Exam 2: Intro to Clinical Med & Pathology

What do the diseases of the blood vessels and circulatory system affect?

They affect the circulatory system which is the blood vessels and the heart

What kind of diseases are the leading cause of morbidity and mortality, and account for more than one-third of death after birth 

Diseases of blood vessels and the heart

Diseases of the blood vessels and the heart impair the circulation of?

Blood and delivery of oxygen and nutrients (glucose) to tissues/organs (lead to decreased function of cells and organs)

Impaired perfusion

Due to obstruction of blood vessels, rupture of blood vessels, or failure of the heart to pump blood

“Cardiovascular disease (CVD)”

Umbrella term that encompasses disorders of the heart and blood vessels including: Atherosclerotic diseases of the heart or blood vessels (arteries), myocardial infarct, and stroke

What is the most common cause of Cardiovascular disease (CVD)?

Atherosclerosis is the most common cause

What are the major risk factors for diseases of blood vessels and the heart?

Hypertension, diabetes mellitus, hyperlipidemia, and smoking 

Important Disease Conditions of Blood Vessels and Heart

• Atherosclerosis 

• Coronary heart diseases/myocardial infarct 

• Thrombosis 

• Embolism 

• Aneurysms 

• Congenital heart diseases 

• Cardiomyopathy 

• Congestive heart failure

• Hypertension

What are arteries?

 Blood vessels that carry blood away from the heart towards peripheral tissues 

• Arteries normally carry oxygen-rich blood 

What are veins?

Blood vessels that carry blood towards the heart, veins normally carry oxygen poor (deoxygenated) blood 

Pulmonary arteries carry?

Oxygen-poor blood

Pulmonary veins carry?

Oxygen-rich blood 

What is venous blood?

Oxygen-poor blood that flows through the venous system back towards the heart after delivering oxygen to the body’s tissues 

Venus blood turns into?

Arterial blood in the lungs and the blood that comes out through the lungs go through thin pulmonary veins 

To move the blood into the lungs you need?

High pressure

What are the three layers of blood vessels?

Endothelium layer, internal elastic lamina, and the external elastic lamina

Endothelium layer

The intima (made out of endothelium cells, a smooth layer)

Internal elastic lamina

The media

External elastic lamina

The adventitia (or tunica externa)

Major veins of the circulatory system:

Superior vena cava, the inferior vena cava and the medial cubital vein

Superior vena cava

brings blood back from the right arm, collects blood from brain as well

Inferior vena cava

goes through right atrium

Major arteries

Common carotid artery, aorta, femoral artery

The ABC’s of the Aortic Vessels

• A = Aorta

• B = Brachiocephalic trunk splits into right carotid artery right subclavian artery 

• C = Carotid artery (left) 

• S = Subclavian artery (left) 

If the left coronary artery is cut off then?

About ⅔ of the heart muscle will be lost

A lot of myocardial infarcts happen on?

The left side of the heart

Left coronary artery supplies?

 60% of the heart muscle with blood

Edema/effusion

Abnormal accumulation of fluid in interstitial tissues (edema) or in body cavities/spaces (effusion), causes major disturbance in blood flow

Hemorrhage

bleeding, causes major disturbances in blood flow

Thrombosis

Occlusion of blood vessels by local blood clot ( * blood clots can form in the heart), causes major disturbance in blood flow

Venous Thrombosis

Deep venous thrombosis (DVT), causes major disturbance in blood flow

Arterial Thrombosis

Stroke, myocardial infarct, cause major disturbances in blood flow

Embolism

Blockage of a blood vessel by circulating blood clot. Can also be due to fat embolism, air embolism, amniotic fluid embolism. Causes major disturbances in blood flow

Venous Thrombus

(right side of the heart) will end up in the lungs (pulmonary arteries) and lead to pulmonary embolism (cannot go past the pulmonary artery in normal circumstances and cannot go back to the left ventricle because it is too big to fit through), causes major disturbance to blood flow

Arterial Thrombus

(left side of the heart) can result in arterial thrombosis anywhere in the body (ex. stroke) (stuck on the left side of the heart, can reach brain, kidneys, etc.), causes major disturbance in blood flow

