1
Q
Identify the WHO definition of health
A
State of complete physical, mental and social well-being and not merely the absence of disease or infirmity
2
Q
Definition of Pathophysiology
A
The study of the abnormalities in physiologic functioning of living beings
3
Q
Process of clinical reasoning
A
Steps in the thought process to get to your diagnosis
- *Take a good history
- *Develop DD list using +/- patient presentation
- *Order diagnostics based on DD
- *Prioritize the order of the differentials Possible vs Probable
4
Q
Process of Differential Diagnosis
A
- Most likely - prevalence demographics, risk factors, signs and symptoms
- Life-threatening - can’t miss it
- High prevalence - most common diagnosis
5
Q
Etiology
A
WHAT CAUSED THE DISEASE
- Idiopathic (unknown) Iatrogenic (treatment cause)
- Risk factor (presence increased the likelihood of the disease)
6
Q
Pathogenesis
A
Development or evolution of the disease from initial stimulus to full-blown disease and finish. Initial factors alter normal physiologic fx and lead to the development of clinical manifestations that are observed in a particular disorder/disease
7
Q
Clinical course of a disease
A
- Exacerbation - a sudden increase in severity of existing disease
- Remission - decrease in s/s (could be cure)
- Convalescence - stage of recovery after a disease, injury, or surgery
- Sequela - complications resulting from illness (flu recovered but dev pneumonia)
8
Q
Stages of disease
A
- Latent period - the time between exposure of pathogen and 1st s/s (asymptomatic)
- Prodromal period - 1st s/s occur indicating disease
- Acute phase -disease at full intensity; usually short-lived
- Exacerbation- sudden increase in severity
- Remission - decrease in severity, signs/symptoms
- Convalescence - stage of recovery after a disease, injury, or surgical procedure (rehab after stroke)
- Sequela - subsequent pathologic condition resulting from illness (pneumonia after flu)
9
Q
Differentiate between primary, secondary, tertiary prevention
A
- Primary - (P) Preventing disease: Seasonal flu shot, vaccinations, clean H2O, seatbelts, condoms, safe sex
- Secondary (S) Screening, early detection: screening mammogram, blood tests, screening colonoscopy, year physicals
- Tertiary (T) Medical Treatment (disease is there): medications, rehab, surgery, supportive care
10
Q
Function of Organelles and its components
A
Control center containing all genetic information. Nucleus, Endoplasmic Reticulum, Golgi complex, Mitochondria, Lysosomes
11
Q
Nucleus
A
- Performs work maintaining the cell’s life
- Largest organelle
- Contains DNA and RNA synthesized in the nucleus
12
Q
Endoplasmic Reticulum/Golgi Complex
A
Synthesize enzymes/proteins and packages them
13
Q
Lysosomes
A
Digests material - Phagocytosis
14
Q
Mitochondria
A
Converts energy for cellular reactions ATP production
15
Q
Anaerobic vs. Aerobic metabolism in ATP production
A
Anaerobic no oxygen needed (not as efficient in ATP production) vs aerobic needs oxygen (more efficient)
16
Q
Differentiate between diffusion, osmosis, passive/active transport
A
- Diffusion - movement of solutes from higher to lower concentration
- Osmosis - movement of solvent across cellular membrane from low to high solute area
- Passive transport is diffusion and facilitated diffusion and moves fluid from higher concentration to lower concentration without ATP Active transport is movement from lower to higher solute concentration area it involves a carrier molecule (ATP- energy)
17
Q
Describe active transport in relation to Na/K pump
A
Energy is required to move sodium out of the cell where the concentrations are high and move potassium into the cell where concentrations are high
18
Q
Differentiate between function of DNA vs RNA
A
- DNA replicates and stores genetic information. It is a blueprint for all genetic information in an organism.
- RNA converts the genetic information stored within the DNA to a format used to build proteins and then moves it to the ribosomal protein factories
19
Q
Identify the four types of cellular tissue
A
- Epithelial
- Connective
- Muscle
- Neural
20
Q
Epithelial Tissue
A
Lines outside and interior areas of the body. Squamous, cuboidal, and columnar cell shapes. Holds together cushions organs
21
Q
Connective Tissue
A
Large extracellular and fibroblast cells. Collagen, elastic, and reticular types Holds organs together, cushions organs
22
Q
Muscle
A
- Cannot replicate
- Made of contractile fibers consisting of actin and myosin - Myocytes Smooth, cardiac, or skeletal
23
Q
Neural Tissue
A
Cannot replicate
- Neurons - conduct impulses
- Neurons cell body, axon, dendrites
- Neuroglial cells - supporting role
- Astrocytes - BBB
- Oligodendrocytes - myelin in CNS
- Schwann cells - myelin in PNS
- Microglia - phagocytic cells
- Ependymal - produce CSF
24
Q
Proliferation
A
The process by which cells divide and reproduce. The rate is determining factor. If the rate is abnormal develop neoplasms.
