Most common symptom = pain
HEMODYNAMIC DYSFUNCTION
HEMODYNAMIC DYSFUNCTION
Edema
Abnormal accumulation of fluid in the interstitial spaces or body cavities
Edema due to hemodynamic dysfunction may result in the brain, lung, subcutaneous tissue, peritoneal cavity
NOT the pancreas
May result from:
Increased capillary permeability (principal factor)
Elevated capillary pressure
Increased interstitial fluid colloid osmotic pressure
Decreased plasma colloid osmotic pressure
Increased sodium retention
Increased venule blood pressure
Lymphatic obstruction
Types of edema:
Anasarca – Can’t see your Sarcs (Muscles because you’re so swollen)
• generalized swelling or massive edema; generalized infiltration of edema fluid into subcutaneous CT
• NOT usually associated with CHF
Hydrothorax – excess serous fluid in the pleural cavity
• Usually from cardiac failure
Hydropericardium – excess watery fluid in the pericardial cavity
Ascities (hydroperitoneum) – excess serous fluid in the peritoneal cavity
Transudate – noninflammatory edema fluid resulting from altered intravascular hydrostatic or osmotic pressure
Exudate – inflammatory edema fluid from increased vascular permeability
Right sided CHF leads to peripheral edema
Most conspicuous clinical sign of right sided heart failure
Left-sided CHF leads to pulmonary edema
Edema may described as:
1) Pitting edema – press against swollen area for 5 sec, then quickly remove it – indentation left that fills slowly
2) Nonpitting edema – press against swollen area for 5 sec, then quickly remove it – no indentation left in skin
Thrombus:
Solid mass of clotted blood that develops in & is attached to a BV wall
Formation enhanced by endothelial injury, alteration in blood flow (turbulence), & hypercoagulability
Arterial thrombi show alternating red & white laminations (lines of Zahn)
Venous thrombi are more uniformly red w/ distinct lines
Conditions predisposing to venous thrombosis:
• Heart failure, extensive tissue damage, bed rest, pregnancy, oral contraceptives, age, obesity, & smoking, Just had surgery, bound to wheelchair, cirrhosis/Increased Portal HTN
♦ Except COPD
A whole thrombus may detach to form a large embolus or fragments may break off to generate small emboli
Different types of Thrombi:
Agonal – forms in heart during the dying process after prolonged heart failure
Mural –
• forms as a result of damage to ventricular endocardium (usually left ventricle, following myocardial infarct)
• A major complication is a cerebral embolism
• It complicates myocardial infarctions, atrial fibrillation, & atherosclerosis of the aorta
White – composed chiefly of blood platelets
Red – rapidly forms by coagulation of stagnating blood – composed of RBCs rather than platelets
Fibrin – formed by repeated deposits of fibrin from circulating blood – usually does not completely occlude the vessels
Ten days after hospitalization for a large, incapacitating myocardial infarct, a 50-year-old man suddenly develops paralysis of the right side of his body. The best explanation for his brain damage is…detachment of a mural thrombus from the left ventricle
Stoke following MI is caused by arterial thrombi (not venous)
Thrombosis:
Formation or presence of a blood clot inside a blood vessel or cavity of the heart
Deep Vein Thrombosis
Predisposed by Virchow’s triad
• Stasis, Hypercoagulability, and Endothelial damage
Thrombotic occlusion in a coronary artery may result in:
Infarction
Fibrosis
Conductive changes
Nothing