Infarction

Tissue necrosis due to occlusion of arterial blood supply leading to tissue ischemia (myocardial infarction, stroke, gangrene), causes major disturbance to blood flow

Shock

Dramatic drop in blood pressure resulting in hypoperfusion of vital tissues (a lack of perfusion of the tissue, affects the whole body), causes major disturbance to blood flow

Edema

excess fluid in interstitial tissues 

• Ex. peripheral edema (arms, legs), pulmonary edema (fluid in the lungs) 

Effusion

excess fluid in a body cavity 

• Ex. pleural effusion (pleural cavity, fluid around the lungs), pericardial effusion (fluid in the sac around the heart), ascites (peritoneal cavity) 

Factors that lead to Edema

Increased hydrostatic pressure, reduced plasma oncotic pressure, lymphatic obstruction, sodium and water retention, inflammation

Increased hydrostatic pressure

Can lead to edema, more fluid is pushed out of blood vessels 

• Ex. heart failure, venous obstruction

Reduced plasma oncotic pressure

Less protein in the blood to retain fluid, can lead to edema

• Ex. kidney disease, liver disease, malnutrition

Lymphatic Obstruction

Impaired drainage of tissue fluid, can lead to edema

Sodium and water retention

increases fluid volume in the body, can lead to edema

What can Inflammation lead to

Increased vascular permeability allows fluid to leak into tissues, can lead to edema

Pitting Edema

It is present when a depression remains upon pressure 

• Edema does not show the cardinal signs of inflammation 

Lymphedemia

It is often “non-pitting” 

• Can be congenital, parasitic, from an infection, etc. 

Ascites

Abnormal buildup of fluid in the abdomen

Caput Medusae

Often due to liver diseases, goes through umbilical veins and skin, makes veins appear swollen and twisted across the abdomen 

75% of the blood flowing through the liver comes from?

The portal vein

Hemorrhage

The loss of blood from the vascular system

• can be acute or chronic

• usually caused by injury or blood vessel rupture

• In healthy adults, blood loss may be tolerated

• severe or rapid blood loss can lead to shock or death

Places where a hemorrhage can occur

Externally, internally, within tissues which forms a hematoma

Factors that affect the severity of hemorrhages

• Volume of blood lost

• Rate of blood loss

• Age 

• Location of the bleeding

How are hemorrhages classified

By size and location

Hemorrhage severity from least to most

Petechiae → Purpura → Ecchymosis 

Petechiae

• Very small, 1-2 mm 

• Hemorrhage in skin, mucous surface 

• Low platelet counts (thrombocytopenia), platelet defects, some milder clotting factor deficiencies, increased blood pressure 

Purpura

• 3mm - 1 cm 

• Same cause as petechiae, vascular inflammation (vasculitis), increased fragility of vessels 

• Can be slightly raised

• Thrombocytopenic purpura, vascular disorders, vasculitis

• Henoch-Schonlein purpura (IgA vasculitis) 

Ecchymosis (bruise)

• >1 cm 

• Bleeding into tissues (subcutaneous), after injury, bleeding disorders 

• Non-blanching purple or red discoloration of skin due to leakage of RBC’s from small ruptured blood vessels

• Cannot be felt 

• Usually not painful or tender

Bleedings in Body Cavities

• Hemothorax (chest cavity)

• hemopericardium (pericard)

• hemoperitoneum (abdomen)

• hemarthrosis (bleeding into joins)

• injury

• bleeding disorders  

Hematoma

• Pocket of blood in tissues

• Hematoma can be felt when touched

• Hematoma can be internal or external

• Often pain or tenderness

Hemostasis

The normal mechanism of how a bleeding is terminated 

Primary Hemostasis

Platelets bind to damaged/inflamed vessel wall and form a platelet plug (occurs in seconds) 

Secondary Hemostasis

Coagulation cascade forms a fibrin clot that stabilizes (“cements”) the platelet plug (may take minutes) 

Thrombosis

The undesired activation of the coagulation system that leads to the occlusion of vessels and hypoperfusion 

The Most Important Factors That Contribute to Blood Coagulation

• Blood platelets

• Platelets

• Coagulation system

Blood Coagulation Sequence of Events

• After injury arteries initially constrict 

• The injury to blood vessels exposes extracellular matrix and tissue factors that activate blood coagulation 