25
Differentiation
Process by which cells become specialized by:
## Footnote
* Type
* Function
* Structure
* Life cycle
Everything comes from stem cells
26
Adaptation
Cells attempt to prevent their own death from environmental changes through adaption. Modify size, numbers, and types in an attempt to maintain homeostasis. Adaption ceases once stimuli is remove. Atrophy - shrinks uses less resources Hypertrophy - enlarges Hyperplasia - increase # of cells (epithelial) - menses Metaplasia - adult cells are replaced by less mature cells. Cells still look alike. Initiated by chronic irritation and inflammation. Esophagus cells r/t GERD Dysplasia - mutation into cells of different size, shape, and appearance. Premalignant cell, next stage Ca. Can still be reversed
27
Describe the process of cellular injury and cellular death
Cellular injury is reversible up to a point. Cell death occurs by apoptosis or necrosis. Hypoxia is the most common cause of cellular injury. Apoptosis is programmed cell death at a certain point of development and there is no inflammatory response Necrosis - cell rupture, spilling of contents cause inflammation. Liquefaction (brain) cauceous (lung, TB), fat (pancreas), and coagulative (heart)
28
Explain the process of free radical damage and the role of antioxidants
Free radicals are unstable atom unipolar molecules in the body. The most concerning are those derived from oxygen and therefore called ROS. Free radicals attach to molecules and then make them unstable. Antioxidants are marketed as preventing and/or fighting disease and aging. Antioxidants travel through the blood vessels to reach damaged cells and supply the free radical with an electron to repair the free radical without damage to itself.
29
Differentiate between benign and malignant neoplasms
Neoplasm is cellular growth no longer responding to normal regulator processes (an error in the division of cells) Benign neoplasms are similar to normal cells faster growth than normal, localized, do not cause systemic effects. Malignant neoplasms are undifferentiated (nonspecific cell type), nonfunctioning cells that reproduce rapidly. Differ from normal cells in size, shape, and number. Invade nearby tissue and metastasize to distant tissue. Cause systemic effects. Genetic, epigenetic, and microenvironments factors. Epithelial - carcinoma Connective - sarcoma hematopoietic - leukemia Bone, liver, and lung most common areas of metastasizes
30
Identify common tumor cell markers
* Alfa fetoprotein - liver, ovarian, testicular germ cell ca
* CA 15-3 - breast, lung, ovarian, prostate
* Carcinoembryonic antigen - bladder, breast, cervical, kidney, liver, lung, lymphoma, melanoma, ovarian, pancreatic, stomach, thyroid
31
Autosomal Dominant Disorder
Single gene mutation Passed from affected parent to offspring - REGARDLESS OF SEX
Ex. Marfan's Syndrome - tall, thin, long arms, Aortic & Mitral valve murmurs, aorta abnormalities
32
Autosomal Recessive Disorder
Single gene mutation Passes from an affected parent - REGARDLESS OF SEX Both parents have to be carriers can skip generations before active disease occurs
Ex. Cystic Fibrosis
33
Sex-Linked Disorders Recessive or Dominant
Mostly X-linked Very little genetic material on Y chromosome. More males affected with more severe presentation
Ex. Hemophilia
34
Polyploidy
More than the normal 23 pairs in a cell
35
Aneuploidy
Abnormal separation during cell division - too many or too few chromosomes
36
Trisomy 21 Autosomal Aneuploidy
A spontaneous chromosomal mutation resulting in three copies of chromosome 21 Hypotonia Distinctive facial features Congenital heart defects Simian crease
37
Turner's Syndrome
Females - deletion of X chromosome Short lymphedema of hands and feet Broad chest wide nipples Low-set ears
38
Klinefelter's Syndrome
One or more extra X chromosomes and at least one Y (XXY) MALES
* Small penis. prostate gland, and testes
* Sparse facial and body hair
* Long legs short obese trunk
39
Identify the components of the immune system
Antigen-Antibody Autoantibody
Primary Lymphoid Organs
Secondary Lymphoid Organs
40
Antigen
Foreign agents that trigger the body to produce antibodies
41
Antibody
Proteins in the body that IDs and neutralizes foreign agents (virus/bacteria)
42
Autoantibody
An antibody that attacks itself
43
Primary Lymphoid organs
* Bone marrow - red marrow
* Thymus gland
* Lymphoid system Lymphocytes (T cells, B cells, Natural Killer cells)
44
Secondary Lymphoid organs
* Spleen
* Lymph nodes
* Tonsils
* Peyer patches
45
Describe the process of innate immunity
What we are born with. Interferons are released from cells that have an infected virus they put out this interferon to protect other cells from the virus. Bind to the plasma membrane to keep the virus from reproducing. Physical and chemical barriers found in the body Skin and mucous membranes (acidic skin and cilia) Natural Killer cells - react immediately Inflammatory response
46
Explain NK cells
Natural killer cells are not dependant on the thymus for development. Part of innate immunity will kill tumor and viral infected cells WITHOUT previous exposure. Do not need previous exposure to antigen. Will not affect cells with MCH1 protein to protect from autoimmunity
47
What role does the Thymus play in immunity?
Found in the mediastinum. Mature T lymphocytes that formed in the bone marrow.
48
Explain the sequence of the inflammatory response and the role of mast cells and mast cell mediators
Inital response is vasospasm to stop bleeding, clot, then vasodilates to get cells to help repair
49
Describe the complement system and the membrane attack complex
Plasma proteins to enhance and cause inflammation, gives chemotaxis (attracts neutrophils), lysis, and optimization (immediately flags cells for destruction shorter and faster than MAC) MAC creates a hole in a a bacterial cell membrane (mainly gram- bacteria)
50
Describe Adaptive Immunity and the difference between cellular immunity and humoral immunity
Recognized and destroy foreighn invaders and maintains a memory of it.
