makes RDW wider

-↓ hemoglobin

-↓ hematocrit

Anemia of Chronic Blood Loss

-Lose a little bit of blood over a long period of time

-Rate of loss exceeds ability to regenerate

• losing more than you make

-Not only are they losing RBC’s they are losing the iron the body would have recycled

• Iron reserves become depleted

• Iron deficiency occurs

• No iron to make new RBC

-Anemia brought on by chronic blood loss causes iron deficiency

-Microcytic Hypochromic Anemia

-↓ MCV

• small RBC (no iron, cant make hemoglobin, small RBC)

-↓ MCH

• Low amount of hemoglbin per RBC

-↓ MCHC

• Low overall concentration of hemoglobin

Chronic blood loss anemia —> iron deficiency anemia

What type of anemia is microcytic hypochromic Anemia?

-Iron deficiency anemia

-Chronic blood loss anemia

Iron deficiency anemias

-↓ MCV - microcytic

-↓ MCHC - hypochromic

-MC anemia worldwide

-Most common in females from puberty - menopause

-Two main etiologies:

1. Inadequate Iron intake

   1. Dietary lack

   2. Lead poisoning (interferes w/ iron absorption)

   3. Impaired Absorption

      1. Due to GI ailment

      2. Celiac disease, chronic diarrhea, low gastric hydrochloric acid (HCl)

   4. Increased requirements for iron

      1. Growing infant/children/adolescents

      2. Menstruating female

      3. Pregnant female

2. Chronic Blood Loss

   1. Chronic NSAID use

      1. Over the counter anti inflammatory medications

      2. Leading cause of gastric ulcers

      3. Reduce mucus production from stomach

   2. Menorrhagia (heavy menstrual cycles)

   3. Esophageal varices (varicose veins in the esophagus that can rupture)

   4. Pelvic uterine disease (PUD)

   5. Ulcerative colitis

   6. Chrohn’s

   7. GI cancers

   8. Hemorrhoids

   9. Parasitic infections

Iron Deficiency Anemia S/S

-Gradual onset —> can take weeks/months

1. Fatigue, tachycardia, palpitations, tachypnea

2. Pallor (palms, conjunctiva, mucus membranes) (pale)

3. Koionychia (indented nail beds, look smooth)

4. Angular Chelitis (reddening/cracking of corners of the mouth)

5. Alopecia

6. Tongue —> Pale, shiny, smooth

7. Pica —> eating disorder

   1. Craving and eating of non-nutritional substances (ex. ice, dirt, etc.)

What are the CBC values for iron deficiency anemias?

-Everything low except RDW

• ↓ RBC

• ↓ Hb

• ↓ Hct

• ↓ MCV

• ↓ MCH

• ↓ MCHC

Macrocytic Normochromic Anemias

-Megaloblasts (large stem cells) in the bone marrow become unusually large RBC’s (macrocytic RBC’s

• Bigger is not better

• The macrocytic RBC’s die early, leading to anemia

-Abnormally large stem cell gives rise to large RBC

• Abnormally large RBC’s break too soon

• Not a lot of them in circulation

-Causes of megaloblasts:

1. B12 (cobalamin) deficiency

2. B9 (folate) deficiency

3. both obtain through diet

4. missing one or both causes megaloblast to form/ and leads to abnormally large RBC

What are the CBC values in Macrocytic Normochromic anemias?

-↑ MCV

-Normal MCHC

-↑ MCH

Vitamin B9 and B12 deficiencies

-Macrocytic/megaloblastic Anemia

-Both end up with RBC’s that are too big

• Macrocytic (↑ MCV)

• Normochromic (Normal MCHC) (concentration of hemoglobin)

• ↑ MCH (mean cell hemoglobin)

-Large fragile RBC with increased hemoglobin content

• Proportionate to the RBC size

• Not pale in color

• Compared to a normal size RBC, the MCH (mean cell hemoglobin) is high

-RBC is fragile and breaks easily

-↑ MCV (mean cell volume)

-↑ MCH (mean cell hemoglobin)

-Normal MCHC (concentration of hemoglobin)

• Bigger RBC, so hemoglobin is proportionate

Pernicious Anemia

-Macrocytic anemia

-Used to be fatal

-Brought on by intrinsic Factor Deficiency

• Intrinsic factor is made by parietal cells in stomach

• Intrinsic factor binds to B12 to absorb it

• No intrinsic factor = B12 deficiency

-Parietal cells are not making intrinsic factor

-No matter how much B12 you are consuming in your diet, you cannot absorb it.

