Patho Exam 2

Component of Blood

• Leukocytes

• Thrombocytes

• Erythrocytes

• Plasma

All cells derive from…

a single pool of pluripotent stem cells of bone marrow

• 2 Types —> Lymphoid Stem Cells, Myeloid Stem Cells

Erythrocytes

Mature RBCs

Lifespan: 120 days

Characteristics..

• Has biconcave disk → increases surface area to carry more O2 and to squeeze into tight spaces.

• Has Hemoglobin: Carries O2 to body tissues (aerobic metabolism)

• Color: Iron gives red color when oxygenated, blue when deoxygenated

Vitamins and Minerals needed for HGB Synthesis

• Iron

• Folate

• Vitamin B12

Iron

67% of body’s iron is in HGB

• Iron (heme) is recycled → RBC break down in spleen, and heme releases iron and bilirubin. Iron is reused and bilirubin is taken to liver. Bilirubin is conjugated by the liver & put in bile

  • Bilirubin causes jaundice

  • Macrophages bring RBCs to spleen to be broken down

Folate (folic acid)

Needed for DNA & RNA synthesis for RBC production

Vitamin B12

Need for..

• DNA synthesis

• Nuclear maturation

• Normal cell division

• Prevention of myelin breakdown

Erythropoises

Process of red blood cell production in the bone marrow.

Includes..

• Proerythoblasts and Reticulocytes

Proerythroblasts

Produced by pluripotent stem cells in bone marrow

• Precursor cell of RBCs

• Becomes reticulocytes in 1 week

Reticulocyte

Immature RBC made from proerythroblasts that leaves bone marrow, go into circulation, and matures into RBCs with 24-48 hrs

RBC production = Destruction

Balance process of destruction of old RBCs and formation of new RBCs.

• Kidneys sense decrease in O2 and releases erythropoietin to tell bone marrow to make more RBC

Hematocrit (HCT)

Measures mass of RBCs in plasma

Mean Corpuscular Volume (MCV)

Size of RBCs

• Microcytic: Small than normal

• Macrocytic: Larger and floppy

Mean Corpuscular Hemoglobin Concentration (MCHC)

Color of RBCs

• Hypochromic: Discolored and anemic

• Normochromic: Pigmented & typica

Manifestations of Anemia

All anemias due to tissue hypoxia (Low O2 to tissues)

• Anemia: Low RBCs or Low hemoglobin

• Symptoms when HGB >8 :

  • Pallor

  • Fatigue

  • Increase RR (compensatory mechanism to get more O2)

  • CNS responses → Dizziness, fainting, lethargy

Types of Anemia

• Anemia of Acute Blood Loss

• Megaloblastic Anemias → Pernicious Anemia, Folic Acid Anemia

• Iron Deficiency Anemia

• Anemia of Chronic Disease

• Aplastic Anemia

• Hemolytic Anemia

• Sickle Cell Anemia

Anemia of Acute Blood Loss

Rapid blood loss causing a decrease in venous return

• 10-20% loss of blood volume

• Bleeding → Less venus return.

• Lack of stretch is sensed by baroreceptors, which activate compensatory mechanisms and RAAS system

• Low BP and decreased CO & central pressure

  • Blood is diverted to vital organs →Causes kidneys to receive no blood, so it activates RAAS system → Releases renin → Activiates Angiotensin I and II which vasoconstricts → Activates aldosterone which conserves sodium and therefore water to increase blood volume

• Takes 5 days for stem cells to differentirate and RBC count return to normal after 3-4 weeks.

Pernicious Anemia

Vit. B12 (Cobalamin) Deficiency that disrupts coordianted cell division and absence of lipid part of RBCs, leading to myelin break down. 

⭐ L️ack of intrinsic factors (carrier and protector of Vit.B12 as it enters stomach)

• Intrinsic factors released by parietal cells.

Type of Megaloblastic Anemia → Large RBCs due to impaired DNA synthesis. Causes immature cells with sport lifespan.