• Platelets adhere to site of injury and become activated and release granules that activate even more platelets 

• Fibrin is produced by the coagulation cascade and stabilizes the platelet thrombus

Coagulation Cascade – The Most Important Step

• Prothrombinase complex: key is activated factor X (Xa) 

• Prothrombin (Factor II) 

• Thrombin → Fibrinogen (Factor I) → Fibrin 

The Coagulation Cascade (13 Factors, I-XIII; no factor VI) 

• Two main coagulation pathways: tissue factor (coagulation factor III) pathway TRIGGERS coagulation, contact activation pathway SUSTAINS COAGULATION

• Coagulation factors are enzymes (several are serine proteases) that catalyze the next reaction of coagulation until fibrin is formed 

• Most important steps: conversion of prothrombin to thrombin, which then converts fibrinogen to fibrin 

The Coagulation Cascade: 1; Tissue Factor Pathway

• “Jump starts” coagulation 

• Primary job is to generate “thrombin burst PT test = prothrombin time 

• PT Test = prothrombin time 

• Reported as INR value for the dosing of warfarin (Coumadin) 

• Note: Warfarin inhibits vitamin K dependent factors (II, VII, IX, X) 

The Coagulation Cascade: 2; Contact Activation Pathway

• Activated by thrombin 

• Also: contact with negative charged surface (bacteria, damaged RBC) activates this pathway

• Tested by the PTT (aPTT) = activated partial thromboplastin time → VIII, IX, XII, XI

• Can be used to measure Heparin effects (Heparin activates antithrombin III) 

• Hemophilia A is the deficiency of factor VIII (90% of hemophilias) 

• Hemophilia B: factor IX 

Hemophilia Lab Tests 

Direct-acting Oral Anticoagulants (DOACs)

• Came on the market first in 2010 incl. Dabigatran (Pradaxa, Boehringer), rivaroxaban (Xarelto, 2011), apixaban (Eliquis 2012) 

• Target thrombin (dabigatran, Pradaxa) or factor Xa (rivaroxaban, Xarelto) 

• As effective as warfarin (Vit. K dependent inhibition of II, VII, IX, X) 

• Much more predictable effects 

• Much faster

• No need for routine anticoagulation monitoring

• Fewer food interactions 

• Problem was lack of antidotes 

• First antidote became available May 2018

Concerns Surrounding DIrect-acting Oral Anticoagulants (DOACs)

• DOACs are 10 to 100-fold more expensive

• Once-a-day dosing may be inefficient and not work for all

• Bleeding risk 

Pathologic Thrombus Formation

• An intravascular blood clot is called a thrombus; the condition is called thrombosis, thrombus = blood clot 

• Thrombi (plural) may form in veins, arteries, or the heart 

• If a thrombus becomes dislodged, it can move with the blood stream until it does not fit through anymore and forms an embolus

Three Main Factors Contribute to Thrombus Formation (“Virchow’s Triad”)

• Stasis of the Blood Flow (creates turbulence)

• Endothelial Injury (atherosclerosis, inflammation, smoking/nicotine)

• Blood Hypercoagulability

Stasis of the Blood Flow that contributes to Thrombus Formation (Virchow’s Triad)

Creates turbulence

• Platelets are forced against vessel walls and in contact with endothelium which may activate them 

• Anti-clotting factors are diluted and endothelial cells activated 

Endothelial Injury that contributes to Thrombus Formation (Virchow’s Triad)

Atherosclerosis, inflammation, smoking/nicotine

• More important for thrombus in the arterial system 

• Exposure of extracellular matrix activates platelets and clotting system 

Blood Hypercoagulability that contributes to Thrombus Formation (Virchow’s Triad)

 Genetic or acquired; elevated prothrombin; autoimmune diseases like SLE can produce antibodies against anti-coagulation factors

Important Risk Factors for Thrombosis/Embolism

• 350,000 to 900,000 cases of DVT per year

• Prolonged bed rest or inactivity 

• Underlying conditions (age + smoking + sitting in the same position)

• Atrial fibrillation

• MI 

• Prosthetic heart valves 

• Status after surgery, fracture, burns 

• Tumors 

Most Important Clinical Situations

• Deep Vein Thrombosis (DVT) 