Cellular immunity (cell surfaces) T cells (CD4 and CD8) Humoral immunity (body fluids) B cells (memory or plasma cells) - mature in bone marrow and is aquired immunity. Floating around in the body looking for foreign invaders it remembers. Starts allergic rx's, prevents viral infections, eliminates bacteria and toxins. ABLE TO RESPOND RAPIDLY found mainly in peripheral tissue. Thousands produced die rapidly. Requires activation from T Helper cells (CD4) No thymus prevents this step
51
CRP and Sed Rate
Labs to show inflammation in the body
52
Compliment cascade Classical Pathway
Triggered by the antibody-antigen complexes (IgG, IgM) starts at C1 ends with MAC but takes longer than the alternative pathway
53
Compliment cascade Alternative Pathway
Triggered by bacterial endotoxin. Skips classical pathway goes to C3 and involves opsonization (immediate flag for phagocytosis) its a shortcut
54
CD4 cells
Type of T cell, Regulator (helper) cell involved in Adaptive Immunity
55
CD8 cells
Type of T cell, Effector (cytotoxic) cell involved in Adaptive immunity
56
Major Histocompatibility Complex
Part of adaptive immunity that is Human Leukocyte Antigen (HLA) in humans Marks the body cells as "safe" No one person has the same MHC except identical twins MHC1 is on every cell expect RBC's
57
IgM
Produced first! Lasts around 10 days M for immediate Active infection Activates complement system
58
IgG
Prior exposure to vaccine or virus. Can cross the placenta to provide immunity to the fetus (passive immunity)
59
IgA
* Skin
* MM
* Saliva
* Tears
* Colostrum
* Breast Milk
* Acts locally
60
IgD
On B cells works with IgM
61
IgE
Triggers histamine and cell mediators Allergic reaction or parasitic infection
62
Passive Immunity
Immediate protection can be temporary Immunoglobulins (serotherapy) - Rabies, Hep A&B - gives immediate immunity Mother to the fetus (IgG, IgA)
63
Active Immunity
Has had infection or immunization
64
Explain the different types of vaccines
Live - identical immune response as infection - no for immunocompromised
Inactivated Vaccine - Whole/fraction of virus/bacteria/toxin, humoral immune response (Polio, HepA)
Fractional Vaccine - Modified toxins (Tetanus, Ptosis, Pneumonia)
Recombinant Vaccine - Genetically engineered (HPV)
65
Type I Hypersensitivity Reaction
Immediate response - Histamine, Leukotrienes, Prostaglandins Histamine (mild hives, eczema seasonal allergies to wheezing, tachycardia to anaphylaxis) IgE, Allergy response, Asthma, Anaphylaxis T Cells bind to mast cells, stimulate B cells
66
Type II Hypersensitivity Reaction
Transfusion reactions and newborn hemolytic reactions Destruction of antigens on target cells or tissues resulting in lysis B cells, RBCs, WBCs IgM and IgG are principal antibodies
67
Type III Hypersensitivity Reaction
Autoimmune disorders - accumulation of circulating antigen-antibody complexes - B cells Targets tissues, joints, skin, kidneys, blood vessels causing glomuleronephritis 10-12 days after infection and triggers complement system
68
Type IV Hypersensitivity Reaction
PPD reaction, Dermatitis
Delayed processing of the antigen by macrophages. Antigen presented to T cells after processing Can take 24-72 hours to develop
NOT ANTIBODY-MEDIATED
ex. Contact dermatitis, TB, poison oak
69
Immunodeficiency
Increases susceptibility to infections, crucial to prevent infections
* Primary - congenital deficiency, defective CD4s, deficient complement system, deficient and defective adaptive system (sick more than you should be)
* Secondary - loss of spleen, medications
70
Autoimmunity
Failure to identify self-antigens from foreign antigens Genetic component, exacerbation and remission, previous Epstein Barr infection. Two methods of attack: Autoantibody, T cell mechanism triggered by viral/bacterial infections, environ/occ stress
71
Opsonization
A pathogen is marked for ingestion and eliminated by a phagocyte, C3b and antibodies are responsible for opsonization
72
B Cell Disorders
B - Bone Marrow Attack invaders on the outside of the cell and antibody secretion Deficiency in humoral or antibody-mediated immune responses B cells recognize surface antigens of viruses and bacteria and produce and secrete antibodies, activating the immune system to destroy the pathogens. They defend against viruses and bacteria that enter the blood and lymph. IgA deficiency, hyper-IgM syndrome
73
T Cell Disorders
Deficiency in Cell-Mediated immune responses. Can only recognize viral antigens outside the infected cells T cells defend against pathogens including protists and fungi that enter the cells. DiGeorge Syndrome, Wiskott-Aldrich syndrome
74
Difference between CD4 and CD8 cells
CD8 (cytotoxic cells) can kill cancer cells recognizes antigens, destroys viral cells, mutant cells CD4 (T-helper cells) leads the fight against infection, , activates macrophages, interacts with antigens; stimulates B Cell proliferation and antibody production.