Cause:

• Gastric disorders

• Terminal Illness 

• Strict Vegetarian Diet

Symptoms:

• Changes in Mucosal cells → Causes sore tongue due to change in cell structure

• Neurologic deficits —> Due to myelin breakdown → Demyelination of spinal cord (Pt. will feel tingling and loss of sensation)

Folic Acid Anemia

Lack of folate which disrupts DNA & RNA synthesis (Thymine and purines needed for cell division) and RBC maturation. 

• Megaloblastic anemia → Increased MCV, normal MCHC

Causes:

• Dietary Deficiency → Folic acid is found in plant sources

• Malabsorption → Body cannot digest or absorb EX: Celiac disease

• Drug interactions

• Pregnancy → Increase blood volume, needs enough folic acid for self and fetus. Needed to prevent neural defects

Iron Deficiency Anemia

Lack of iron in hemoglobin

• Microcytic-hypochromic anemia (small cells that lack color) → Impaired O2 delivery and decreased HGB

Causes:

• Dietary deficiency

• Increased iron demands → Pregnant women or adolescents during growth

• Loss of iron from bleeding

Diagnosis:

• Low iron and ferritin (protein that stores iron) levels

• Low HGB and HCT

• Decreased MCV and MCHC

• Epithelial Atrophy: breakdown of epithelium causes waxy appearance of tongue and brittle nails

Anemia Of Chronic Disease

Results from decreased lifespan & erythropoesis

• Renal failure causes inability to release erythopoient from kidneys to tell bone marrow to make more RBCs.

• T-cell activation and production of cytokines from inflammation blocks erythropoietin response

• Altered Iron metabolism

Diagnosis:

• Normocytic (normal MCV) & Normochromic (normal MCHC)

• Low reticulocyte count → No new RBCs because lack of erythropoietin

• Low transferrin → caused by destruction from cytokines
  
  

Aplastic Anemia

Disorder of pluripotential bone marrow that causes pancytopenia (decrease in RBC, WBCs, and platelets)

Causes:

• High doses of radiotherapy

• Chemicals & toxins that suppress hematopoiesis

• Infections

• Most cases are Idiopathic (unknown cause)

Hemolytic Anemia

Premature destruction/breakdown of RBCs inside the body

Causes:

• Hereditary

• Acquired

Symptoms:

• Easily fatigued, dyspnea, increased RR and depth

• Jaundice → Caused by bilirubin release when RBC breakdown

Diagnosis:

• Normocytic and Normochromic

• Increased Reticulocyte count

• Coombs Test: Diagnosis of immunohemolytic anemias

Sickle Cell Anemia

Inherited Disorder of Abnormal HGB

• Derives from melaria, caused by 2 HbS genes

• HbS polymerizes (combines) when deoxygenated

  • Normal RBCs have glutamic acid, but in sickle cell, it is replaced with valine

  • Valine causes RBCs to collapse when deoxygenated

  • RBCs get trapped in body and causes occlusion (blocking) of vessel

Results in:

• Chronic Hemolytic Anemia → Sickle cell lifespan: 10-20 days

• Blood Vessel occlusion → Causing tissue ischemia (decreased blood supply)

• Pain

Symptoms:

• Stress

• Dehydration

• Physical exertion

• Elevation

Complications

• Vaso-occlusive pain caused by tissue hypoxia

• Acute chest syndrome

• Prone to infections → Spleen atrophies due to repeated occlusions. 

  • Spleen is needed to filter microorganisms in the blood. 

  • Damage to spleen makes Pt more prone to infection

  • May need spleen removed and need pneumoneox injections for life

Polycythemia

Opposite of anemia. Non-malignant disease of pluripotent stem cells in bone marrow causing increased production of blood cells

• Primary: Inherited, caused by mutation of Janus Kinease 2 (JAK-2), which lead to overproduction of RBCs

• Secondary: Acquired, caused by lung diseas,e as RBCs are not oxygenated,  kidneys release more erythopoietin

Diagnosis:

• Increased RBC, HBG &HCT, WBCs, and Platelets

• Decreased iron levels → Can’t carry O2

Complications & Symptoms

• Splenomegaly (Enlarged Spleen) → Need to filter out excessive amount of blood cells

• HTN: Caused by increased cells, which increase blood viscosity

• Increased Viscoisty: Thicker blood. Leads to venous stasis (blood flow slows or stops). 

