Pathophysiology 1 Exam #2

Total blood volume in men

75.5 mL/kg

Total blood volume in women

66.5 mL/kg

Plasma makes up what percent of the blood volume?

~55-60%

Blood cells make up what percent of blood volume?

~40-45%

Plasma is composed of what?

92% water, 7% plasma proteins, and 1% hormones, vitamins, enzymes, lipids

True or False: Red blood cells have a nucleus

False, red blood cells lack a nucleus.

Blood is what % of body weight?

7-8%, around 5-6 Liters total

What is erythropoietin?

Hormone from kidney that stimulates erythrocyte production

Per 1 hemoglobin molecule, how many oxygen molecules can bind to it?

4 oxygen molecules

What do hemoglobin carry?

oxygen molecules in the blood

Where does the production of hemoglobin take place?

In immature RBCs

What is required for hemoglobin synthesis

Iron

What nutritional requirements are needed for normal RBC development?

Protein and Vitamins B12, Riboflavin, Folate, Niacin, B6, E, & C

RBC + Bone marrow precursors =

Erythron

A decrease in hemoglobin decreases what in kidneys?

Decreases the tissue oxygen tension in kidneys

What do RBCs need energy for?

To survive ~120 days and to operate membrane pumps for maintaining

• high intracellular potassium ion

• low intracellular sodium ion

• very low intracellular calcium ion

Where do RBCs get digested by macrophages?

In the spleen and liver

True or False: The 3% that is dissolved in plasma is measured as PO₂

True

True or False: Globin and iron portions are conserved and reused

True

What does the oxygen-hemoglobin dissociation curve describe?

The relationship between PO₂ (pressure) and SO₂ (saturation)

What process does RBC rely on to produce energy, due to no organelles?

Glycolysis

• produces 2 pyruvates and 2 ATP molecules

What three forms is CO₂ transported as?

• dissolved gas (5%)

• bicarbonate ion (75%)

• in association with hemoglobin forming carbaminohemoglobin (20%)

PaO₂ =

PO₂ in arterial blood = 80-100 mmHg

PvO₂ =

PO₂ in venous blood = 35-40 mmHg

True or False: Carbaminohemoglobin releases CO₂ in the lungs which we exhale out

True

Decreased oxygen reaching the tissues results in secretion of ____ and increase in the production of ___

erythropoietin (EPO); RBCs

What are the RBC disorders?

Anemia and Polycythemia

General Anemia Definition

Deficit of RBC

• Patient has tissue hypoxia due to low-oxygen-carrying capacity of blood

General Polycythemia Definition

Excess of RBC

• Patient has increased blood viscosity and volume due to the increase in RBC numbers

Relative anemia

• “dilutional anemia”

• normal total red cell mass with disturbances in regulation of plasma volume

• too much plasma = proportion of RBC to plasma is small

Relative anemia example

in pregnancy plasma volume increases ~40%

Absolute Anemia

• actual decrease in numbers of red cells

  • decreased production

  • increased destruction

General effects of anemia

• reduction in oxygen-carrying capacity

  • tissue hypoxia (low oxygen)

• compensatory mechanism to restore tissue oxygenation

  • increased heart rate

  • increased cardiac output

  • preferential increased flow to vital organs (limits blood flow to extremeties = paler skin)

  • increase in erythropoietin

Describe mild anemia

• usually no clinical symptoms

• elderly with cardiovascular, pulmonary disease may have symptoms

Describe mild to moderate anemia

• fatigue

• generalized weakness

• loss of stamina, followed w/ tachycardia and exertional dyspnea

Describe moderate to severe anemia

• decrease in blood pressure (orthostatic)

• intermittent claudication (muscle cramping)

• headache, lightheadedness, and faintness

• tinnitus (roaring in ears)

• tachypnea, dyspnea

• tachycardia

• vasoconstriction

• pallor

Aplastic anemia etiology and pathogenesis

• stem cell disorder characterized by reduction of hematopoietic tissue, fatty marrow replacement

• caused by toxic, radiant, or immunologic injury to the bone marrow stem cells

Aplastic anemia laboratory features

• pancytopenia (low RBC, WBC, and platelets)

  • low WBC important for prognosis: low leukocytes = susceptibility to infections

• diagnosed with bone marrow biopsy

Aplastic anemia clinical manifestation

• insidious onset of symptoms

• late symptoms

• thrombocytopenia (prone to bleeding)