75
3 types of HOST / MICROBE RELATIONSHIP
* Transient - food/water pass through without staying
* Commensal - normal flora
* Pathogen - cause disease
76
Physical barriers to pathogens
Epithelial cells (must be intact)
Sloughing of the skin
High-fat content of skin inhibits growth of bacteria & fungi
Mucous membranes trap
Cilia transport system in lungs sweep out
Frequent urine passes out bacteria
77
Biochemical barriers to pathogens
* Acidic environment of the skin, urine, vagina inhibits bacterial growth
* HCI in stomach kills organisms
* Saliva, mucous, tears, sweat have enzymes that are antibacterial
* Sebaceous gland secretions are antifungal
78
Risk factors that promote pathogen proliferation
Nutritional status, Age, Chronic Illness, Immunosuppression, Stress (cortisol)
79
Differentiate between high and low pathogen virulence
* High virulence can cause disease in a healthy
* individual Low virulence can cause disease in an immunocompromised individual
80
Routes of transmissions in pathogens
* Direct
* Indirect
81
Direct transmission (3) routes
1. Body fluids: droplet
2. Animal bites/soil
3. Placenta transfer - vertical transmission
82
Indirect transmission (3) routes
1. Vehicle borne - water, food, clothing, tissue
2. Vector-borne - insect carries
3. Airborne - droplets, measles, legionnaires (cooling towers)
83
Four types of pathogenic microorganisms
1. Bacteria
2. Viruses
3. Fungi
4. Parasites
84
Bacteria Characteristics
Various shapes Cocci (spherical) enterococcus
Bacilli (rod-shaped)
Vibrio (comma-shaped rods)
Pseudomonas Spirilla (twisted , spiral rod-shaped
Anaerobic - spirochetes
85
Viruses
Smallest known infective agents Composed of protein shell; capsid with core of DNA or RNA Some have protective envelope around the capsid Viruses have organelles bacteria don't which means they can mutate into different strains
86
DNA Viruses
DNA - Produce messenger RNA in host cell nucleus Viral proteins formed from mRNA Virus DNA replicted by host polymerases Ex. HSV
87
RNA Viruses Retrovirus
Retrovirus: contains enzyme reverse transcriptase; convert their RNA into DNA; incorporated into the host's DNA Ex HIV
88
RNA Viruses Replicating Virus
RNA viruses replicate within the cytoplasm and most produce mRNA which is then translated into proteins and genomic RNA, from which new viruses are created
89
Fungi
Have organelles Eukaryotic microorganisms with thick rigid cell walls Mycotic Infections caused by yeast Neutrophils, monocytes and eosinophils can destroy fungi Fungi thrive on glucose
90
Superficial (Fungi)
Superficial, dead, keratinized tissue, cause inflammation DO NOT INVADE TISSUE Ex. Tinea Pedis
91
Subcutaneous (Fungi)
Introduced during trauma Leads to ulcers and abscesses
92
Systemic (Fungi)
Inhalation of dust (from soil) More serious Affects immunocompromised hosts
93
Parasites
Establish themselves with another organism; benefit from the other organism Rarely transmitted by human contact Usually transmitted by a vector (malaria) Protozoal infections trans by food/water (Giardia) Commonly affect skin and GI tract
94
Protozoa
Single-celled parasite
95
Nemathelminthes
Roundworm parasite
96
Platyhelminths
Flatworm parasite
97
Five types of WBCs (Leukocytes)
_N_ever_L_et_M_onkeys_E_at_B_ananas
## Footnote
1. Neutrophils
2. Lymphocytes
3. Monocytes
4. Eosinophils
5. Basophils
98
Neutrophils
First responders to infection or inflammation Count 2,500 - 7,500 Half-life 6-8 hours Bacterial Release toxins can damage normal tissues
99
Lymphocytes
Immunity (B,T,NK cells)
Viral infections
Derived from Lymphoid stem cells Key cell involved in immune response
100
Monocytes / Macrophages
Macrophages - Infection _NON-GRANULOCYTES_ _Monocytes are immature macrophages_ that circulate in the bloodstream and become macrophages in the tissue. Macrophages can ingest more than neutrophils and live from month to years. Capable of cell division
101
Eosinophils
_Allergic or Parasitic Infections_ 1/2 life 12 days Major fx is to kill intestinal worms (helminths) can't be phagocytosed Release inflammatory enzymes and proteins
Half-life 12 days
102
Basophils and Mast Cells
_IgE Allergy In the bloodstream_ - _Granulocytes_ (0-2% of WBCs) _Basophil in connective tissue becomes MAST cell_ and can live months
BOTH cells contain histamine for allergic reactions have IgE receptors _ASTHMA, ANAPHYLACTIC RX)_
103
Neutrophilia
High neutrophil count stored in bone marrow - infection - usually bacterial
104
Bands or Granulocytes
Immature neutrophils that are in the bone marrow. They progress through the progranulocyte stage through myelocyte, metamyelocyte, band and mature neutrophil, each stage resulting in less RNA
105
Neutropenia
Low neutrophil count often from chemo or radiation Iatrogenic neutropenia - caused by us (chemo/radiation)
106
Macrophages
Mature monocytes Release cytokines to identify cells that dont belong (opsonization) Important in wound healing Important in antigen presentation Have C3b receptors to identify cells that have been opsonized
107
Leukemia
Circulating tumors that involve the blood and bone marrow
108
Lymphoma
Localized in the lymph tissue and disseminated to the other sites
109
Plasma Cell Myeloma
Malignant transformation of B cell plasma cells; also forms localized tumors in the bony structures
110
Left Shift of WBC
Immature bands are increased during infection. A left shift signals a big infection for days
111
Neutrophil Storage Pool
Neutrophils are in bone marrow & circulating blood 10 days for neutrophils to mature Majority of neutrophils are in marrow Mature cells are sent out first
112
Lymphoma
Localized in the lymph system and taken to other sites. Most common blood cancer
113
Leukemia