Thrombolysis:
Breaking up of a blood clot
Embolus:
Blood clot that moves through the bloodstream until it lodges in a narrowed vessel and blocks circulation
Mass of solid, liquid, or gas that moves w/in a BV to lodge at a site distant from its origin
Most emboli are thromboemboli
Can lodge in the vascular beds of vital organs, occluding blood flow & possibly causing infarction
Splenic infarcts most commonly result from emboli originating in the left side of the heart
56-yr-old with atrial fibrillation and hx of MI 2 yrs ago, experiences a right flank pain and hematuria, paralysis of the right side of the body and ischemia to the left foot
DUE to arterial emboli (NOT septicemia, venous thrombi or venous emboli)
A pt w/ cardiovascular disease has chronic atrial fibrillation. She is prescribed warfarin (Coumadin) to prevent stroke
Think FAT BAT Fat, Air, Thrombus, Bacteria, Amniotic fluid, Tumor
Fat embolism
Associated w/ long bone fractures
More info found elsewhere in file
Air Pulmonary thromboembolus = pulmonary embolus
Very common occurrence
Occurs during times of venous stasis (prolonged bed rest or sitting, CHF)
Most common source of a pulmonary embolism is thrombophlebitis (a thrombus formed w/in a vein)
95% of pulmonary embolus come from Deep Leg Veins
• In this case, a deep leg vein is the common source for the origination of the thrombus
• A thrombotic embolus originating in the femoral vein usually becomes arrested in the pulmonary circulation
Saddle Embolus:
• A large embolus that may occlude the bifurcation of the main pulmonary artery
• Usually results in sudden death
Symptoms:
• Sudden shortness of breath, tachycardia, hyperventilation, cardiognenic shock
May result in:
• Atelectasias
• Cardiogenic shock
• Pulmonary hemorrhage
• Pulmonary HTN
♦ NOT absence of symptoms
Diagnosis:
• Ventilation/perfusion scan
Amniotic Fluid embolus
Can lead to DIC, especially postpartum
Atheroslcerotic Brain Infarction
Most likely warning sign of impending brain infarction is transient ischemic attacks
So, here’s the story on TIAs:
TIAs are caused by a temporary disturbance of blood supply to a restricted portion of the brain
TIAs are called mini strokes, because their neurological symptoms last < 24 hours
TIAs are often called a warning sign for an approaching cerebrovascular accident, or “stroke”
• Strokes last > 24 hours
The most common cause of a TIA is an embolus, which most frequently arises from an atherosclerotic plaque OR from a thrombus
Phlebitis:
Inflammation of a vein
Pylephlebitis:
Inflammation of portal vein or any branches
Congestion:
Accumulation of excessive blood w/in BVs
Shock:
Set of hemodynamic changes reducing blood flow below a level providing adequate O2 for metabolic needs of organs/ tissues
Requires immediate medical Tx – can worsen very rapidly
Clinical signs:
Reduced cardiac output is the main factor in all types of shock
Tachycardia, hypotension, pallor, diminished urinary output, & muscular weakness
Anoxia most severly affects brain & heart
The body produces excess acid in the advanced stages of shock, when lactic acid is formed through the metabolism of sugar
Major classes of shock:
Hypovolemic
• Produced by a reduction of blood volume
• Causes include hemorrhage, dehydration, vomiting, diarrhea, & fluid loss from burns
Cardiogenic
• Due to the sudden reduction of cardiac output
• Main cause is myocardial infarction
Septic
• Due to severe infection
• Most frequently caused by endotoxins from G- bacteria!!!!!