• Dusky redness to lips, fingernails, & mucous membrane

• Thromboembolism: Blood clot forms & travels, blocking blood flow

• Hemorrage (excessive bleeding): Caused by rapid production of defective platelets

Normal WBC count

4.5-10.5 cell/uL

Leukopenia

Low WBC count

Leukocytosis

High WBC count

Blast cells

Immature, precursor cells

Neutropenia

Low neutrophil count → <1000/uL

• Increases risk of infection

Clinical Manifestations

• Ulcers in mouth and skin lesions

• Recurrent infections

• Fever

Causes:

• Bone marrow disorders

• Leukemia

Treatment

• Meds to increase neutrophil count

• Treat infection till bone marrow recovers

• Giving recombinant human G-CSF (Stimulates growth of neutrophils

Leukemias and Lymphomas

Lymphoid precursors → Pre-B Lymphoblast, Pre-T Lymphoblast

Naive Cell: Small lymphocytic lymphoma

Leukemia

Cancer of blood-forming cells.

• Cells are immature and poorly differentiated

• Cells proliferate rapidly and do not look like parent cells

2 Types:

• Lymphocytic: Involves immature lymphocytes and lymphoid progenitors → Acute Lymphocytic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL)

• Myelogenous: Involves myeloid stem cells of bone marrow → Acute Myelogenous Leukemia (AML) and Chronic Myelogenous Leukemia (CML)

Acute Leukemia

Affects immature blood forming cells. Proliferation of blast cells prevent normal cells from maturing. 

• ALL 

• AML 

Abrupt onset of fatigue, low grade fever, night sweats, & weight loss caused by rapid cell production. 

Characteristics:

• Bone marrow suppression: Causes fatigue, bleeding, & anemia

• Rapid proliferation & Hypermetabolism

• Leukemic infilration: Causes bone pain, lymphadenopathy, splenomegaly, hepatomegaly

• CNS symptoms → Headache & seizures

Acute Lymphocytic Leukemia (ALL)

Unregulated proliferation of B or T-cell Lymphoblast

• Chromosomal changes that affect normal blood cell development

• Affects mostly children

Acute Myelogenous Leukemia

Unregulated proliferation of Myeloid precursor cell of bone marrow

• Caused by acquired genetic alteration → Inhibits myeloid differentiation. Increased blast cell formation

• Affects mostly adults

Chronic Lymphocytic Leukemia (CLL)

Proliferation of more fully differentiated lymphoid cells than in Acute Leukemia. 

• Clonal malignancy of B-lymphocytes → Failure of B-cells to mature to plasma cells (cannot produce antibodies)

• Usually asymptomatic, but with increased infection 

Chronic Myelogenous Leukemia (CML)

Excessive proliferation of marrow granulocytes, erythroid precursors, and megakaryocytes (precursor to platelets)

• Associated with Philadelphia Chromosomes: Translocation of chromosomes that allows unchecked chromosome to proliferate. 

• Expected to see..

  • Anemia

  • Crowded bone marrow

  • Enlarged spleen (splenomegaly)

• Diagnosis: Elevated WBC

Lymphomas

Malignancies of peripheral lymphoid tissues. Solid tumors containing neoplastic lymphoid cells (lymph nodes)

• May be caused by genetic mutation or viral infections

2 types:

• Hodgkins Lymphoma

• Non-Hodgkins Lymphoma

Hodgkin Lymphoma

Mutation of B-cell germinal (where B-cells mature) or post-germinal center of lymph node

• Reed-Sternberg cells are found → Large, abnormal, cancerous tumor cells. Due to inability to remove “bad” B-cells

  • Releases cytokines what lead to inflammation

  • Interspersed among normal lymph tissue and lymph organs → Causes enlarged lymph nodes due to inflammation. Beings in one node and spreads to others.

  • Starts with single node or chain of nodes

Symptoms

• Painless enlargement of lymph node or group of nodes

• Systemic symptoms: Fever, night sweats, itching

• Advanced disease leads to immunologic defect in cell-mediated response → Can lead to fatigue, anemia, and increased risk of infection

Diagnosis:

• Lymph node biopsy

Non-Hodgkins Lymphomas

Lack Reed-Sternberg cells, affect multiple nodes and spread unpredictably. 