Circulating tumors that involve the blood and bone marrow. Cancer of the leukocytes. Cells do not die as they should and create overcrowding for the healthy cells
114
Plasma cell myeloma
Malignant transformation of B cell plasma cells; also forms bony tumors
115
Plasma cell myeloma
Malignant transformation of B cell plasma cells; also forms localized tumors in the bony structures
116
Hematologic Neoplasms
Based on cell type of the neoplasm instead of location. Used by WHO to classify Myeloid and Lymphoid Neoplasms
117
Myeloid lineage neoplasm
RBC's, platelets, monocytes, and granulocytes
118
Lymphoid lineage neoplasm
1. B cells
2. T cells
3. NK cells
119
Pathogenesis of Hodgkin's lymphoma
Typically starts in the lymph nodes of the upper body then spreads to other lymph nodes through lymphatic vessels. Node enlarges and compress surrounding tissue PAINLESS enlarged lymph node in neck and/or supraclavicular area; axilla, groin. Mediastinal mass/nodes on x-ray HAVE Reed-Sternberg Cells
120
Pathogenesis of B/T cell lymphoma
90% of all lymphomas and 5% of childhood cancers DO NOT HAVE Reed-Sternberg Cells
121
Hodgkin's Lymphoma vs. B/T Cell and NK-Cell Lymphoma
90% of all lymphomas Older adults DO NOT HAVE REED-STERNBERG CELLS NH Lymphoma - painless enlarged lymph nodes in the neck or supraclavicular area; axilla, groin. Mediastinal mass/nodes on chest X-ray. Fever, night sweats, weight loss, splenomegaly
122
Pathogenesis of Multiple Myeloma
Cancer of the plasma cells. Abnormal cancer cells migrate back to bone marrow increasing osteoclast (bone thinning) and abnormal "M protein" immunoglobulin. Bone pain is often in pelvis and pt has increased infections. Bone x-ray with show LYTIC lesions and they will have Bence Jones proteinuria
123
Pathogenesis of MGUS (Monoclonal Gammopathy of undetermined significance)
Prior to Multiple Myeloma When normal plasma cells begin to respond abnormally to antigens. The abnormal plasma cells make monoclonal antibodies. Predisposes patients to develop MM
124
Presentations of Acute Leukemia
Result of cytopenias (fatigue, SOB, bruising, bleeding, infections. Bone and joint pain Severe bone pain in children Lymphadenopathy, hepatosplenomegaly
125
Presentations of Chronic Leukemia
Generally ASYMPTOMATIC presentation PAINLESS local or general lymphadenopathy Three phases for CML - Chronic, Accelerated, Blast Phase
126
Identify the function and clinical process of Erythropoietin (EPO)
Regulator of red blood cell production. Produced in the bone marrow In response to hypoxemia and blood loss, supply the kidneys (liver in fetus) to produce EPO EPO is in the kidneys sends messages to the bone marrow
127
Function of B12 & Folate
Necessary in the development of RBCs for cellular DNA synthesis. Deficiencies can lead to the inability of the cell to undergo nuclear division, premature apoptosis, and phagocytosis of precursor cells. Both from dietary sources.
128
Explain RBC production
Produced in the bone marrow in response to erythropoietin Erythroblast (large nucleated cell) in marrow changes to reticulocyte in plasma with no nucleus (1% of RBCs) Reticulocyte matures in the bloodstream in 24-48 hours to become a mature erythrocyte RBC life span 80-120 days in plasma Biconcave disc shape with reverse deformability
129
Discuss iron transformation process and the end role of ferritin
Dietary source absorbed in the duodenum and proximal jejunum. After absorption iron is bound, used, transported or stored. Transferrin binds and transports iron in the plasma and into the cell then Ferritin binds with Transferrin as stored iron in the liver as ferritin
130
Transferrin
Transferrin is a protein that transports iron in the plasma. Transferrin iron receptor on the RBC cell membrane to pass iron into the cell.
131
Hepcidin
Hepcidin controls how much iron is bound transported into the cells. Protein found in the liver. Regulated dietary iron uptake from GI. Allow or inhibits iron transport across cell membrane by binding to the transport. Low iron = less Hepcidin production. High iron = more Hepcidin production
132
What is needed for DNA synthesis in the cells?
B12 and Folate
133
What nutritional requirements are needed for erythropoiesis
B12, Folate, B6, Riboflavin, niacin, ascorbic acid, Vit E
134
What is needed for B12 absorption?
Intrinsic factor secretion from parietal cells in the stomach
135
Explain the role of reticulocytes
Reticulocytes are immature RBCs. Their number in circulation is an indicator of bone marrow response to anemia.
136
What does a low reticulocyte count tell you?
May occur when the bone marrow is able to produce but cannot make RBCs such as iron, folic acid, vitamin B12, or erythropoietin. Reticulocyte count is an indicator of the status of RBC production
137
What is Macrocytic RBCs
Larger than normal RBC. Macrocytosis is caused by nutritional deficiency, specifically of folate or vitamin B12. This can arise from a hereditary condition called pernicious anemia, in which a protein called intrinsic factor is lacking in your gut.
138
What is Microcytic RBCs
Smaller than usual RBC. Causes of microcytosis are iron deficiency anemia and thalassemia
139
What is hypochromic RBCs
Hypochromia means that the red blood cells have less color than normal. This usually occurs when there is not enough of the pigment that carries oxygen (hemoglobin) in the red blood cells. Can be caused by a lack of iron and B6 deficiency
140
What is normocytic RBCs
Normal shape and size of RBCs but not adequate #s of circulating RBCs to carry O2 to organs. Usually the result of a chronic condition
141
Define Anemia
Lack of RBCs. Impairs oxygen-carrying capacity of the blood, decreased RBC [production or increased RBC loss.