Minor classes of shock:
Neurogenic
• Results from injury to the CNS
Anaphylactic
• Shock that occurs w/ severe allergic reactions
Stages of shock:
1) Non-progressive (early)
• Compensatory mechanisms maintain perfusion of vital organs (↑ HR & ↑ peripheral resistance)
2) Progressive
• Metabolic acidosis occurs (compensatory mechanisms are no longer adequate)
3) Irreversible
• Organ damage – survival not possible
Tx:
Epinephrine is the drug of choice
Amoxicillin Rxn
Pt becomes hypotensive, itchy, and having difficult breathing
• This means Amox reacts with IgE and activates cytotoxic T cells that release lymphokines BLOOD DISORDERS
Purpura spots:
Purplish discolorations in the skin produced by small bleeding BVs near skin surface
Petechiae = small purpura spots, small pinpoint hemorrhages
Ecchymoses = large purpura spots
Both ecchymosis & purpura are manifestations of hemorrhage
May also occur in the mucous MBs (e.g., lining of mouth) & in internal organs
By itself is only a sign of other underlying causes of bleeding
May occur w/ either normal platelet counts or decreased platelet counts
Kinds of Purpura:
Thrombocytopenic Purpura (Werlhof’s disease):
• Autoimmune disorder
• Bleeding disorder characterized by deficiency in platelet #
• Results in multiple bruises, petechiae, & hemorrhage into the tissues
Thrombotic Thrombocytopenic Purpura (TTP):
• Severe & frequently fatal form characterized by low blood platelet count
• Due to consumption of platelets by thrombosis in terminal arterioles & capillaries of many organs
Melena:
Presence of dark, tarry stools, due to the presence of blood altered by the intestinal juices
Refers to digested blood in the stool – a manifestation of hemorrhage
BLEEDING/CLOTTING DISRODERS:
Laboratory values:
PT = prothrombin time
• Measures Factors I, II, V, VII, X
PTT = partial thromboplastin time
• Measures Factor XII, prekallikren, kininogen, Factors I, II, V, VII, IX, X, XI
TT = thrombin time
• Measures Factor I
Clotting/Clot lysis
Process:
• Prothrombin converted to thrombin (in presence of thromboplastin & calcium ions)
♦ Thromboplastin is released by damaged cells, thereby initiating the formation of fibrin
♦ Prothrombin is produced in the liver with help from Vitamin K
• Thrombin in turn converts fibrinogen to fibrin
• Fibrin threads then entrap blood cells, platelets, & plasma to form a blood clot
Fibrinogen:
• Plasma protein that is essential for the coagulation of blood and is converted to fibrin by thrombin & ionized calcium
• NOT in serum
Fibrin:
• Stringy, insoluble protein responsible for the semisolid character of blood clot
• Serves as a template for fibroblasts to repair tissue & walls of the area to infection
• The product of the action of thrombin on fibrinogen in the clotting process
Plasminogen:
• Inactive precursor to plasmin that is present in tissues, body fluids, circulating blood, & w/in clots
• Converted by Steptokinase, Staphylokinase, and Urokinase
Fibrinolysin = Plasmin:
• A proteolytic enzyme derived from plasminogen
• Essential in blood clot dissolution
• Not a component of the body’s nonspecific disease mechanism
♦ Lysozyme, complement, interferon & properdin ARE components of the body’s nonspecific disease mechanism
• The most important fibrinolytic protease
Fibrinolysis:
• Restores blood flow in the vessels occluded by a thrombus and facilitates healing after inflammation and injury
Aspirin
Marked with normal clotting time and normal platelet count, but prolonged bleeding time
It just inactivates them, meaning they are still there, but don’t work
Factors causing delayed blood clotting:
**Pt taking Heparin (anticoagulant) – acts as an antithrombin by preventing platelet agglutination
• Heparin is found in the blood
**Pt w/ leukemia – often has thrombocytopenia (reduced # of platelets)
• Spontaneous gingival bleeding with leukemia
**Pts w/ cirrhosis – have hypoprothrombinemia (abnormally small smounts of prothrombin in circulation)
• In pts w/ liver disorders, it is difficult to curb hemorrhage due to hypoprothrombinemia
• Prothrobmin is formed & stored in parenchymal cells of liver
• In cirrhosis, these cells are profusely damaged
• Pts w/ severe liver disease may have hemorrhages due to a deficiency in prothrombin