• Enlarged lymph nodes in various areas. DOES NOT follow progression like Hodgkins lymphoma. 

Multiple Myeloma

B-lymphocytes become malignant plasma cells.

• Causes osteolytic bone lesions: Leaves holes in bones and causes bone pain

• Bad antibodies or immature antibodies can be detected

• Bad immunoglobulins break down and are toxic to kidneys

  • Will see hypercalcemia and Bence-Jones proteins, which cause pain

  • Plasma cells expand and infiltrate bone marrow

• Cause unknown

Diagnosis:

• Bone marrow aspirate

• Lytic bone lesions

Lab work

• M protein spike serum

• Bence-Jones proteins in urine

Platelets/Thromobocytes

Normal Count: 150K-400K cells/uL

• Remain in blood steam but can be stores in spleen

• Liver and kidneys release thrombopoietin

• 1st step of platelets: Initiate hemostasis

Structural components:

• Granules become mediators when injury to vessel occurs

  • Alpha granules

  • Dense granules: Contain components that make platelets stick together

    • Leads to vasoconstrition at injurt site

• Glycoprotein IIb/IIIA: Connects to fibrinogen and platelets to make bigger plug

• Phospholipids: Binds to calcium in bloodstream & coagulation factors in intrinsic coagulation pathway

Thrombopoietin

Released by liver and kidneys to stimulate megakaryotyces to make more plateletsmegakaryocytes

Megakaryocytes

Precursor platelet cells located in bone marrow

Thrombocytopenia

Low platelet count (<100k cells)

• Increased risk for bleeding → Not enough platelets to make hemostatic platelet plug

  • Spontaneous bleeding may occur when <10k-15k

Causes:

• Bone marrow dysfunction

• Infections

• Excessive platelet destruction → From antiplatelet antibodies

• Massive blood transfusion protocol → Dilutes platelets

• Drug induced

Symptoms:

• Petechiae: Small pinpoint hemorrages on skin

• Purpura: Larger petechiae that can appear purple and can indicate more significant bleeding issues.

Thrombocytosis

High platelet count

• Usually asymptomatic until platelet count over 1 million/uL

• Increased risk for clot formation from platelet adhesion

Causes:

• Primary → Polycythemia vera

• Splenectomy

• Cancer

• Chronic inflammatory disorders → cytokine production

Endothelial Injury:

• Atherosclerosis: Damage to lining of blood vessels. Platelets adhere & release more growth factors to circulation.

• Elevated lipids and cholesterol

• Smoking
  

Blood Clotting Mechanism

Contributes to hemostasis by regulating flow of blood at injury site 

• Creates platelet plug through vasospasm

• Platelet first formed, then hemostatic plug

Hemostasis

Process to stop bleeding through clotting cascade

Step 1: Vessel spasms to reduce flow of blood from rupture (< 1 min).

• Done through thromboxane (TXA2) released by platelets and neural reflexes

Step 2: Formation of a platelet plug to stop bleeding in vessel.

• Done through platelet adhesion as von Willebrand factor (vWf) binds to platelet receptors & collagen fibers.

• Activated platelets release granules.

  • Calcium: needed for coagulation of hemostasis

  • ADP: allows platelets to bind to fibrogen and attract more platelets to increase platelet aggregation

  • TXA2: Attracts more platelets to scene, contributes to platelet plug

Step 3: Blood coagulation to form hemostatic plug (secondary plug)

• Activation of Factor X converts prothrombin into thrombin. Thrombin acts as enzyme to convert fibrinogen into fibrin.

Step 4: Clot retraction through action & myosin in the platelets that act like muscles to squeeze serum out of clot, allowing it to shrink

• Occur 20-60 mins after primary & secondary plugs are formed

Step 5: Clot Dissolution/Fibrinolysis occurs to reestablish blood flow and permanent tissue repair

• Plasminogen, an inactivate precursor to plasmin, is activated by tissue plasminogen activator (tPa, released from injury tissue and vascular endothelium).injured

• TPa cnverts plasminogen into plasmin which acts as an enzyme to digest fibronogen or fibrin, causing clot to dissolve.