142
Iron Lab Values
Normal 70-175 (m) 50-150 (f)
143
TIBC Lab Values
Normal 250-450 mcg/dl If Fe is low TIBC is high If Fe is high TIBC is low
144
Ferritin Lab Values
Normal 18-270 (m) 18-160 (f) Stores of iron - tells us how long the anemia has been going on. Chronic inf. conditions (autoimmune) Inflammation can raise ferritin levels falsely have to look at CRP and Sed Rate
145
B12 Level Lab Values
Normal 280 - 1500 pg/mL
146
Folate
Lab Values
Normal 3-13 ng/mL
147
Retic count Lab Values
Normal 0.5 - 1.5% Immature RBC
148
Iron Deficiency Anemia
HYPOCHROMIC - MICROCYTIC Increased TIBC, low MCV, low MCH, low MCHC, low iron, decreased ferritin. Inadequate iron supply for hemoglobin production. Iron intake or blood loss Problems with iron absorption
149
Most common nutritional deficiency in the world. Women of childbearing age, Children \<2yo, elderly
Iron Deficiency Anemia
150
S/S Iron Deficiency Anemia
Cyanosis of sclera Brittle nails Koilonychia - spoon shaped nails Confusion - memory loss in elderly HA, pallor, fatigue, weakness, dyspnea, palpitations
151
Vitamin B12-(Pernicious anemia)Folic Acid Deficiency (B9)
MACROCYTIC - NORMOCHROMIC Impaired DNA synthesis causes large developing cells. B12-lack of intrinsic factor Folate deficiency - dietary, alcoholism, cirrhosis High MCV, MCH, MCHC Normal Iron Low B12 Low Folate Low Retic count
152
Vitamin B12-Folic Acid Deficiency S/S
Fatigue Glossitis (inflammation of the tongue) Peripheral neuropathy - paresthesia Dx. CBC, Serum B12 and Folate levels Iron studies (will be normal), Anti-intrinsic factor (to find out if you have antibodies to intrinsic factor shutting it down
153
Anemia of Chronic Disease/Inflammation (2nd most common anemia)
NORMOCYTIC Caused by chronic diseases or inflammation Decreased RBC production by bone marrow Shortening of RBC survival Mechanisms underlying ACD Underlying disease as cause for clinical manifestations (Cancer)
154
Anemia of Chronic Disease/Inflammation Diagnosis
Mild/Mod anemia (Low Hgb/Hct) Low iron, low reticulocyte count, elevated inflammatory markers (sed rate and CRP), low transferrin saturation
155
Aplastic Anemia
Rare but serious Failure of bone marrow to produce cells - stem cell disorder. ALL LAB VALUES WILL BE LOW Leads to pancytopenia (leukopenia, erythrocytopenia, thrombocytopenia) Causes: Autoimmune (SLE, RA), chemo/radiation, viruses (EBV, CMV, HIV, Parvovirus), toxins, cancers Diagnosis: Bone marrow bx
156
RBC destruction anemia Hemolytic anemia
RBC destruction in intravascular or extravascular space DIC, Transfusion Reactions, Thalassemia Hemolytic anemias - genetic - sickle cells, G6PD, autoimmune, infectious - malaria, idiopathic
157
Thalassemia Anemia
MICROCYTIC Hereditary type of Hemolytic anemia. Abnormal hemoglobin for the abnormal quantity of one or two protein chains. Dx Positive family hx, low MCV, MCH, low Hgb/Hct, serum hemoglobin electrophoresis IRON LEVELS ARE NORMAL
158
Beta Thalassemia
Mutation of HBB gene more common, categorized by severity of symptoms S/S: minor fatigue, pallor Mediterranean ethnicity, Middle East
159
Alpha Thalassemia
Mutation in HBA1 and HBA2 genes, Not common S/S: Splenomegaly African American ethnicity
160
G6PD Deficiency
A genetic disorder resulting in RBC membrane destruction Triggered by drugs (sulfa and quinolones) or infection. Affects males of African descent, X-linked recessive (males only) gene
161
Etiology B12 deficiency
Inadequate intake - Vegan diet Inadequate absorption - Pernicious anemia (loss of intrinsic factor) Decreased utilization Use of certain drugs (metformin, antacids)
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S/S B12 deficiency
Neurologic deficits, slow insidious onset, smooth, sore tongue, normal folate, High HC MA
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Etiology Folic acid (B-9) deficiency
Alcoholism, overcooking food. Malabsorption, inadequate intake, parasitic infection, pregnancy
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S/S Folate deficiency
Same as B12 deficiency but NO NEUROLOGIC SYMPTOMS
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Identify the major causes of hemolytic anemias
Genetics - Sickle Cell, G6PD, Thalassemia, Autoimmune, Infectious (malaria), Idiopathic
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Pathology - Sickle Cell Disease and Dx
* Abnormality in genes coding for globin portion of hemoglobin
* Mutation of the HBB gene Inheritance of hemoglobin S from both parents
* Dx hemoglobin electrophoresis
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Clinical manifestations of Sickle Cell disease
Significant anemia, pain, fatigue, irritability, pallor, jaundice from hemolysis Ischemia and necrosis (does not have reverse deformability, they get stuck)
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What factors can cause sickling in sickle cell patients
High intensity, exercise, high altitudes, dehydration
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What factors can precipitate hemolysis seen in G6PD?