• neutropenia (prone to infections)

• disease of the young

Aplastic anemia treatment and prognosis

• determine efficacy of bone marrow transplantation

• administer immunosuppressive therapy or stimulate hetopoiesis and bone marrow regeneration

• will be fatal unless bone marrow transplant successful

• bone marrow highly successful and curative for majority of untransfused patients, and 55% of patients with multiple transfusions

Anemia of chronic renal failure etiology and pathogenesis

• primarily from failure of the renal endocrine function, which causes impaired erythopoietin (EPO) production

• secondarily from failure of renal excretory function

  • leading to hemolysis, bone marrow cell depression and blood loss

Anemia of chronic renal failure laboratory features and clinical manifestations

• low RBC, hematocrit, hemoglobin count

• grossly deformed RBC

• general signs and symptoms of anemia usually manifest when hematocrit decreases <20%

Anemia of chronic renal failure treatment and prognosis

• dialysis

• administration of erythropoietin

  • EPO is only used until hemoglobn is 12 g/dL

• replacement of iron, folate, and B₁₂ due to dietary restrictions and anorexia

• 95% respond to erythropoietin therapy

Anemia in relation to vitamin B₁₂ or folate deficiency causes a disruption in what

DNA synthesis of blast cells produces megaloblasts (macrocytic)

Pernicious anemia is caused by lack of what which causes what

intrinsic factor which leads to vitamin B₁₂ deficiency

• problem is with B₁₂ absorption NOT deficiency

Anemia related to Vitamin B₁₂ or folate deficiency laboratory features

• low RBC, WBC, and platelet counts = megaloblastic dysplasia

• microcytic and hyper-segmented neutrophils

Clinical features of vitamin B₁₂ deficiency

• paranoia, dementia, cognitive dysfunction, delusions, hallucinations

• peripheral nerve degeneration and memory impairment

Clinical features of both B₁₂ and folate deficiency

• Edema in feet

• tachypnea

• weight loss

Vitamin B₁₂ or folate deficiency anemia treatment and prognosis

• administer B₁₂ and folate parenterally or orally

• majority respond well to treatment

• reversibility of the neurologic damage is low though

Most common cause of anemia

Iron deficiency anemia

Iron deficiency anemia cause

unavailability of iron for hemoglobin synthesis

Iron deficiency anemia laboratory features

• smaller and paler RBC

• low red cell indices

• decreased serum ferritin

Iron deficiency anemia treatment and prognosis

• oral administration of ferrous sulfate

• treat underlying cause

• prognosis is very good usually

possible causes of iron deficiency anemia

• increased requirement for iron (ex. pregnancy)

• excessive iron loss (ex. hemorrhage)

• diminished absorption

• low iron intake

• renal failure

• hemodialysis

• GI bleed

• menorrhagia

True or False: Thalassemia has increased RBC destruction referred to as hemolysis

True

Thalassemia etiology and pathogenesis

• associated with mutant genes that suppress rate of globin chain synthesis

• classified by the polypeptide chain(s) with deficient synthesis

  • a-thalassemia or b-thalassemia

  • most clinically severe form: thalassemia major (homozygous)

Sickle cell anemia etiology and pathogenesis

• genetically determined defect of hemoglobin synthesis resulting in hemoglobin instability and insolubility

• in Hemoglobin S, a single amino acid substitution causes the structural abnormality

• sickled cells cause vascular occlusion

  • cant carry enough O²

  • sickled shape RBC stacks on each other = blockage

For hemolytic newborns, what is clinically relevant?

Rh incompatibility

• fetal RBCs cross placenta and stimulate production of maternal antibodies against antigen on fetal RBC - not from mother

• maternal antibodies cross into fetal circulation causing destruction of fetal cells in subsequent pregnancies

Hemolytic disease of the newborn treatment and prognosis

• standard dose of anti-Rh immune globulin (RhoGAM) is given to mother before or after delivery

• severe cases in utero blood transfusion and early delivery

• prognosis: death, possible retardation, or barely perceptible hemolytic process

antibody-mediated drug reactions cause

exposure to a drug causes destruction and lysis of sensitized person’s own RBCs

antibody-mediated drug reactions treatment and prognosis

• recognition and discontinuation of responsible drug

• steroid therapy i cases of severe hemolysis

acute blood loss treatment and prognosis

• blood volume replacement therapy with crystalloids, colloids, and fresh whole blood