• Low levels of B12

• Causes macrocytic anemia

-S/S:

1. Smooth and beefy red tongue

2. CNS symptoms - due to nerve demyelination

   1. Paresthesias of fingers and feet (pins and needles)

   2. Difficulty walking (dorsal column pathway)

   3. Weakness, fatigue, dementia?

-Dx:

• Blood:

  • CBC

    • ↑ MCV / ↑ MCH / Normal MCHC

    • Vitamin B12 levels

    • Intrinsic factor

    • Homocysteine levels (↑)

• Figure out the underlying cause

-Tx:

• Vit B12 injections (cobalamin)

  • Bypass the digestive (GI) tract

What other GI disorders can disrupt B12 absoprtion?

-If a person is getting enough B12 in their diet, and making intrinsic factor, they can still end up not absorbing the B12 well

1. If the site of absorption is damaged.

• Celiac disease

• Chrons disease

• These disorders damage the small intestine where absorption of nutrients takes place.

2. Drugs may interfere with B12 absorption

   1. Metformin

   2. Used for managing early T2 diabetes

   3. Can interfere with B12 absorption

Vitamin B9 and B12 in DNA synthesis of the megaloblastic cells

• RBC dna replication process

-Step that requires both B12 and B9 (folate)

• The conversion of homocysteine to methionine

• Need both B12 and folate in RBC DNA replication process

• If we are missing one or other other homocysteine does not get converted to methionine

• Elevated homocysteine in the blood

-If we are missing either of these vitamins, the process stays paused

-Ends up in this unusually large state, and will continue to give rise to cells that are equally enlarged.

If vitamin B12 is low, what is elevated in the blood?

Homocyteine

If vitamin B9 (folate) is low, what is elevated in the blood?

Homocysteine

Functions of B12 and Folate (B9)

1. RBC formation

2. DNA production

   1. Conversion of homocysteine to methionine

   2. No B9or12, RBC dna replication pauses, end up with abnormally large cells.

3. Maintenance of myelin (only B12)

   1. Neurological symptoms

   2. Impairment in nerve conduction and signaling

how do we distinguish if megalobastic anemia is due to B9 or B12 deficiency?

-B12 is also used to maintain the myelin sheath of the axon.

-Could see impairment in nerve conduction and signaling

-Deficiency also causes neurological symptoms.

-Symptoms are dependent on the neurons affected.

1. Numbness

2. Tingling

3. Spastic and flaccid paralysis (muscle spasms or weakness)

4. Paresthesia of fingers and feet

5. Altered mental status

   1. Mania, psychosis, Memory impairment, irritability, depression, personality changes

-With B12 deficiency, the elevated levels of homocysteine are associated with inflammation (pro-inflammatory):

• Increased risk of myocardial infraction and cardiovascular disease

Are there neurological symptoms associated with B9 (folate) deficiency?

No

Folate (folic acid, B9) deficiency anemia

-Results in megaloblastic anemia with the same characteristics as Vit B12, EXCEPT

• NO NEUROLOGICAL CHANGES!!!

- ↑ MCV, ↑ MCH, normal MCHC

-Deficiency usually caused by inadequate intake

-Sources of folate (folic acid)

• Beans, lentils, asparagus, leafy greens (spinach, collards, kale)

-Dx:

• CBC, Folate levels (↓), homocysteine levels (↑)

-Tx:

• Dietary replacement

What happens if there is not enough folate for both the pregnant mother and the developing fetus?