**Scurvy
**Thrombocytopenia:
• Condition in which there is a reduced number of platelets
• Causes bleeding states wherein blood loss occurs through capillaries & other small vessels
• Most common cause of bleeding disorders
• Causes spontaneous bleeding
• Most common sign is petechiae and purpura
• Platelet count must reach a very low value (15,000 – 20,000/mm) before generalized bleeding occurs
• Is the cause of prolonged bleeding time in pts w/ leukemia
• Bleeding time increases but neither PT or PTT are affected (bc thrombin and thromboplastin and all the factors they measure (1,2,5,7,10…) are unaffected)
♦ They don’t change because they measure FACTORS, not platelets
**Von Willebrand’s disease:
• Characterized by spontaneous bleeding from mucous MBs & excessive bleeding following trauma
• Deficiency of vWf resulting in impaired platelet adhesion (although there’s nothing wrong w/ the platelets)
• Autosomal dominant bleeding disorder – equal frequency in both sexes
• Prolonged bleeding time; Normal platelet count & PT; Prolonged PTT
• Results in a functional Factor VIII deficiency, because vWf serves as a carrier for factor VIII (hence prolonged PTT)
**Long-term ASA (cyclooxygenase inhibitor) Tx
• Rsults in impaired thromboxane production (important platelet aggregants)
**Dicumarol:
• An anticoagulant that inhibits formation of prothrombin in liver
• Interferes w/ metabolism of Vit K (needed for prothrombin synthesis)
• Used to delay blood clotting especially in preventing & treating thromboembolic disease
• Has largely been replaced by Warfarin
**Bernard-Soulier disease – hereditary platelet adhesion disorder
**Glanzmann’s thombasthenia – defect of platelet aggregation
Hemophilia:
Hereditary bleeding disorder causing 1) increase in clotting time & 2) abnormal bleeding
• Normal PT (Prothrombin time) but Prolonged PTT (Partial Thromboplastin Time)
Hemophilia A & B are inherited as a sex-linked recessive trait
• Males are affected & females are carriers
• Majority of people have type A & it presents under age 25
Excessive bleeding form minor cuts, epistaxis, hematomas, & hemarthroses
Classifications of hemophilia:
• A – classical type – deficiency of coagulation factor VIII (antihemophilic factor)
♦ 10 yr old boy dies post tooth extraction. He also had bleeding into his joints, especially his knees, maternal uncle and male cousin had similar experience
• B (Christmas disease) – deficiency of factor IX (plasma thromboplastin component)
• C (Rosenthal’s syndrome) – not sex-linked, less severe bleeding – deficiency of factor XI (plasma thromboplastin antecedent)
True hemophiliac is characterized by:
• Prolonged partial thromboplastin time (PTT) – because it measures Intrinsic Pathway 12-11-9-10
• Normal prothrombin time (PT)
• Normal bleeding time
HYPERTENSION:
Usually has no symptoms at all (called the silent killer) – millions of people w/ high BP don’t even know they have it
Factors age, obesity, DM, smoking, genetics, race (black > white > asian)
Predisposes to Coronary heart disease, CVA, CHF, renal failure, and aortic dissection
Pathology Hyaline thickening and atherosclerosis
The following may be evident:
Tiredness, confusion, visual changes, nausea, vomiting, anxiety, perspiration, pale skin, or an angina-like pain
Hypertensive heart disease is usually associated with left ventricular hypertrophy as an anatomic finding
Organs damaged due to prolonged HTN:
Heart – 60% die of complications
Kidneys – 25% die to complications
Brain – 15% die of complications
Essential HTN:
High BP from no identifiable cause
Accounts for 90-95% of HTN cases (related to increased CO or increased TPR)
If left untreated can lead to retinal changes, left ventricular hypertrophy, & cardiac failure
Genetic factors include family Hx of HTN – more common & usually more severe in blacks
Benign Nephrosclerosis is the most common autopsy find of essential HTN
Environmental factors – stress, obesity, cigarette smoking & physical inactivity
Secondary HTN:
Kidney failure = most common cause
Others causes: Obstructive sleep apnea, Aldosteronism, Renal artery bruits (suggests renal artery stenosis)
• If renal artery is occluded, you get secondary HTN – kidney thinks blood volume is low, so tries to compensate and you get HTN.