• prognosis is excellent with treatment unless blood loss is severe

Polycythemia definition

excess RBC results in increased blood viscosity, leading to clinical symptoms such as hypertension

Polycythemia Vera

neoplastic transformation of bone marrow stem cells

• “true polycythemia”

• absolute increase in RBC mass, leukocytosis, thrombocytosis - increased uric acid because of excess proliferation, oxygen saturation is normal

Secondary Polycythemia

caused by chronic hypoxemia with resultant increase in erythropoietin production

• increased RBC production without increase in WBCs or platelets

Relative Polycythemia

caused by dehydration with spurious increase in RBC production

• elevated hematocrit, hemoglobin, and RBC count

• two groups: disturbed fluid balance and stress polycythemia

What defines heart failure?

Inability of heart to maintain sufficient cardiac output to meet metabolic demands of tissues and organs

Heart failure (HF) is a potential consequence of

Most cardiac disorders

True or False: Mortality for HF is high, 50% of patients die within 5 years of diagnosis

True

Most common cause of HF?

• myocardial ischemia (CHD) followed by

• hypertension

• dilated cardiomyopathy

What does HF result from?

Impaired ability of myocardial fibers to contract, relax, or both

Symptoms of fluid overload sometimes are described as

congestive heart failure in HF patients

When it comes to Systolic Dysfunction with low ejection fraction, what is reduced contractility evidenced by?

low ejection fraction (EF) and reduced muscular contraction during ventricular systole

What is a common etiology of Systolic Dysfunction with low ejection fraction?

Myocardial infarction

What are less common causes of Systolic Dysfunction with low ejection fraction?

heart defects, valve disorders, respiratory diseases, anemia

Diastolic Dysfunction with preserved Ejection Fraction is a disorder of

Myocardial relaxation

• Left ventricle is excessively noncompliant and does not fill effectively

What is the hallmark of diastolic dysfunction with preserved ejection fraction?

Patients exhibits low cardiac output, congestion, and edema formation with normal ejection fraction

What is increased preload defined as?

A compensatory mechanism that enhances the ability of the myocardium to contract more forcefully.

Current management of HF directed toward reducing the harmful consequences of these compensatory responses:

• increased heart rate and contractility (though SNS activation)

• increased preload

• myocardial hypertrophy

HF impacts afterload on which ventricle?

the left ventricle - it increases

Clinical presentation depends on which ventricle (left or right or both)

is failing to pump blood adequately

Forward effects of HF

inadequate ability to push the blood forward by the pumping ventricle (cardiac output)

Backwards effects of HF

Congestion of blood behind the pumping ventricle

Left-sided HF causes what type of edema?

pulmonary edema

Right-sided HF causes what type of edema?

systemic edema

Biventricular HF causes what type of edema?

pulmonary and systemic edema

Left HF is most often associated with

Left ventricular infarction

Right HF is associated with

Right ventricular infarction

True or False: Biventricular heart failure is most often the result of primary left ventricular failure that has progressed to right sided heart HF

True

Describe biventricular HF

• cardiac output is reduced

• pulmonary congestion (due to LHF)

• systemic venous congestion (due to RHF)

True or False: Beta blockers inhibit SNS effects

True

What are dysrhythmias significant for?

• For indicating an underlying pathophysiologic disorder

• For impairing normal cardiac output

What are factors that cause dysrhythmia?

Hypoxia, electrolyte imbalance, trauma, inflammation, and drugs

What are dysrhythmias?

Also called arrhythmias, abnormality of the cardiac rhythm of impulse generation or conduction

Three major types of dysrhythmias

• abnormal rates of sinus rhythm

• electrical impulse generation from abnormal sites (ectopic)

• disturbances in conduction pathways

Describe normal sinus rhythm

• Starts in the SA node and follows the normal pathway

• P wave precedes every QRS complex

• PR, QRS, QT intervals are of normal duration

Impulse from the SA node goes through the atria, AV node, His/Purkinje system, and ventricular myocardium depolarizes or repolarizes?

Depolarizes

Electrical depolarization of the heart leads to

atrial and then ventricular muscle contraction

Tachycardia

Fast heart rate

Bradycardia

Slow heart rate