• Pulmonary Embolism (PE) 

• Arterial Thrombosis 

Clinical Signs/Symptoms of DVT

Swelling, pain, redness

Diagnosis of DVT

• Ultrasound 

• Elevated D-dimers levels (>300 ng/ml) 

• D-dimers are fibrin breakdown products created by plasmin digestive blood clots

• Negative D-dimers basically rule out thrombosis 

DVT Therapy: Anticoagulation

• First line: DOACs or heparin

• Long term: DOACs or warfarin (PT Test) 

• Thrombolysis in extreme situations 

• Inferior vena cava filter (Greenfield filter) in recurrent DVT 

• Prevent by mobilizing patients 

DVT Risk Increased with Superficial Vein Thrombosis

• SVT generally less dangerous than DVT 

• But: SVT can propagate into deep venous system and cause DVT 

• 2-13% severe PE

Varicose Veins (Chronic Venous Insufficiency = CVI) 

• DVT and CVI “travel together” 

• Insufficiency of the venous valves 

• Risk factor for DVT: ~ 4-fold 

• 2-fold increase in PE risk

Pulmonary Embolus – Clinical Picture

• Blood clot from DVT dislodges and ends up in the lungs 

• Major artery in the lungs is occluded: pulmonary trunk, pulmonary arteries

Pulmonary Embolus Clinical

• SUDDEN ONSET of shortness of breath (dyspnea) 

• Rapid breathing (tachypnea) 

• Chest pain

• Cyanosis (blue skin tint) 

• Tachycardia 

• Dizziness, risk factors

Pulmonary Embolus Diagnosis

• Pulse oximetry, chest X-ray (to exclude other conditions) 

• CT scan, CT scan with radiocontrast, pulmonary angiography (contrast X-ray), ventilation-perfusion scan (V/Q scan), ECG, echocardiography, blood tests (D-dimer, clotting status) 

Pulmonary Embolus Treatment

• Thrombolysis (tPA = tissue plasminogen activator; Streptokinase), oxygen, analgesia, anticoagulation, surgical removal of embolus

If a pulmonary embolus is left untreated then?

It has a >25% mortality

Anatomy of a Thrombus

• Alternating bands of pale pink platelets and fibrin (light) with red bands of RBCs (dark) 

• Lines of Zahn mostly form in arteries (fast flowing blood), less often in veins 

• Only form when patient is alive (not post-mortem) 

Arterial Thromboembolism

• Atherosclerosis is the most important cause of arterial thrombosis 

• However, arterial emboli often originate from cardiac thrombi, particularly in atrial fibrillation, valvular heart disease, left ventricular thrombi following myocardial infarction 

• When a thrombus dislodges (embolizes),it enters the arterial circulation and may occlude downstream vessels 

Common Sites of Embolization

• Brain → ischemic stroke

• Kidney → renal infarction

• Lower extremities/skin → acute limb ischemia, gangrene

• Intestine → bowel infarction 

Infarction (Ischemic Necrosis) 

Infarction = ischemic necrosis caused by loss of blood supply 

• Usually due to arterial occlusion >95% of vessel 

• Less commonly due to venous occlusion (venous infarction) 

Anemic (white) Infarct 

• Caused by arterial occlusion

• Occurs in solid organs with end-arterial circulation (heart, kidney, spleen)

Hemorrhagic (red) Infarcts 

• lood enters tissues from collateral vessels or after reperfusion

• Occurs in lungs, intestine, venous infarctions, reperfused infarcts 

Causes: thrombosis, embolus, twisting of vessels, entrapment of a vessel (e.g. in a hernia sac) 

Examples: myocardial infarct, cerebral infarct/stroke, bowel infarction, limb gangrene 

Arterial occlusion usually causes?

White Infarcts

Venous occlusion and reperfusion usually cause?

Red infarcts

Non-Thrombotic Emboli

Fat embolism, air embolism, amniotic fluid embolism

Fat Embolism

• Usually follows fractures of long bones (femur, pelvis) 

• Fat droplets lodge in pulmonary and systemic microvasculature 

• Fat Embolism Syndrome (20-50%), respiratory distress, neurologic symptoms (confusion), petechial rash 

• Classic triad: Dyspnea + confusion + petechiae