Others causes still: Renal parenchymal disease, Excess catecholamines, Coarctation of the aorta, Cushing’s syndrome
Even more other causes: Drugs, Diet, Excess erythropoietin, Endocrine disorders Findings in HTN
Findings Basis of findings
Cardiovascular
BP persistently >140/90 Constricted arterioles – cause abnormal resistance to blood flow
Angina pain Insufficient blood flow to coronary vasculature
Dyspnea on exertion Left-sided heart failure
Edema of extremities Right-sided heart failure
Intermittent claudication Decrease in blood supply from peripheral vessels to legs Neurologic
Severe occipital headaches w/ nausea & vomiting;
drowsiness, giddiness; anxiety; mental impairment
Vessel damage w/in brain, characteristic of severe HTN Renal
Polyuria; nocturin; diminished ability to concentrate urine; protein & RBCs in urine
Arteriolar nephrosclerosis (hardening of arterioles w/in kidney) 25% die of renal failure
Ocular
Retinal hemorrhage & exudates Damage to arterioles that supply retina
Preeclampsia (Pregnancy-Induced HTN)
Triad HTN, proteinuria, and Edema
When seizures are added, its called Eclampsia
Affects 7% of pregnant women from 20 weeks gestation to 6 weeks postpartum
Increased incidence in pts with preexisting HTN, DM, Chronic renal disease, and autoimmune disorder
Can be associated with HELLP Hemolysis, Elevated LFTs, Low Platelets
Clinical features Headache, blurred vision, abdominal pain, edema of face and extremities, altered mentation, hyperreflexia,
Tx Deliver fetus ASAP
ANEMIA:
Condition in which # of RBCs is lower than normal
Measured by a decrease in hemoglobin
Body gets less O2 & therefore less energy than it needs
Symptoms – fatigue, weakness, inability to exercise, & lightheadedness
Megaloblastic anemia:
Any anemia usually caused by deficiency of vitamin B12 or folic acid
• Deficiency in Folic acid is most common
Characterized by macrocytic erythrocytes (same as below under macrocytic)
Includes pernicious anemia & anemias caused by folic acid deficiency (sprue & megaloblastic anemia of pregnancy)
Pernicious anemia:
• Caused by lack of intrinsic factor (needed to absorb Vit B12 from GI tract)
♦ Vit B12 is necessary for formation of RBCs
♦ Vit B12 also needed to help by nerve cells function properly
♦ Best Tx with Vit B12
• Causes a wide variety of symptoms – fatigue, SOB, tingling sensation, difficulty walking & diarrhea
• Characteristics –
♦ Reduction in acid secretion by the stomach
♦ An increased tendency toward gastric carcinoma
♦ Atrophic glossitis
♦ Myelin degeneration in the spinal cord
♦ Easy fatigability
♦ Peripheral neuropathy
NOT Microcytic or hypochromic
• A type of megaloblastic anemia
• Erythrocytes produced are macrocytic & appear hyperchromic
• Atrophic glossitis AND Atrophic gastritis is common
Aplastic anemia:
Result of inadequate erythrocyte production – due to inhibition or destruction of red bone marrow
• A stem cell defect, leading to pancytopenia
Results from drug-induced bone marrow suppression
Can be caused by radiation, various toxins, & certain medications
• In drug-induced aplastic anemias:
♦ RBCs appear normochromic (normal [hemoglobin]) & normocytic (normal size)
♦ Just Few in #
Pancytopenia characterizd by severe anemia, neutropenia, and thrombocytopenia caused by failure or destruction of multipotent myeloid stem cells, w/ inadequate production of differentiated lines
Tx: withdrawal of offending agent, allogenic bone marrow transplant, RBC & platelet transfusion w/ G-CSF & GM-CSF
Hemolytic anemias:
Anemias due to shortening of RBC life span (↑ RBC destruction)
Problems often result from the subsequent increase in bilirubin levels (breakdown product of hemoglobin)
• Elevated levels of urobilinogen (compound formed in intestine by reduction of bilirubin)
• Elevated kernicterus – Jaundice of the KERNAL – your head
• Elevated levels of unconjugated bilirubin (water-insoluble bilirubin)
♦ Unconjugated bilirubin normally combines w/ serum albumin in the liver to become water-soluble (conjugated)