Impaired Hemostasis

Caused by Vit. K deficiency or liver disease

Vitamin K deficiency

Vit. K is needed for the synthesis and regulation of clotting factors

• Deficincy in..

  • Prothrombin

  • Factor VII, IX, X

  • Protein C&S

Causes:

• Bulimia

• Parenteral nutrition with antibiotics (feeding tube)

Liver Disease

Leads to diminished production of clotting factors

Defincieny in ..

• Factor VII, IX

• Plasminogen & Alpha 2-antiplasmin

• Clotting regulators → Antithrombin, fibrinogen, protein C&S

• Diminished thrombopoietin → Can’t make new platelets

Triad of Virchow

Risk for developing spontaneous thrombi (formed due to activation of coagulation system)

Causes:

• Injury to the vessel endothelium

  • Plaque

  • Turbulent flow

  • Toxins (bacteria, radiation, chemicals)

• Abnormalities of blood flow

  • Turbulence → damages endothelium, activates platelets & clotting factors, causes thrombi

  • Stasis → Platelets pool next to endothelium and become activated

• Hypercoagulability of blood

  • Primary: Hereditary defects in proteins → Involving hemostasis

  • Secondary: Acquired

Risk Factors for Coronary Artery Disease (CAD)

Major/Non-modifable:

• Advanced Age

• Male & Post menopausal

• Family History

Modifiable:

• Dyslipidemia and atherogenic diet → high fat level in blood caused by high-fat diet

• HTN → injures endothelial wall, activates repair process, and LDL become part of plaque

• Smoking → Causes vasoconstriction and turbulent flow

• Diabetes and insulin resistance → Effects inflammatory response

• Sedentary lifestyle

Atheroscleosis

Plaque bulid up in intimal lining of arteries that prevents blood flow into heart

• Also known as “hardening of arteries” 

• Most common cause of CAD, stroke, and PAD

• Lesions found on heart vessels

  • Can be fixed lesions (stable angina) → Stable plaque that contains hard-covering

  • Unstable lesions (unstable angina) → Thin covering that thins over time, which can rupture. Platelets will adhere to create platelet plug and hemostatic plug which can occlude the vessel

  • MI: Myocardial infarction → STEMI & Non-STEMI

• Heart vessels affected

  • SCA

  • LAD

  • Lef Circumflex

Coronary Heart Disease

2 Types

• Chronic ischemic heart disease: Scarring of heart tissue over time

  • Stable Angina

  • Variant Angina

  • Silent Myocardial Ischemia

• Acute coronary syndrome: Blockage of heart by clot or rupture

  • Unstable Angina

  • Non-ST Elevation Myocardial Infarction (NSTEMI)

  • STEMI

Ischemia

Reduced blood flow in specific body parts

• Seen in T-wave inversion

Stable Angina (CIHD)

Angina Pectoris: Chest pain from fixed obstruction, caused O2 demands being greater than blood flow

• Has a fibrous cap

• Alleviating pain: Pain relief when resting because O2 demands are lower. Pain may radiate to arms

• Warning Signs: Pain at rest → Indicates that angina is changing

Symptoms:

• Pallor

• Sweaty (diaphetic)

• Dyspnea

• Exposure to cold

Variant Angina (CIHD)

Caused by coronary artery spasm (constricton)

• Also known as Prinzmetal angina

• Occurs at rest & nocturnally

• Arrhythmia (abnormal rhythm) risk during attack → Higher risk for sudden death

Acute Coronary Syndrome

• Unstable Angina → Unstable plaque, fibrous cap gone and causes platelet aggregation.

• Non ST-segment Elevation MI → Thrombus sticks to platelets on plaque

• ST-Segment Elevation MI → Thrombus obstructs whole vessel.

Thrombosis & Vessel Occlusion

Cardiac ischemia can occur within 10 sec of vessel occlusion

• Cardiac cells stay viable for 20 mins after death → after, myocytes (cardiac muscles) begin to die.

