Exam 3- Patho

Hematopoiesis: process of blood cell production

All blood cells arise from a small number of underdeveloped, precursor cells called pluripotent stem cells in the bone marrow

Erythropoiesis

• Development of RBCs

• Erythrocytes are derived from erythroblasts (normoblasts)

• Maturation is stimulated by erythropoietin 

• Each step HgB increases + nucleus decreases in size

• 120-day life cycle

• Substances needed for synthesis of healthy RBCs- protein, iron, Vit B12, folic acid

  • Iron is the main nutritional element needed for HgB synthesis

• Hypoxia stimulates the kidney to release erythropoietin (EPO)

• EPO stimulates bone marrow to synthesize RBCs 

• Volume of circulating RBCs in healthy individuals remain constant 

The spleen

• A highly vascular organ, the “graveyard of RBCs” + an organ of immunity 

  • ⭐️In spleen, RBCs are broken down into component parts which are recycled to make NEW RBCs

  • Spleen is a secondary lymphoid organ containing lymphocytes + resident macrophages 

• It isolates abnormally shaped + hemolyzed RBCs and destroys them 

• Splenomegaly occurs when there’s a large amnt of RBC breakdown occurring

• If spleen is unable/absnet, Kupffer cells remove older RBCs in liver 

Anemia

• Reduction in total number of erythrocytes in circulating blood or in the quality/quantity of HgB

• Insufficient delivery of oxygen → tissues

  • Impaired erythrocyte production (Bone marrow dysfunction, lack of nutrients- iron, folate, B12)

  • Acute or chronic blood loss

  • Increased erythrocyte destruction (hemolysis)

  • Combination of above 

• Women more likely to have anemia bc of menstrual cycle

Classifications of Anemia

• Etiology

• Morphology- Size ; Identified by terms then end in -cytic 

  • Macrocytic, microcytic, normocytic

• HgB content; Identified by terms that end in -chromic 

  • Normocytic + hypochromic 

Microcytic hypochromic Anemia

Disorders of HgB synthesis (iron deficiency) 

Macrocytic Anemia

arise from abnormalities that hinder maturation of erythroid precursors in bone marrow

Normocytic–Normochromic Anemia

shape of RBCs help determine cause

• Ex: sickle cell anemia

Complete Blood Count

• MCV (mean corpuscular volume)- size of RBC 

• MCH (mean corpuscular HgB)- color of RBC 

• MCHC (mean corpuscular HgB concentration)- concentration of RBC

Compensatory mechanisms of Anemia (3)

1) Heart rate increased

2) Cardiovascular

3) Capillary dilation

Macrocytic-Normocytic (Megaloblastic) Anemias: Pernicious

Etiology: Congenital/acquired deficiency of intrinsic factor (IF)- in stomach lining

Mechanism: Insufficient influence of Vit B12 on developing cells bc of deficient IF; Abnormal DNA + RNA synthesis; Premature cell death

Vitamin B12 + Neuro Effects

• Vit B12 deficiency myelin defects + abnormal neural conduction occur mainly in dorsal horns + corticospinal tract of spinal cord called subacute combined degeneration, manifested as numbness + weakness in extremities (paresthesia) and gait disturbance 

• Synthesis of serotonin, norepinephrine, and dopamine are affected which is relevant to cognitive changes, such as confusion + memory loss

Iron deficiency Anemia (IDA) Highest risks/problems / who is it found in

• Highest risk: toddlers, adolescent girls, women of childbearing age, those living in poverty, infants consuming cow’s milk, older adults on restrictive diets, teenagers on junk food diets

• Causes: dietary lack + eating disorders, impaired absorption, increased requirement, chronic blood loss, medications (cause GI bleeding, some surgeries)

• Particularly in males and postmenopausal women, due to chronic blood loss from GI bleeding

Fecal occult blood testing (FOBT) recommended w/ Anemia patients for what

To rule out GI Bleeding + potential colon cancer

What is an essential element of Hgb synthesis

Iron- body maintains balance between iron in use for Hgb + iron stored available for future Hgb synthesis

IDA specific signs:

• Hair loss, cheilitis, glossitis, nail changes (koilonychia), cold/numb fingertips

• ⭐️‬‭Pica- craving for nonfood substances such as ice, clay, starch, chalk, dirt/other material

Normo-Normochromic Anemias:

Sickle Cell Anemia:  autosomal recessive disease

• Causes structural fragility of the sickle cell anemias RBCs, upon exposure to hypoxia/stress, the RBC contorts into a sickle shape

Vaso-Occlusive Crises in Sickle Cell Anemia

• Sickled RBCs cannot pass thru capillaries

• Become trapped, blocking blood flow + creating ischemia + consequent tissue hypoxia, leads to organ damage + possible infarction

• Episodes of ischemia are painful vaso-occlusive crises

  • Chest, abdomen, long bones, and joints affected. Multiple sites often involved simultaneously

    Splenic dysfunction occurs bc of excess RBC death

Myeloproliferative RBC Disorders

Polycythemia- overproduction of red blood cells

Types of Polycythemia (2)

• Relative Polycythemia- results of dehydration

  • Fluid loss results in relative increases of RBC counts + Hgb + Hct values

    • Minor consequences, resolved w/ fluid admin. + treatment

• Absolute Polycythemia- 

  • Primary (polycythemia vera): hyperproliferation of all blood cells; abnormality of stem cells in bone marrow

  • Secondary (erythrocytosis): increase in erythropoietin as normal response to chronic hypoxia/ inappropriate response to erythropoietin-secreting tumors

Composition of blood: Leukocytes

(WBCs)- defend body against infection + remove debris

Composition of blood: Granulocytes

Membrane-bound granules in their cytoplasm; Granules contain enzymes capable of destroying microorganisms; Inflammatory + immune func.