-Spina Bifida

-The neural tube has a defect

• Neural tube forms the CNS including the spinal cord

-Moms who dont get enough folate during pregnancy/ 1st month have a higher risk of that neural tube not developing appropriately.

• Associated with the elevated levels of homocysteine

• Homocysteine impairs the normal development of the fetus’s neural tube and can cause spina bifida

-3 Classifications of spina bifida

1. Mild

   1. neural tube defect prevented the posterior part of the vertebrae from forming appropriately

   2. Lose some protection of the spinal cord

2. Moderate

   1. Spinal column did not form posteriorly

   2. The meningis are protruding out

3. More severe

   1. Meningis are protruding out

   2. Portion of the spinal cord are also protruding out

What are we looking for on a CBC for macrocytic/megaloblastic anemias?

1. ↑ MCV

   1. RBC’s are big

2. ↑ MCH

   1. Because RBC’s are bigger than normal, they look like they have more hemoglobin in them than a regular RBC

3. Normal MCHC

   1. amount of hemoglobin is proportional to cell size

4. ↓ RBC count

   1. Large RBC’s are fragile and break easily, not very many of them

Normocytic Normochromic Anemia

Brought on by acute blood loss

Normocytic Hypochromic / normochromic anemia

Sickle cell

Microcytic Hypochromic anemia

-Iron deficiency anemia

-Chronic blood loss

-Anemia of Chronic disease (chronic kidney disease)

• Kidneys not making erythropoietin

Macrocytic Normochromic Anemia

-B12 deficiency

-Intrinsic factor deficiency

-Folate deficiency

What is the CBC values of macrocytic normochromic anemia?

↑ MCV

↑ MCH

↓ MCHC

What are the CBC values of microcytic hypochromic anemia?

↓ MCV

↓ MCH

↓ MCHC

Sickle Cell Anemia

-Autosomal Recessive Genetic RBC disorder

-Impaired hemoglobin structure

• When O2 binds to hemoglobin, it causes hemoglobin structure to elongate, which causes cells to become a sickled shape

-Causes:

1. Genetic - Autosomal recessive

2. African American

3. Hemoglobin S (sickled) instead of A

4. If you are a carrier for sickle cell, one Hb S and one A, you have protection against malaria

-S/S:

1. Sickling of cells —> Abdominal and bone pain, ulcerations, thrombi, infracts

2. Hemolytic Crisis —> jaundice and hematuria

   1. Increase RBC destruction causes an increase in bilirubin levels

   2. Accumulates in tissues such as eye and skin, makes tissue appear yellow

3. Spleenic sequestrian crisis

4. Aplastic crisis (RBC’s live 10-20 days) (are destroyed faster than the body can keep up with = Anemia)

5. Lack of O2 and hydration increase sickling

-Testing:

• CBC:

  • ↓ Hb, ↑ Hct, ↑ MCHC (hyperchromic), and Howell-Jolly Bodies

    • Because of increase RBC destruction, body is trying to compensate

    • Body makes more RBC

    • Immature cell still has nucleus pieces

    • Unique to sickle cell

• Hemoglobin electrophoresis (HbS)

  • looking for sickled hemoglobin structure

-Tx:

• Antibiotics for underlying infection

• Hydroxyurea

  • Stimulates formation of fetal hemoglobin (HbF)

Normocytic Normochromic Anemia

-Cause: Acute blood loss

-CBC Values:

• MCV = Normal

• MCH = Normal

• MCHC = Normal

• Hb (hemoglobin) = ↓

• RBC count = ↓

-Unique Symptoms: NONE !!