Process:

1. Atherosclerotic plaque with lipid-rich core and thin fibrous cap.

2. Turbulent flow and other factors cause plaque to rupture

3. Increases inflammation with multiple cytokines, platelet activation and thrombin production.

4. Thrombus forms over lesion and vasoconstriction of vessel

5. Acute decrease in coronary blood flow

6. Causes Unstable angina or myocardial infarction

Biomarkers of Acute Coronary Syndrome

• Troponin

• Myoglobin

Myoglobin

Protein found in myocytes. Myocytes breakdown and fall into bloodsteam. 

Troponin

Regulates calcium & mediates contraction of myocytes

• Detectable ~2-4hrs after onset of MI → Can stay in blood for up to 7days

Unstable Angina

Angina that occurs at rest or is increasing in severity and frequency. Caused by plaque disruption and platelet aggregation

• Reversible myocardial ischemia → small fissure or superficial erosion of plaque. 

• Perfusion returns without necrosis (tissue death) → Blood flow reestablished in 20 mins (see no biomarkers and pain will go away)

• Warning Signs: Plaque is complicated (has no fibrous cap) and MI may occur. 

Non-ST Elevation Myocardial Infarction (Non-STEMI)

Also called subendocardial MI → Does not go through all layers of endocaridum. Thrombus attaches to platelets and plaque causing ischemia, but will be broken down

• Affects only myocaridum (inner layer)

• Normal rhythm of sinus depression

• T-wave inversion → indicated ischemia

• No Q-wave

• Has symptoms of unstable angina → chest pain, dyspnea, pallor

• Infarction causes loss of myocytes, so biomarkers will be seen in blood (myoglobin)

ST-elevated Myocardial Infarction (STEMI)

Is transmural → Goes through all 3 layers of heart, causing lose of function.

• Plaque progresses like unstable angina

  • Thrombus occludes vessel, will not break down and has no blood flow.

  • Causes myocyte necrosis and death

• will see Hyperacute ST elevation or T wave 

Myocardial Infarcton

Damage to heart due to prolonged ischemia. Also known as a heart attack

• Pts usualy die from arrythemia

• When cardio output stops → Baroreceptors kick in and stimulates sympathetic response and RAAS system

Characteristics:

• Abrupt chest pain

• Nausea vomiting

• Fatigue and weakness

• Sympathetic stimulations → due to low cardio output. Causes tachycardia, RAAS system, anxiety

• Skin → Cool, pale, moist

Severe cardiac dysfunction: 

• Leads to shock due to insufficient blood to tissues

• Goes from aerobic to anaerobic metabolism

• Leads to Pulmonary congestion due to blood back up in lungs

• Will heart extra heart sound 

Complications of MI

• Dysrhythmias → Abnormal rhythm (usually v. fib) that causes sudden death

• Heart failure → Lose ability for adequate blood pumping due to tissue damage, clot formation may occur

• Cardiogenic shock

• Throboemboli → Can cause stroke for pulmonary embolism

• Pericarditis

• Mechanical Defects

Pericarditis

Inflammation of pericardium that occurs with larger infarcts that affect contractility

Symptoms:

• Inflammation→ Lose of function, redness, pain

• Friction rub: Sound of scratching when listening to heart, caused by rubbing of membranes

• Types:

  • Acute: Occurs 1st few days of MI. Can also occur due to viral infections, trauma, or renal failure

  • Dressler Syndrome: 1 week to several months of MI. Body sees necrotic myocardium as foreign and creates antibodies against it

Pericardiac Effusion

Fluid accumulation in pericaridum caused by inflammatory response in percarditis, infectous processes, surgery, trauma, or cancer

• Fluid accumulates and compresses heart chambers 

Cardiac tamponade: Extreme case of ventricular squeezing → fluid accumulates around ventricle and preventing it from filling → No cardiac output is life threatening

• Beck’s Triad: HTN w/narrowing pressure pulse, Muffled heart sounds, jugular vein distension (JVD)

  • Elevated central venous pressure prevents blood from returning to R. atriua and R. ventricle, causing fluid accumuation in veins causing JVD and HTN