1. Neutrophils- phagocytes in early inflammation

2. Eosinophils- ingest antigen-antibody complexes; induced by IgE hypersensitivity; increase in parasitic infections

3. Basophils- structurally + functionally similar to mast cells

Composition of blood: Agranulocytes

• Monocytes: immature macrophages

• Macrophages: in tissues

• Lymphocytes: mature to T cells, B cells, plasma cells 

• Natural Killer Cells

Composition of blood: Platelets

Essential for blood coagulation + control of bleeding

• Disk-shaped cytoplasmic fragments

Infectious Mononucleosis / Caused by?

• Mono/kissing disease

• Acute, self-limiting infection of B lymphocytes transmitted by saliva thru personal contact 

• Caused by Epstein-Barr virus (EBV)- 85% 

  • B cells have EBV receptor site 

  • Other: CMV, hepatitis, influenza, HIV

Symptoms: fever, sore throat, swollen cervical lymph nodes, increased lymphocyte count, atypical lymphocytes

Hematologic Neoplasms + 2 main characteristics

• Types of cancer that affect blood, bone marrow, and lymph nodes

• Either located in blood (leukemia) or lymph nodes (lymphoma)

  1) ⭐️Cancerous WBCs proliferate uncontrollably, leading to overcrowding 

  • Leukemia primarily occurs in bone marrow

  • Lymphoma affects lymphoid tissues such as lymph nodes

  2) ‭‭⭐️Genetic susceptibility to mutagens often factor in both 

  • Leukemia- excess cancerous WBCs suppress normal blood cell development in bone marrow 

  • Lymphoma- cancerous WBCs primarily affect lymphatic system

Clinical manifestations of Hematologic Cancer (symptoms/what physical exam reveals)

• Symptoms include:

  • ⭐️Anemia (fatigue, weakness, pallor)

  • ⭐️Leukopenia (increased susceptibility to infection)

  • ⭐️Thrombocytopenia (increased susceptibility to bleeding + bruising)

  • ⭐️Bone pain (bc of proliferating cancerous blood cells putting pressure in bone marrow)

• Physical exam may reveal enlarged lymph nodes, splenomegaly, or both

  • Enlarged lymph node from proliferative neoplastic cells

  • Splenomegaly result of excessive infiltration of neoplastic blood cells /excessive hemolysis by overactive spleen

Leukemia

• Uncontrolled proliferation of malignant leukocytes causing overcrowding of bone marrow and decreased production + function of normal hematopoietic cells 

• Classification based on 

  • Predominant cell of origin- myeloid or lymphoid 

  • Degree of differentiation that took place before cell became malignant

    • Acute with rapid growth of immature (blast) cells

    • Chronic with slow growth of more differentiated cell

Acute Lymphocytic Leukemia (ALL)

Rapid, >30% lymphoblasts + B cells

Chronic Lymphocytic Leukemia (CLL)

Slow; Monoclonal B

Acute Myeloid Leukemia (AML)

Rapid; precursor myeloid cells

Chronic Myelogenous Leukemia (CML)

Slow; neutrophilic/eosonphilic/clonal; arise from hematopoietic stem cells

Lymphadenopathy

• Enlarged lymph nodes that become palpable + tender

• During infection, macrophages + lymphocytes are proliferating

Local lymphadenopathy

drainage of inflammatory lesion located near the enlarged node

General lymphadenopathy

occurs in presence of malignant/nonmalignant disease

Lymphoma- Hodgkin

Nodal involvement

Extranodal movement

Spread

Fever, night sweats, weight loss

Reed Sternberg cells

Extent of disease

Localized to single axial group of nodes

Rare

Orderly spread

Common

Present

Often localized

Lymphoma- Non-Hodgkin

Nodal involvement

Extranodal movement

Spread

Fever, night sweats, weight loss

Reed Sternberg cells

Extent of disease

Multiple peripheral nodes

Common

Non Contagious

Uncommon

Not present

Rarely localized

Burkitt Lymphoma

• Highly aggressive B-cell non-Hodgkin lymphoma 

• Very fast growing tumor of the jaw + facial bones (Africa); rare in US

• EBV more than 90% of cases

• Abdominal swelling for people affected in US

• Biopsy/bone marrow findings

Multiple Myeloma: Arise where/ what does it produce

• Arises in B lymphocytes, causing proliferation of abnormal plasma cells in bone marrow 

• Malignant plasma cells produce abnormally large amounts of one class of immunoglobulin (M protein: abnormal antibody molecule)

Multiple Myeloma: Causes

• Cause bone destruction, bone marrow failure, renal failure, neurological complications, amyloidosis 

• Bone pain, especially in back common (result of lytic destruction + formation of plasmacytomas)

• Lytic lesions are rounded, punched-out areas of bone found in vertebra, skull, ribs, humerus, and femur

Platelets: Thrombocytopenia what does it cause?