• Just regular anemia symptoms

  • Pallor (pale skin & mucus membranes)

  • Fatigue

  • Compensatory Tachycardia

  • Smooth, pale, and shiny tongue

  • Nail changes (brittle)

  • Hair loss

Macrocytic (megaloblastic) Normochromic Anemia

-Cause: B9 or B12 deficiency, IF deficiency

• No IF, cannot absorb B12, can also cause b12 deficiency

-Unique Symptoms:

• Beefy tongue (red, swollen) (B12 def only)

• **If B12 deficiency** neuro symptoms

-CBC Values:

• MCV = ↑

• MCH = ↑

• MCHC = normal

• RBC count = ↓

Microcytic Hypochromic Anemia

-Causes:

• Chronic blood loss

• Iron deficiency anemia

-Unique Symptoms:

• Spoon-shaped nails (koionychia)

• Pale, smooth, shiny tongue

• PICA (eating non-nutritional things) (ice,dirt)

• Angular Chelitis (reddening of corners of mouth)

-CBC Values:

• MCV = ↓

• MCH = ↓

• MCHC = ↓

• HCT = ↓

• RDW = ↑

Hemostasis

-The arrest of bleeding from a broken blood vessel

-Capillary, venule, and arteriole ruptures are common

• Easily fixed by our bodies through clotting

-Medium and large blood vessel ruptures

• Need external assistance (external pressure, sutures)

What are the three steps of Hemostasis?

1. Vasospasm

   1. Fastest response (immediate)

   2. Vasoconstriction (narrow lumen)

   3. Decreased/slow blood loss

   4. Damaged wall starts to release a bunch of factors including VWF

      1. Helps to form the platelet plug

      2. Activates the platelets

      3. Causing them to stick to each other (aggregation)

      4. Also promotes platelet adhesion (stick to damaged vessel wall)

      5. Forms platelet plug

2. Platelet plug

   1. Temporary patch to slow blood loss

   2. Needs to be reinforced by fibrin

   3. Fibrin is made during coagulation

3. Coagulation Cascade

   1. Get water soluble fibrinogen to insoluble fibrin

      1. Helps stabilize that clot

   2. Extrinsic Pathway (tissue factor)

      1. Outside blood vessel

   3. Intrinsic Pathway (Factor XII, 12)

      1. Inside blood vessel

   4. Common pathway (Factor X, 10)

      1. Intrinsic and Extrinsic working together to form common

What does von Willebrand Factor (vWF) do?

1. Helps to form the platelet plug

2. Activates the platelets

3. Causing them to stick to each other (aggregation)

4. Also promotes platelet adhesion (stick to damaged vessel wall)

5. Forms platelet plug

von Willebrand Factor (vWF)

-Essential for forming a platelet plug

-Released from platelets and damaged endothelial cells

-Binds platelets to platelets (platelet aggregation)

-Activates platelets and allows them to release vWF

-Promote platelet adhesion (stick to damaged wall) creating a temporary plug

Clotting Cascade

-12 clotting factors involved

• They are plasma proteins made in the liver

• Liver failure = cannot clot

-2 pathways

1. Intrinsic Pathway

   1. Starts with factor XII in blood coming into contact with damaged vessel wall collagen fibers

   2. Activates clotting factor XII and triggers series of events

2. Extrinsic Pathway

   1. Damaged tissue releases a protein called tissue factor

   2. Starts a series of reactions

-Both intrinsic and extrinsic can activate clotting factor X (10)

What initiates the extrinsic pathway?

Tissue Factor

Do both pathways become active when a tissue is damaged?

Yes

Intrinsic Pathway

-In blood vessel

1. Exposed collagen in damaged vessel wall activates clotting factor XII (12)

2. Activates clotting factor XI (11)

3. Activates clotting factor IX (9)

4. Activates clotting factor VIII (8)

5. Activates clotting factor X (10)

Extrinsic Pathway

-Outside blood vessel

1. Damaged tissue cells release tissue factor

2. Tissue factor activates factor VII (7)

3. Factor VII (7) then activates factor X

Common Pathway

1. Starts with activated factor X (10)

2. Activated factor X converts prothrombin to thrombin

3. Thrombin converts fibrinogen to fibrin

-FIBRIN IS THE GOAL OF THIS ENTIRE PROCESS !!

What is the test to determine how well the intrinsic pathway is working?

-aPPT

-If factors are insufficient or missing

** ↑ if factors are missing / insufficient **

What is the test to determine how well the extrinsic pathway is working?

