Erythrocyte Disorders) Flashcards
In a CBC:
RBC measures
Hemoglobin measures
Hematocrit measures
MCV measures
MCHC measures
RBC = # of red blood cells
Hemoglobin = Amount of hemoglobin in blood (Red color, oxygen carrying)
Hematocrit = Percent of volume that RBCs take up in blood
MCV = Average volume (size) of red blood cells
–>Microcytic, normocytic, Macrocytic
MCHC = Concentration of hemoglobin in an average red blood cell
–> Hypochromic, Normochromic
Anemias are defined on the basis of….
Cell Size (MCV) and amount of Hgb (MCH)
If MCV is less than the lower limit of normal it is what type of anemia?
Normal Range?
Greater than the upper limit?
Microcytic Anemia
Normocytic Anemia
Macrocytic Anemia
If MCH is less than the lower limit of normal, it is what type of anemia?
If MCH is within the normal range?
Hypochromic Anemia
Normochromic Anemia
An means
Emia means
An = Without Emia = blood
This is defined as a reduction in HEMOGLOBIN concentration in circulating blood, resulting in tissue hypoxia due to lack of oxygen-carrying capacity of blood
Anemia
Symptoms of this illness include pale skin and mucous membranes, jaundice (if hemolytic), Tachycardia, Breathlessness, Dizziness, and Fatigue
Anemia
There are three ways to become anemic…
Lose Blood
Destroy Too Much Blood (hemolysis)
Make Too Little Blood
Hemolysis (anemia) can happen for 2 reasons
Extracorpuscular
Intracorpuscular
When the cause of anemia is losing blood, it is what type of anemia?
When the cause is destruction of too much blood, it is what type of anemia?
When the cause is making too little blood, it is what type of anemia?
Blood loss (hemorrhage)
Hemolytic
Bone marrow suppression/nutritional deficiencies
The etiology of blood loss anemia is traumatic, acute blood loss NOT > 20%
At first the hemoglobin level is normal. After 2-3 days, we see what (have ribosomal RNA, and no nucleus)?
Chronic Blood loss is different, and due to…
Reticulocytes
Iron Deficiency Anemia
Hemolytic anemia is due to decreased red cell lifespan. It can be chronic or acute.
This type is inherited and due to red cell defects
This type is aquired
Intracorpuscular
Extracorpuscular
In hemolytic anemia, increased bilirubin, increased LDH, and decreased haptoglobin are signs of….
Destruction
In hemolytic anemia, increased reticulocytes and nucleated red cells in blood are signs of….
Production (of red cells?)
This extracorpuscular cause of hemolytic anemia is due to physical trauma to red cells, schistocytes (fibrin strands that shred RBCs), and triangulocytes. It is important to find out why it is occurring
Microangiopathic Hemolytic Anemia
The causes of this illness include:
Artificial Heart Valves Malignancy Obstetric Complications Sepsis Trauma
Microangiopathic Hemolytic Anemia
This type of anemia is characterized by IgG, the spleen, and spherocytes
Warm Autoimmune Hemolytic Anemia (Warm AIHA)
This type of anemia is characterized by IgM, complement, intravascular hemolysis, and agglutination
Cold Autoimmune Hemolytic Anemia (Cold AIHA)
This is the most common form of AIHA
_____ antibodies bind to RBCs best at 37 degree body temperature (98.6F)
What occurs in the spleen?
Warm AIHA
IgG
Splenomegaly
In Warm AIHA, these RBCs are formed from nibbling by macrophages (Kupfer cells) causing loss of membrane, leading to a spherical shape
Spherocytes
This is the less common AIHA
_____ antibody binds to RBCs at 0-4 degrees celsius, in the ears, hands, and toes in cold weather
It causes extravascular hemolysis via membrane attack complexes in what organs? (2)
Cold AIHA
IgM
Spleen and Liver
In cold AIHA, this is binding of IgM that causes cross linking of red cells, and sludging of blood
What can it ultimately lead to?
Agglutination
Raynaud’s Phenomenon
This is a test for AIHAs, it can detect the antibodies on RBCs using blood samples
Direct Coombs Test/Direct Antiglobulin Test
A determination of warm AIHA is positive for what?
A determination of cold AIHA is positive for what?
IgG
Compliment
Warm AIHA can be secondary to 2 things
It can also be induced by:
Lymphoproliferative Disorder and Autoimmune Disease
Drugs
Cold AIHA can be secondary to 2 things
Infection and Lymphoproliferative Disorder
What is found in the blood film of warm AIHA
Cold AIHA?