Conjugated bilirubin is then secreted w/ other bile components into the small intestine
Kernicterus = toxic accumulation of unconjugated bilirubin in the brain & spinal cord
EXs of hemolytic anemia: 1) Erythroblastosis fetalis, 2) Sickle cell anemia, 3) Thalassemias, 4) Hereditary spherocytosis
• By the way, these are all red cell disorders
1) Erythroblastosis fetalis:
• Not an autoimmune Disease
• Fetus is Rh-positive because the father passed along the dominant trait
• Mother is Rh-negative & responds to the incompatible blood by producing Ab/s against it
♦ High risk = Dad is Rh-positive and Mom is Rh-negative
♦ In a case of Erythrblastosis fetalis, the mother has very high levels of serum complement and anti-Rh IgE
• Antibodies cross placenta into fetus’ circulation, where they attach to & destroy the fetus’ RBC – leads to anemia
• Can also result from blood type incompatibilities (i.e., mother may be type O & fetus may be type A or B)
2) Sickle Cell anemia:
• Caused by Hemoglobin S – an abnormal type of hemoglobin
• Autosomal recessive
♦ Heterozygous get the trait
♦ Homozygous get the disease (You know Homos are bad)
So if pt homozygous, bad
• Globin portion of Hb S is abnormal – valine is substituted for glutamic acid in the 6th position of Hb molecule
♦ Valine replacing glutamic acid is a MISSENSE mutation – base substitution leading to different AA
• When Hb molecules are exposed to low [O2], they form fibrous precipitates w/ the erythrocytes
♦ This distorts the RBCs into a sickle (crescent) shape
♦ Sickle cells function abnormally & cause microvascular occlusion & hemolysis
The clots give rise to recurrent painful episodes called “sickle cell pain crisis”
• Also characteristic – non-healing leg ulcers & recurrent bouts of abnormal chest pain
• 4 yr old black kid, long bones, enlarged spleen and liver, Lesion of skull Hair on end
• Homozygotes have sickle cell disease
♦ Occurs primarily in blacks
• Heterozygotes have sickle cell trait
♦ Relatively malaria resistant (balanced polymorphism)
• Becomes life-threatening when:
♦ 1) Damaged RBCs break down (hemolytic crisis)
♦ 2) The spleen enlarges & traps the RBCs (splenic sequestration crisis)
♦ 3) A certain type of infection causes the marrow to stop producing RBCs (aplastic crisis)
♦ **Repeated crises can cause damage to kidneys, lungs, bones, eyes, & CNS
• Blocked BVs & damaged organs can cause acute painful episodes (occur in almost all pts at some point)
♦ Episodes can last hours to days, affecting bones of the back, long bones, & the chest
• Complications – aplastic crisis due to B19 parvovirus infection, autosplenectomy, increase risk of encapsulated organism infection, Salmonella osteomyelitis, painful crisis (vaso occlusive) & splenic sequestration crisis
3) Thalassemias:
• Group of inherited disorders resulting from imbalance in production of 1 of 4 chains of aa/s making up hemoglobin
• Characterized by low levels of erthhyrocytes & abnormal hemoglobin
• Common in Mediterranean populations (ThalaSEAmia)
• Alpha Thalassemias:
♦ Due to gene deletion
♦ No compensatory increase of any other chain. Some forms result in hydrops fetalis and intrauterine fetal death
• Beta Thalassemias:
♦ Due to defect in mRNA processing
♦ Beta chain is underproduced
♦ In beta thalassemia major (homozygous), the beta chain is absent – results in severe anemia requiring blood transfusion. Cardiac failure is due to secondary hemochromatosis
♦ In both cases, fetal hemoglobin production is compensatorily increased but is inadequate
♦ HbS/beta thalassemia heterozygotes has mild to moderate disease
4) Hereditary Spherocytosis
Macrocytic anemia/Megaloblastic:
Any anemia in which average size of circulating RBCs is greater than normal
Frequently caused by deficiency of folic acid & Vit B12 (cyanocobalamin)
• These are associated w/ hypersegmented PMNs
• Unlike folate deficiency, Vitamin B12 is associated w/ neurologic problems
• Unlike folate deficiency, Vitamin B12 is associated w/ neurologic problems