-PT test

-How well is the extrinsic pathway running

-If factors are insufficient or missing

** ↓ if factors are missing / insufficient **

What are two genetic disorders that directly affect the intrinsic pathway?

1. Hemophilia A (factor 8 missing)

2. Hemophilia B (factor 9 missing)

-Are not able to run intrinsic pathway well

↑ aPTT

In patients w/ hemophilia, how would their PT test be?

Normal

-aPTT would be high

How does missing/insufficient factors change the time frame for clotting?

Takes longer for the blood to clot, will bleed longer

What is the goal of the clotting cascade?

Fibrin mesh stabilizing the platelet plug

What test measures platelet activation and adhesion? (measures platelet plug)

-BT test

-Deficiency in vWF = ↑ BT test

• Not forming platelet plug well

If a patient has hemophilia B, what will there aPTT, PT, and BT levels be?

• aPTT = ↑

• PT = normal

• BT = normal

What clotting factors does aPTT test the effectiveness of?

1. 12

2. 11

3. 9

4. 8

What clotting factors does PT test the effectiveness of?

1. 7

2. 5

3. 10

4. Prothrombin

5. Fibrinogen

Tissue Factor

-TF = tissue thromboplastin = Factor III

-Stimulates the extrinsic pathway

• Activates factor VII (7)

• Which activates factor X

• When factor X is activated it kicks off the common pathway

-Released into circulation from damaged endothelial cells and tissues

-Stimulates platelet aggregation

What can be triggered if someone has massive amounts of tissue damage?

-DIC

-Disseminated Intravascular Coagulation

How does heparin affect clotting?

-Is released by WBC’s

-Will activate antithrombin 3

• Prevents thrombin from forming

• Which in turn prevents fibrinogen from being converted to fibrin

-Acts as our own natural anticoagulant

What are the two categories of bleeding disorders?

1. Platelet-type bleeding

2. Factor-type bleeding

What is platelet-type bleeding?

-Not making platelet-plug well

-Ex. vWF deficiency or thrombocytopenia (↓ platelets)

• Determine what is causing it by looking at platelet count (vWF D = normal platelet #)

-Testing:

1. ** ↑ BT **

2. aPTT = normal

3. PT = normal

-Superficial bleeding:

1. Nosebleeds, bleeding from gums

2. Purpura (bleeding on skin due to broken blood vessels on skin)

3. Petechia (tiny broken blood vessels

What is Factor-type bleeding?

-Bleeding disorder because of missing or insufficient clotting factors

-Ex. Hemophilia (A/B)

-Bleeding time is fine

-Normal BT = platelet plugs are still effective

-Cannot convert fibrinogen to fibrin

-Deeper bleeding:

• Hemarthrosis (bleeding into our joints)

• Larger pooling of blood deeper into our skin (hematoma)

Hemophilia

-Clotting disorder

-Rare X-linked recessive bleeding disorder

-Certain clotting factors in the blood are missing or insufficient

-3 types:

1. Type A (80%) - clotting factor VIII (8)

2. Type B (15%) - clotting factor IX (9)

   1. Christmas disease

3. Type C (very rare) - clotting factor XI (11)

   1. Autosomal recessive

-S/S:

1. Deeper type bleeding

2. Hematomas

3. Hemarthrosis (joint bleeding)

4. Bleed longer, not faster

-Labs:

• ↑ aPTT

• Normal PT

• Normal BT

• Platelet count is normal

-Treatment:

• Fairly manageable

• Give clotting factors to supplement

Von Willebrand’s Disease

-Are not making platelet plug well

-Autosomal DOMINANT

-↓ vWF or abnormal vWF

-Pathophysiology:

• Platelets are not able to aggregate or adhere to vessel wall

-S/S:

1. Superficial bleeding

2. Nosebleeds, bleeding of the skin or mucus membranes

3. Petechia (very small broken blood vessels)

-Dx:

1. ↑ BT (test)