• Other symptoms → Tachycardia, stimulation of RAAS & SNS

Cardiogenic Shock

Fail to pump blood efficiently to meet body’s demands

• Decreased CO → low BP

• HYPOtension

• HYPOperfusion

• Tissue hypoxia despite adequate intravascular volume - Lack of strech activates conpensatory measures

Compensatory neurohumoral responses → Regulated by baroreceptors

• SNS stimulation

• RAS activation

Manifestations

• Cyanotic

• Low BP

• Low urine output → low blood flow = low perfusion to kidneys

• Neurologic changes → confusion, fainting

Primary Cardiomyopathies

• Hypertrophic Obstructive Cardiomyopathy

• Dilated Cardiomyopathy

Hypertrophic Obstructive Cardiomyopathy

• Most common

• Autosomal dominant disorder

• Myocytes hypertrophy (increased mucle mass in heart_ and cardiac fibrosis (thickienng)

Symptoms → Pain & dyspnea, syncope (fainting)

Arrhythmias → A.Fib, V Fib, V-tach

Dilated Cardiomyopathy

Progressive cardiac dilation and contractile (systolic) dysfunction of ventricles that causes insufficient blood pumping

• Symptoms of heart failure 

• 1/3 cases are hereditary, others are ischemic heart disease

Laminar flow

Streamline and normal flow

• Reduces friction and increases rate of flow

Turbulent Flow

Disrupted and mixed flow. Needs more pressure to drive blood

Systole

Ventricular contractoin

Diastole

Ventricular relaxation

Peripheral Vascular Resistance

Opposition to flow cause by friction between moving components and stationary vessel wall

Afterload

Pressure heart must generate to move blood out of ventricles

Preload

Force load before contraction begins. Amount of blood in ventricles at end of diastole

Supraventricular arrhythmias

Irregular heart rhythm cause by problem in atria

Ventricular arrthymias

Irregular rhythm related to conduction system of ventricles

Chronic Venous Insufficiency

Sustained venous HTN in extremities cause by incompetent veins.

• Can cause outflow obstruction cause by DVT or impaired skeletal pumps (not enough muscles to squeeze blood back to heart)

Signs of Impaired Blood Flow

• Edema → Cause by blood that cannot return to heart. Blood begins to seep into interstitial space

• Hyperpigmentation → RBCs die where blood accumulates, causes brown pigmentation of skin

• Necrosis of SQ fat deposit → Causes skin atrophy 

As disease advances, tissue nutrition impairs:

• Causes Statistic Dermatitis → Thin, shiny, brown skin due to loss of fat deposits, skin becomes fatigue and breaks down

• Causes Venous Ulcers → Causes ulcers when skin is damaged

Triad of Virchow

Risk for developing spontaneous thrombi (blood clots)

• Injury to Vessel Endothelium 

  • Plaques occurs from cholesterol

  • Tuberlulent flow

  • Toxins

• Abnormalities to blood flow

  • Turbluence

  • Venous Stasis → Immobility of extremity allows blood to pool

• Hypercoagulability of blood

  • Primary: Inherited conditions

  • Secondary: Acquired disorders

Deep Vein Thrombosis

Clot forms and lodges into vessel wall and damages wall and triggers inflammatory response

• Leads to accumulation of clotting factors and platelets

Symptoms

• Swelling of foot, ankle, or calf

• Pain and Tenderness -. due to inflammatory response

Complications

• Risk for pulmonary embolism → Can break off and lodge in the lungs

Blood Pressue

BP control is achieved by regulating its determinants

• BP = CO x PVR

  • Cardio Output (CO) → Calculated by stroke volume and heart rate

  • Peripheral vascular resisteance (PVR) → Reflects changes in radius of arterioles and viscosity

    • Baroreceptor sense changes in BP

    • Arterioles constrict or relax

    • Arteries innervated by SNS and PNS pathways

Short Term BP Control Types

• Neural Mechanism

• Humoral Mechanism

Neural Mechanism (Cardiovascular Center)

Regulates temporary imbalance in BP, found in reticular formation of medulla & lower 3rd of pons

Intrinsic reflexes

• Baroreceptor → senses decrease in BP, located in cartoid and aortic vessels

• Chemoreceptors → Vasoconstricts, stimulates by low O2 or high CO2

PNS → Vagus nerve (CN10) slows heart rate

SNS → Increase HR and contractility, vasoconstriction

Humoral (hormones) Mechanism

Regulates BP through secretion of hormones

• RAAS 

  • Renin → persists 30 min-1hr

  • Angiotensin II increases Peripheral vascular resistance → Potent vasoconstrictor, reabsorbs Na in proximal tubules

  • Aldosterone → hold Na which attracts water to increase blood volume.