Sulfa and quinolones (Cipro) or infection
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Define the pathogenesis of Polycythemia
An abnormal increase in erythrocytes and hemoglobin in the circulation can result in thick blood retarded flow and an increased risk of clot formation w/in the circulatory system
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Primary Polycythemia (Polycythemia vera) Etiology
Neoplastic bone marrow produces too many blood cells due to mutation in the JAK2 gene (Men, Caucasian, Older)
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Primary Polycythemia (Polycythemia vera)
Clin. Man
The absolute increase in RBC mass, leukocytosis, thrombocytosis, increased URIC ACID. Polycythemia vera is a panmyelosis because of elevations of all 3 peripheral blood components Hypertension & Splenomegaly Pruritus after contact with water Headache, erythematous palms, and soles GOUTY arthritis Vasomotor and microvascular thrombotic changes At risk for CVA, Stroke
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Relative Polycythemia (Polycythemia versa)
Increase in hemoglobin due to reduced plasma volume without an increase in red blood cell mass (dehydration)
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Secondary Polycythemia
Caused by factors other than an abnormal clone of erythroid progenitors. is the overproduction of red blood cells. It causes your blood to thicken, which increases the risk of a stroke. It's a rare condition
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Triggers or causes of Secondary Polycythemia
Response to chronic hypoxemia, which triggers the increased production of erythropoietin by the kidneys. Obstructive sleep apnea, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease (COPD).
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Pathophysiology of Clinical manifestations of Primary Polycythemia (Polycythemia Vera)
Theories include histamine release along with other cytokines or cool water contact causing vasoconstriction with prostaglandin and platelet aggregation
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Pathogenesis of iron overload (hemochromatosis)
Saturation of transferrin Iron binding to other proteins. Absorbed by cells that transform iron into reactive oxygen species in the liver, heart, pancreas, and joints. Chronic hepatitis causes increased ferritin and release of iron causing overload
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Hemostasis
HEMOSTASIS -The ability to stop small vessel bleeding after blood vessel injury Involves interaction with the vessel wall, circulating platelets (thrombocytes), and plasma coagulation proteins
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Fibrinolysis
FIBRINOLYSIS - lysis of fibrin to break down the clot. Factor XII and thrombin release plasminogen activators to form plasmin. Plasmin digests fibrinogen and fibrin and inactivates factors V and VIII. Protein S assists protein C in binding phospholipase and stimulates tissue plasminogen activation, initiating fibrinolysis
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The normal process for hemostasis
1. Interaction between platelets and the endothelium of the injured vessel
2. Vascular spasm
3. Platelet aggregation to the endothelium
4. Platelet plug formation (within 15 seconds)
5. Clot formation
6. Clot retraction
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Secondary hemostasis
Formation of fibrin clot through intrinsic and extrinsic pathways of coagulation. Final stage is clot retraction
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Clotting Factors
1. Fibrinogen II
2. Prothrombin III
3. Tissue Factor IV
4. Calcium V
5. Proaccelerin VI
6. Proconvertin VIII
7. Antihemophilic factor IX
8. Plasma thromboplastin X
9. Stuart Prower XI
10. Plasma thromboplastin antecedent XII
11. Hageman factor XIII
12. Fibrin stabilizing factor
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All clotting factor is made in the liver except
Factors 8 and 13 are not made in the liver
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What factors need Vitamin K
2, 7, 9, 10
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Where can you find Vit K in your diet?
Fat-soluble vitamin
Found in green leafy, cheese, butter
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What is needed in all but two steps of the cascade?
Factor IV Calcium
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What factor is associated with Hemophilia
Factor VIII
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What factor co-circulates with factor VIII to cause platelets to adhere?
Von Willebrand Factor
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How are the clotting factors numbered?
By order of discovery
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All factors are synthesized by the liver except
Factor VIII
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Differentiate between the intrinsic and extrinsic clotting pathway
The intrinsic pathway is initiated when blood comes into contact with altered vascular endothelium (inside the vessel) (PTT 33-45 sec - Play table tennis inside the house) Extrinsic pathway begins when the vascular wall is traumatized (PT 10-14 sec- Play tennis outside the house) Intrinsic and Extrinsic pathways lead to the common final pathway for clot formation
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PTT
Normal 33-45 seconds. Partial thromboplastin time used to evaluate the **_INTRINSIC_**, to common pathway **_XII to I_**. **_Used for managing Heparin infusion doses_**
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PT
Normal 10-14 seconds Prothrombin time is used to evaluate the **_EXTRINSIC_** pathway except for tissue factor (III)
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What Leukocytes are considered Granulocytes
Neutrophils Eosinophils Basophils
**_N_**ever**_E_**at**_B_**ananas
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Immature Macrophage
Monocytes
196
Immature Mast cell
Basophil
197
Immature Neutrophils
Bands
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Basophils transfer into what once they are in connective tissue
Basophils in connective tissue are Mast cells and can identify allergins with IgE receptors quickly
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What WBC has C3b receptors for antigens that have been opsonized
Macrophages
200
Patients with platelets \< 20,000
Petechiae Bruising Bleeding gums Occult hematuria Retinal Hemorrhages
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Classical Hodgkins Lymphoma
Painless lymph nodes **_Reed Sternberg Cells_** Abnormal B lymphocytes Adults 20-4- years old Males \> 55
85% - 5 yr survival rate
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3 types of B-Cell, T-Cell and NK-Cell Lymphoma
Aggressive: Diffuse lymphoma, Large B-cell, Burkitt Rapidly progress, Rapid mass growth Fever, Lymphadenopathy, night sweats, fatigue Indolent types: Follicular lymphoma, lymphadenopathy, hepatosplenomegaly Unorganized metastasis: everywhere
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Clinical manifestations of multiple myeloma
CRAB
## Footnote
* Hypercalcemia
* Renal Failure
* Anemia
* Bone lesions Bone pain Increased infections (suppressed B cells)
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When would you see Bence Jones Proteinuria and Lytic Lesions
Multiple Myeloma dx with Serum Protein Electrophoresis
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Two cell types of leukemia
Myeloid and Lymphoid
Myeloid - Adults
Lymphoid - Children
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How to diagnosis Chronic Leukemias
Routine blood count – Lymphocytosis, granulocytosis, monocytosis Peripheral smear Bone marrow biopsy - Blast stage \>20% blast cells
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2 plasma proteins
Albumin and globulins
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What is the benefit of reverse deformability?