2. 50% of patient also have a ↑ aPTT

3. If patient has a ↑ aPTT and BT, know that it is not hemophilia

4. Normal PT and platelet count

5. Most accurate test is ristocetin cofactor assay

Fibrinolysis

-Breaking a clot (fibrin strands) apart

1. Platelets slowly release tissue plasminogen activator (tPA)

2. tPA converts inactive plasminogen into active plasmin

3. Plasmin breaks apart fibrin into tiny strands

4. Can measure how much fibrin strands are in a patients blood

-Test to measure how much fibrin has broken down:

• D-Dimer test

-If someone formed a clot inappropriately, their body may attempt to break it down

• If we are unsure of a patients condition, but we think they had a heart attack or stroke, we can run a blood test looking for elevated levels of D-Dimer

• Tell us that patient is attempting to break down clots

• Ex. pulmonary embolism, deep vein thrombosis, stroke, myocardial infarction, DIC

What is DIC ?

Disseminated Intravascular Coagulation

DIC

-Disseminated Intravascular Coagulation

-Does not happen to healthy individuals

• Has to be substantial underlying tissue damage for DIC to occur

-Poor prognosis (life threatening)

-Body goes into a state of hypercoagulation which leads to forming thrombosis (inappropriate clots in an unbroken vessel).

• Start to make lots and lots of clots

• The clots then get carried throughout the blood

• Continue to attract platelets and clotting factors to them

• Getting bigger and bigger and carried further away

• Gets so big it gets stuck

• Blocks blood flow, potentially to vital organs

• Leads to forming thrombosis

• Depletes the amount of clotting factor and platelets in the blood

  • Risk of bleeding out or hemorrhaging

-Hypercoagulation (widespread clotting), clots form thrombosis, leads to ischemia, can block blood flow to multiple organs

-Causes:

• MCC = sepsis

• Cancers

• Major trauma (Massive amount of tissue damage)

• Women who had a C-section (if placenta pieces are left behind)

• Placental abruptions (detaches)

• All the causes cause widespread tissue damage

-S/S:

• no clotting factors or platelets to fix damaged vessel walls

• Hypotension due to hemorrhaging

• Tachycardia

-Testing:

• All abnormal

• ↑ aPPT, PT, BT, fibrinogen, D-dimer

• ↓ platelet count

-If not due to sepsis —> can give heparin to try to break down those clots

What is released for DIC to occur

-Tissue factor

-Gets into blood and triggers widespread clotting

-Not supposed to be in blood, it enters and gets carried away

-Starts attracting other clotting factors to it, widespread clots that continue to grow

-Can eventually block blood vessels leading to ischemic tissue damage

Why does a lack of B9 or B12 cause magaloblasts?

-Does not allow DNA replication to finish

-Cannot convert homocysteine to methionine

• In normal DNA replication it creates two small cells

• If DNA replication does not happen it stays one large cell

What is the MC cause of non-cardiac chest pain?

-GERD

• Heart burn

• Stomach acid in esophagus (regurgitated)

What are some causes of chest pain?

1. Costochondritis (inflammation of cartilage in lungs)

2. Angina Pectoralis

3. Myocardial Infarction

Costochondritis

-Inflammation of the costal cartilage connecting the ribs to the sternum

-Muscular / skeletal chest pain (localized)

-30% of ER chest pain visits

-W > M

-How do you tell its not cardiac?

• Pain in reproducible with taking a deep breath, palpating, touching

-S/S:

• Sharp pain at the connection

  • Gets worse with coughing, deep breathing, or physical activity

  • Can last several months - a year

• Can mimic a heart attack

  • Differences: Can replicate pain w/ palpating, moving, touching

-Causes:

• In most cases = no cause identified

  • Neurogenic, inflammation, muscular imbalance, increased muscular pull on the rib

• May be the result pf physical trauma

  • Direct injury

  • Strenuous lifting

  • Severe bouts of coughing (deep coughing can strain the cartilage)

• Some association w/

  • Scoliosis (one side of cartilage is pulled)

  • Ankylosing spondylitis

  • Rheumatoid Arthritis

  • Osteoarthritis

  • Tumor (benign or cancerous)

-Tx:

• NSAIDS (ibuprofen/acetaminophen)

  • Anti-inflammatory drugs

• Ice

-Heals slow because cartilage does not have a good blood supply

• not very vascular

How do you differentiate costochondritis chest pain with cardiac chest pain?