Warm: Spherocytes
Cold: Agglutination
This is an intracorpuscular anemia characterized by QUALITATIVE defect in hemoglobin (aka hemoglobinopathy)
Sickle Cell Anemia
This intracorpuscular anemia is characterized by a single AA substitution in the beta chain of hemoglobin
It can be heterozygous or homozygous, which has worse prognosis?
It creates these cells which are fragile (burst easily), and they get stuck in vessels
Sickle Cell Anemia
Homozygous
Sickle Cells
In sickle cell anemia, what kind of mutation occurs in the Beta chain gene, leading to abnormal beta chains?
The cell will aggregate and polymerize upon deoxygenation. They get stuck in vessels and are fragile.
Point Mutation (valine substituted for glutamate)
Sickle Cell Anemia is more prominent in what ethnic group?
It’s severity is variable
Blacks
What 3 things does sickle cell disease cause?
Treatment includes preventing triggers, vaccinating, and blood transfusion
Chronic Hemolysis, vaso-occlusive disease, and increased infections
This intracorpuscular anemia is a hereditary QUANTITATIVE defect in Hb. Not enough alpha or beta chains can be made. It has variable disease severity
Thalassemia
What type of anemia is thalassemia?
Hypochromic, microcytic with increased RBC and target cells
This blood disease causes tons of spherocytes with a spectrin defect.
What cures it?
Hereditary Spherocytosis
Splenectomy
Hereditary Spherocytosis is autosomal ______
It causes a defect in the RBC membrane due to a mutation in ______, a membrane protein
Dominant
Spectrin
Hereditary Spherocytosis causes spheroidal erythrocytes called ______ that are more vulnerable to sequestration/destruction by the spleen
On smears, red cells lack normal central pallor
Also, splenomegaly (enlargement of spleen)
Spherocytes
40-50% of patients with hereditary spherocytosis experience _____
Gall stones (cholelithiasis)
Glucose-6-Phosphate Dehydrogenase Deficiency causes increased ______ which cause cell lysis
Related to exposure to what kind of drug?
G6PD is self limiting
Peroxides
Oxidative Drug
What cells develop in G6PD due to removal of Heinz bodies?
Bite Cells
In G6PD, some patients are asymptomatic
Other have _____________ hemolysis triggered by broad beans (favism-Africa), drugs (antibiotics, aspirin, infections)
It resolves spontaneously
Episodic hemolysis
Look at chart on the role of G6PD on slide 62 related to pentose phosphate pathway
!
G6PD deficient cells die in part due to reduced ______, oxidants attack hemoglobin bonds
This causes heme to break away from globin, globin denatures and sticks to the RBC membrane, forming ______
This organ bites out Heinz bodies, leading to bite cells?
GSH
Heinz Body
Spleen
Anemia associated with making too little blood has too few building blocks, like this type
Or it can be due to too few erythroblasts, like this type
Or there could be not enough room, like this type
Iron Deficiency Anemia
Aplastic Anemia
Myelophthlistic Anemia
The most important cause of iron deficiency anemia is
GI Bleeding
What category of anemia is iron deficiency anemia?
It’s a symptom, not a disease! Must find cause.
Microcytic, hypochromic anemia
This is a symptom of iron deficiency anemia, tongue inflammation/loss of papilla
Atrophic Glossitis
There are 3 causes of iron deficiency
Decreased iron intake (bad diet, bad absorption)
Increased iron loss (GI bleeding, menstrual cycle, hemorrhage)
Increased iron requirement (pregnancy)
Anemia caused by infections (osteomyelitis, endocarditis), inflammation (immune disorders like RA), and malignancy are anemias of chronic disease. Iron metabolism may be disturbed. It is usually mild anemia. What type of anemia is it?
Normochromic, normocytic
These are anemias of defective DNA synthesis, and has nuclear/cytoplasmic asynchrony
It is caused by a decrease in these molecules, associated with pernicious/folate anemia
Megaloblastic anemia
B12/Folate
What type of anemia is a megaloblastic anemia?
Macrocytic, hyperchromic
Vitamin B12 is needed to make..
DNA! (Megaloblastic anemias)
Anemias of Chronic Diseases are caused by,..
Iron metabolism is disturbed
What are the RBCs under the microscope?
Is anemia mild or severe?
Infections
Inflammation
Malignancy
Normochromic, normocytic
Mild
Megaloblastic anemia is initially caused by retarded _____ synthesis
Which leads to impaired ____ synthesis
Which leads to cells that look like what?