RBC can fit into tiny capillaries
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Transferrin
Carries and moves iron from the plasma into the cell
Uber for iron
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Where is RBC's phagocytized?
Spleen
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Relative Anemia
Dilutional effect with normal cell numbers IV fluids, Pregnancy
212
Absolute Anemia
Cell numbers are actually decreased
213
How does the body compensate for anemia?
Tachycardia to increase cardiac output to vital organs. Increased erythropoietin activity in the kidneys
214
Anemias resulting from destruction or dysfunction of RBCs
* Thalassemia
* Sickle Cell
* G6PD
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MCV
Normal 80-94
Volume or size of RBC (Microcytic/Macrocytic)
216
MCH
Normal 27-31
Color of RBC
(Normochromic/Hypochromi)
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What pts are at risk for polycythemia
* COPD
* Chronic lung disease
* High Altitudes
218
Intrinsic and Extrinsic clotting factors meet at what factor to work together
X - 10 then both use V, II, I
219
Examples of endogenous anticoagulants
1. **Antithrombin III - inactivates thrombin**
2. **Protein C & Protein S - both inactivates Factor V & Factor VIII**
3. **Heparin = binds to ATIII**
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Aspirin and Ibuprofen affect only:
Bleeding time
221
D- Dimer
(\<200 ng/ml) assess **clot formation**
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Thrombocytopenia Manifestations
Absent until platelets \<100,000
## Footnote
* Petechiae and purpura at \<50,000
* Deep tissue bleeding and intracranial bleed at \<20,000
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The function of
Antithrombin III
Inactivates Thrombin
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What Factors are associate with the Triad of Virchow
Injury to the blood vessel endothelium
Abnormalities in blood flow
Hypercoagulability of blood
ALL lead to a state of **increased coagulation** this is seen in patients with **PVD**
225
What clotting factor is associated with
**HEMOPHILIA A (Classic)**
## Footnote
**Factor VIII**
**Factor 8**
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Function of
Protein C & Protein S
Inactivates Factor 5 & 8
227
Function of Heparin as an endogenous anticoagulant
Binds to AT III
228
Peripheral Smear
Morphologic characteristics of platelet function
229
How long do Aspirin and Ibuprofen affect platelet function?
Aspirin affects platelets for their life span
Platelets normalize 24 hours after the last dose of Ibuprofen
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Describe the different conditions associated with thrombocytopenia
* Leukemia and other cancers
* Some types of anemia
* Viral infections, such as hepatitis C or HIV
* Chemotherapy drugs and radiation therapy
* Heavy alcohol consumption
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ITP
Immune Thrombocytopenic Purpura
Hypocoagulopathy state, when the immune system is destroying its own platelets
Secondary ITP causes: Autoimmune diseases, immunizations from live vaccine, infections, cancer
Autoantibody medicated development: IgG
Primary ITP: Most common cause
Acute: children 2-4 yo
Chronic: 20-50 yo women \>men
232
Common Manifestations
of ITP
Often asymptomatic
Abnormal bleeding - Petechiae/Purpura
Epistaxis, excessive bruising, Gi/rectal, menses
Diag made by exclusion
233
TTP
Thrombotic Thrombocytopenic Purpura
In TTP damage to microvasculature and/or genetic predisposition can lead to plasma aggregation and thrombus formation. The platelet aggregation causes thrombocytopenia. The microvascular occlusion results in widespread ischemia to organs, presenting as fever, purpura, altered mental status, neurological signs, renal dysfx.
Often occurs as a result of *_deficiency_* in **_ADAMT513 enzyme_**
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Pathogenesis of
Von Willebrand Disease
Most common hereditary bleeding disorder
Deficient or absent VW factor
3 genetic types 1 acquired
Decreased VWF and **Factor VIII (8)**
* Prolonged bleeding time & Prolonged PTT*
* Normal platelet count & Normal PT/INR*
235
Protein C Deficiency
Cerebral & ophthalmic thrombosis
Renal vein & umbilical thrombosis
Does not activate Factor V and VIII
236
Protein S Deficiency
Autosomal dominant
Deep vein thrombosis and pulmonary emboli
Does not activate Factor V and VIII
237
Factor V Leiden
Inherited
Genetic mutation that will not allow Factor V to be inactivated
Joint Intrinsic & Extrinsic pathway issue
238
Converts Prothrombin to Thrombin & is the common pathway for Intrinsic and Extrinsic pathway
X
239
Natural Active Immunity
Had the disease
240
Artificial Active Immunity
Got Vaccinated
241
Natural Passive Immunity
Mother gives to the infant in breast milk
242
Artificial Passive Immunity
Giving you immune globulin or gamma globulin
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