Costochondritis chest pain is reproducible !!

-Palpate, touch, have the patient take a deep breath

• If it makes it worse

What are the vessels in the heart that are associated w/ angina or MI?

Left and right coronary artery

What has a better prognosis if blocked, R coronary artery or L coronary artery?

-R coronary artery has a better prognosis

-L coronary artery blockage is called the widow maker

Where does the R coronary artery take blood?

Supply blood to R atrium and ventricle

Where does the L coronary artery take blood?

Supply blood to the L side of the heart

What supplies the myocytes of the heart with oxygen?

R and L coronary arteries

Arteriosclerosis

-Thickening and hardening of the blood vessel wall

-MC form is atherosclerosis

Atherosclerosis

-Thee accumulation of foam cells (liquid-filled macrophages) in the arterial wall

• Foam cell buildup = plaque

• Leading cause of coronary artery disease (CAD) and cardiovascular disease (CVD)

-CHRONIC !!

-”Buildup of plaque in the artery”

-Causes wall to become thickened and hard

-CAD = coronary artery disease

• Narrowing of coronary arteries due to atherosclerosis

• Results in acute coronary syndrome

What is coronary artery disease?

CAD = coronary artery disease

• Narrowing of coronary arteries due to atherosclerosis

• Results in acute coronary syndrome

What are risk factors for patients developing artherosclerosis?

1. High fat in diet

2. More LDL and HDL (cholesterol)

3. Hypertension

4. Sedentary lifestyle

5. T2D

6. Age (risk increases w/ age)

7. M > W

What are the modifiable vs. nonmodifiable risk factors for atherosclerosis?

-Non-modifiable

1. Age

2. Gender (M > F)

3. Family history

-Modifiable

1. Smoking

2. HTN (hypertension)

3. DM (diabetes melitis)

4. Sedentary lifestyle

5. Chronic inflammation

6. Obesity

7. High LDL (bad cholesterol)

8. Low HDL (good cholesterol)

9. Anemia (macrocytic normochromic)

   1. hyperhimocysteinemic

   2. Too much homocytsteine in the blood

   3. Inflammatory, can damage the lining of BV

What is your total cholesterol?

LDL + HDL + (20% of triglycerides) = Ttl cholesterol

LDL

-“Bad Cholesterol”

-Transport protein

-Transports cholesterol and triglycerides to different organs and tissues in the body

HDL

-”Good Cholesterol”

-Transport protein

-Removes excess cholesterol from the body and transports it back to the liver to be recycled or disposed of

What are triglycerides?

-Stored form of energy

-Stored in adipose tissue and liver

How does plaque progress in the walls of arteries?

1. Has to be underlying damage to the wall of the artery

   1. Risk factors

2. Macrophages can get into the wall of the artery and start to consume fat

3. Developing foam cells

4. They then get stuck in the wall of the artery

5. Causing whats know as the fatty streak

6. Body tries to heal itself

7. Fibroblasts will start to lay down collagen fibers

8. Creating a dense cap over the foam cells

9. Further contributing to the thickening of the artery wall

10. Creates fibrous plaque (prone to injury)

11. If fibrous plaque gets damaged it exposes the collagen fibers into the blood

12. Clotting factors in the blood are activated (factor XII)

13. Clotting factors don’t see it any different then if the blood vessel wall was damaged

14. Triggers a clot (coagulation)

15. As a clot develops, the blood vessel lumen decreases even more

How much of the coronary artery has to be blocked (occlusion) for symptoms to show?

-More than 50%

-Won’t show symptoms until over 50% is blocked

-Systematic w/ increase myocardial oxygen demand

-Asymptomatic at rest

• Even if over 50% blocked, may not show symptoms at rest

What kind of angina is stable plaque?

-Stable angina

-Collagen plaque (cap) is not cracking