DNA
RNA
Big cells, with immature nucleus and mature cytoplasm
This can occur with megaloblastic anemia, and includes tongue swelling and loss of papilla (discussed earlier as well)
Atrophic Glossitis
This type of anemia is characterized by pancytopenia (deficiency of all three cellular components of the blood), empty marrow, and idiopathic etiology
Aplastic Anemia
There are 5 potential causes of aplastic anemia
Idiopathic Drugs Viruses Pregnancy Fanconi Anemia
This red blood cell disorders causes RBCs to be released from marrow in excess quantities. It has an unknown cause.
Polycythemia
Polycythemia is caused by hyperplasia of what?
Erythroid Precursors
In polycythemia, increased MCV/ viscosity leads to….
What disease develops?
Organ Congestion
Leukemia
This anemia is when there is not enough room
Myelophthisic Anemia
What is the cause of myelophtisic Anemia?
Associated with anemia and thrombocytopenia
Extensive inflitration of marrow by a tumor/lesion
metastatic breast, lung, or prostate cancer, and advanced TB
Right heart failure leads to what?
Congestion of peripheral tissues which leads to liver and tract congestion, as well as edema and ascites
Left heart failure leads to what?
Decreased cardiac output (leads to activity intolerance and signs of decreased tissue perfusion)
Pulmonary congestion
When left heart failure leads to pulmonary congestion, what occurs?
Impaired gas exchange and pulmonary edema (look at diagram with heart on it)
Cyanosis and pulmonary edema (dyspnea) are consequences of failure on which side of the heart?
Left
Hepatomegaly, jugular venous distention, splenomegaly, ascites, and peripheral edema are consequences of failure on which side of the heart?
Right
This is a major health problem affecting 25% of the population, it is asymptomatic until late. It contributes to coronary artery disease, stroke, cardiac hypertrophy, and heart failure
Hypertension
What is the cause/mechanism of hypertension?
Depends, but largely unknown (idiopathic)
What is the clinical measure of hypertension?
> 140/90
This is idiopathic hypertension, and comprises 95% of hypertension cases
Essential Hypertension
This hypertension comprises 5% of hypertension cases
Secondary Hypertension
This is the classification for BP > 180/120
Malignant Hypertension
This is hypertension that is urgent (180/110) or is an emergency (with end organ damage)
Hypertensive Crisis
What are the boundaries for classification of hypertension?
Normal
>120 and >80
Pre-hypertensive
120-139 or 80-89
Stage I
140-159 or 90-99
Stage II
greater than or equal to 160, or greater than or equal to 100
White essential hypertension is idiopathic, it may be related to:
Reduced ______ excretion
______ disease
______ factors
_____ factors
Sodium Excretion
Vascular Disease
Genetic Factors
Environmental Factors (Drug, EtOH)
Essential hypertension accelerates what condition?
It potentiates what 2 conditions?
Atherogenesis
Aortic Dissection and Stroke
Essential hypertension causes small blood vessels to narrow, especially in this organ
It hardens the arteries, leading to either:
Benign hypertension, called
Severe Hypertension, called
Kidneys
Hyaline Arteriosclerosis
Hyperplastic arteriosclerosis
This is defined as normal, clot free blood flow that is able to form a hemostatic plug if there is vascular injury
Hemostasis
This is the pathological counterpart of hemostasis, the formation of a blood clot within a vessel
Thrombosis
This is a solid mass of coagulated blood inside an uninjured vessel in the cardiovascular system (or after a relatively minor injury
It may be life saving or life threatening, clotting stops bleeding but can block a blood vesse
Thrombosis
This is an intravascular solid, liquid, or gaseous mass carried by the blood to a site distant from its point of origin
What do they mostly derive from?
Embolism
Thrombuses (this process is called thromboembolism)
Eventually, emboli lodge in vessels that are too small.
This type of embolism causes necrosis of downstream tissue (infarction)
This type of embolism causes hypoxia, hypotension, right sided heart failure
Systemic Embolization
Pulmonary Embolization
This is the term for venous emboli that eventuall block pulmonary arteries, leading to death.
Most are small and silent
Pulmonary Thromboembolism
Pulmonary thromboembolisms originate 95% of the time from?