• Vasopressin (Antidiuretic hormone)→ Released from posterior pituitary gland. Retains water and decrease urine output in kidneys. Secreted in response to decrease BP and blood volume or increased serum osmolarity

• Epinephrine and Norepinephrine

  • Released from adrenal glands.

  • Sympathetic neurotransmitters that increase HR, contractility, & vascular tone

Long Term BP control

Kidneys regulates extracellar fluid (ECF). Regulates BP around equilibrium point

• Increase in ECF → increase BP

  • Pressure diuresis → Increase water secretion

  • Pressure natirutesis → Increase sodium excretion

• Natriuretic peptides help regulate urinary soidum excertion

  • Artial natriuretic peptide (ANP) → Released from cells in R. Atria when atrial pressure increases, causes urine-sodium output.

  • Brain natriuretic peptide (BNP) → Secreted from cells in ventricles. When overstretched, urine-sodium excretion increases.

Hypertension

'“silent killer” 

• Systolic and diastolic readings diagnoses hypertension

  • When checking pt rested for 5 mins and has not smoked or had caffeine within 30 mins

Pathophysiology of Primary HTN

Causes:

• Family History

• Environement/Diet

• Dysfunction of

  • SNS → Increase HR and vasoconstrctions

  • RAAS → Increase Na and H2O retention (increases blood volume)

  • Natruretic Peptides → increase BV and BP

• Inflmmation → smooth muscle contractions

• Obesity → causes changes in adipokines and increase SNS and RAAS

Primary HTN Risk factors

HTN with no cause identified

Non-modifiable

• Family history

• Age → vessels stiffen with age

• Sex (men> under 55, women> after 55)

• Racism

Modifiable risk factor

• High sodium intake

• Obesity

• Alcohol (ETOH)abuse

• smoking

• Diabetes/insulin resistance

• Dyslipidemia (high fat in blood) → Free fatty acids activate SNS response

Secondary

HTN Cause by another disease process (only 5-10% of HTN causes)

Rental HTN Causes

• Renal disease

• Renovascular disease → caused by atherosclerosis of renal arteries

Adrenocortical

• Primary hyperaldosteronism

• Cushing's syndrome

Phenochromocytoma → Tumor of adrenal medulla

Coarctation of Aorta → Increase systolic BP

Cardiovascular Damage in HTN

HTN is the leading risk factor for cardiovascular disorders

• Systolic elevation → Damages heart

  • Causes left ventricular hypertrophy

• Elevated pulse pressues

  • Stretch to arteries causes elastic vessel damage

Kidney Damage from HTN

Nephrosclesis → Progressive damage to vessels & arterioles leading to nephron death.

Brain and Eyes

Slow blood flow and high pressure leads to vision loss

• Stroke

  • Increase BP of nonelastic vessels leading to hemorrhage

  • Ischemic stroke → Caused by plaque accumulation and narrowing of lumen accumulation

• Retinopathy: Damage to eyes

• Dementia

  • Narrowing & sclerosis lead to hypoperfusion → Caused by white matter demyelination

Hypertensive emergency

Systolic: greater than 180

Diastolic: greater than 120

• Damages brain → Arterioles of brain cannot regulate flow of capillary beds, causes fluid in interstital space

• Causes retinal hemorrhage 

• Cardiac ischemia

HTN in Elderly

Caused by stiffened arteries → elastic fibers are replaced by collagen

• occurs in half of ppl 60-69.

• decreased baroreceptor sensitivity

• Increase PVR

• decrease renal blood flow