Deep Vein Thrombosis (thrombi in deep leg)
This is an arterial emboli
80% arise from ____________ Thrombi
Final resting place depends upon their point of origin
75% or the time it ends up here
10% of the time it ends up here
Systemic Thromboembolism
Intracardiac Mural Thrombi
Lower extremities (75%)
CNS (10%)
When an infarct occurs in a myocardial location is called
Coagulative Necrosis
When an infarct occurs in a cerebral location it is called
Liquefactive Necrosis
When an infarct occurs in the pulmonary system, it is called this and associated with this disease
Caseous Necrosis
TB
When an infarct occurs in the bowels it is called
Liquefactive Necrosis
When an infarct occurs in the distal extremities, it is called
Gangrenous Necrosis
This is a retroviral disease of the lentivirus family and is characterized by a depletion of CD4+ T-lymphocytes and profound immunosuppression
AIDS
How many people are infected with AIDS in the US?
In Africa?
When were the peak number of deaths in
1 million
23 million
1995 (it’s been declining since)
Transmission of AIDS occurs via
What percent of it occurs in male-male sex?
Heterosexual contact?
IV Drug Use?
Blood Transfusion?
Parental Transmission to fetus/newborn?
Exchange of blood or bodily fluids
48%
34%
16%
1%
1%
AIDS transmission is extremely low risk for dentists when protective barriers are worn
Seroconversion from a needle stick/exposure of nonintact skin from an HIV patient occurs at what percent per exposure?
For a patient with hepatitis it is…
0.3%
6-30%
What is the structure of HIV?
RNA retrovirus
How many strands of RNA are in the AIDS virus?
What core does it have?
What type of membrane does it have, where is it derived from, and what does it have in its surface
2 single strands
Viral protein core (p24)
Phospholipid bilayer derived from the host cell membrane and studded with gp120 and gp41
HIV entry into host cells requires what molecule?
What envelope protein of the virus fuses with the CD4 cell membrane, binding the virion to the cell?
Which envelope protein inserts into the target membrane, fusing the virus with the cell?
The virus then enters what part of the host cell?
CD4
gp120
gp41
Cytoplasm
In the progression of HIV infection, during initial infection, the first cells infected are ____________
This results in major depletion of lymphocytes
Mucosal Lymphoid tissue CD4+ T cells
In the progression of HIV infections, during the acute phase (which is after initial infection), viral replication leads to _____ within days (about 3-6 weeks)
The host immune response is termed
Viremia
Acute HIV Syndrome
This occurs during the acute phase of HIV infection, and is nonspecific symptoms of any virus like fever, sore throat, occurring between weeks 3-17
So viral load is low at 12 weeks
Acute HIV Syndrome
During progression of HIV infection, during the chronic phase (after the acute phase), there is continued T cell depletion with new CD4 cells being made but unable to keep up with loss for several years
What occurs?
Asymptomatic or persistent lymphadenopathy
May have zoster or candida infection
During this phase of progression of an HIV infection, the CD4 count is less than 500 cells/ul, fever is present for one month, and there is weight loss/fatigue
Crisis Phase
During this phase of progression of HIV infection, the CD4 cell count is less than 200 cells/uL, leading to pneumonia/TB, opportunistic infections, malignancies, AIDS dementia
It occurs by how many years if left untreated?
AIDS
10 years (antiretrovirals have changed the course of the disease)
Regarding cells affected by HIV, these are the first immune cells effected
Its count eventually declines, and this ratio declines as well
CD4+ Inducer T cells
Helper/suppressor ratio (CD4/CD8 ratio)
These cells are affected by HIV becasue there is reduced response to specific antigens due to loss of stimulation from T-helper cells
B cells
These cells affected by HIV are mucosal and capture the virus, transporting it to regional lymph nodes.
Follicular ones in the germinal centers of lymph nodes are important ______ of HIV
Dendritic Cells
Reservoirs
These cells are affected in tissues by HIV, like CD4 T cells
Where specifically does this occur?
Why are they a good reservoir for HIV?
Monocytes/Macrophages
Brain and Lungs
They are resistant to the cytotoxic effects of HIV
(AIDS malignancies) This used to be the most common AIDS tumor, but has decreased due to antiretroviral treatment
What areas does it affect
What virus causes it?
Kaposi Sarcoma
Mouth, skin, lungs
Herpes virus HHV-8
This is the 2nd most common AIDS malignancy in patients
What virus plays a role?
Lymphoma of the _____ is considered an AIDS defining condition
Non-Hodgkin Lymphoma
EBV
Brain
AIDS defining cancers (Kaposi, Lymphoma) are on the decrease due to antiretrovirals
Non AIDS defining cancers are increasing
Liver Cancer, Hodgkins lymphoma, Anal Cancer