Low number of platelets

• <100,000/uL (can cause bleeding)

• Prolongation of normal clotting may result

• If <20,000, spontaneous bleeding may occur

Platelets: Thrombocytosis what does it cause?

• >750,000/uL (can cause excessive clotting)

• Risk for spontaneous blood clots (thrombosis), stroke, <3 attack increases

Platelet formation stimulated by…, sythesized by the …

Thrombopoietin; liver

Thrombocythemia (Cause/Types/Causes)

Too much platelet count

• Cause: accelerated platelet production in bone marrow

• Types: primary/secondary (reactive)

• Causes: intravascular clot formation (thrombosis), hemorrhage, other

Essential (primary) thrombocytopenia (ET)

• ⭐️Chronic myeloproliferative disorder

• Characterized by excessive platelet production, resulting from a defect in megakaryocyte progenitor cells 

• ⭐️Clinical: microvascular thrombosis, erythromelalgia, possible bleeding

Distribution of Body fluids

• Total body water (TBW)

  • Intracellular fluid (ICF)- ⅔ of TBW

  • Extracellular fluid (ECF) ⅓ of TBW

    • Interstitial fluid (ISF), Intravascular fluid (blood plasma), Lymph, synovial, intestinal, CSF, sweat, urine, pleural, peritoneal, pericardial, and intraocular fluids

Distribution of Body fluids: Peds + 2 examples of decreased TBW

• Peds: 70-80% of body weight; susceptible to significant changes in body fluids

• ️Aging: decreased % of TBW

  1) Increased fat mass + Decreased muscle mass

  2) Renal decline; diminished thirst perception

• Obesity: less TBW because fat is water repelling!

Water Movement Between Fluid Compartments (Osmosis )

How water moves btwn ICF and ECF compartments

Water Movement Between Fluid Compartments (Osmolality)

Concentration of solutes per kg of fluid

• Water crosses cell membranes freely so osmolality of TBW normally equilibrium

Water Movement Between Fluid Compartments (Law of Osmosis)

Water moves from area of lower solute concentration to areas of higher solute concentration to balance solute levels across a semipermeable membrane 

Water Movement Between Fluid Compartments (Osmotic forces/2 Types)

Osmotic forces: pressure exerted by solutes in solution

1. Sodium for ECF

2. Potassium for ICF

Fluid Homeostasis Maintained by:

Osmoreceptors in the hypothalamus- respond changes in blood osmolarity + blood fluid volume

1. Sensation of thirst at hypothalamus

2. Antidiuretic hormone (ADH, arginine vasopressin)

3. Renin-angiotensin-aldosterone system (RAAS)

4. Natriuretic hormones-excretion of both Na+ and H2O by kidneys in response to excess ECF volume

Edema + Causes

Accumulation of fluid within interstitial spaces

• Causes:

  • Increase in hydrostatic pressure

  • Decrease in oncotic pressure

    • Oncotic pressure- force exerted by albumin in bloodstream

  • Increase in capillary permeability

  • Lymph obstruction (lymphedema)

• Localized vs generalized 

• Pitting edema

Acid-Base Balance

• Carefully regulated to maintain normal pH via multiple mechanisms

• pH: negative logarithm of H+ concentration

• Acids are formed as end products of protein, carb, and fat metabolism

• To maintain body’s normal pH (7.35-7.45) H+ must be neutralized/excreted

• Bones, lungs, kidneys= major organs involved in regulation of acid-base balance

Buffering Systems - Whats buffer? Most important plasma buffering systems?

• Buffer is a chemical that can bind excessive H+/OH- w/o significant change in pH

• Most important plasma buffering systems= Carbonic Acid, Bicarb, Hgb

• Carbonic Acid-Bicarb Buffering

Buffering Systems - Where does it operate?

• Operates in lung and kidney *

• Greater the PaCO2, the more carbonic acid is formed

• At pH of 7.4, ratio of bicarb-carbonic acid is 20:1

Carbonic Acid-Bicarbonate Buffering

• Lungs can decrease carbonic acid

• Kidneys reabsorb/regenerate bicarb but do not act as fast as lungs

Carbonic Acid-Bicarbonate Buffering: If bicarb decreases…. + explain compensation

…Then pH decreases, causes acidosis

• pH can be returned to normal if carbonic acid also decreases (aka compensation)

Carbonic Acid-Bicarbonate Buffering: Respiratory compensates by…

… increasing ventilation to expire CO2 (acidosis) or by decreasing ventilation to retain carbon dioxide (alkalosis)

Carbonic Acid-Bicarbonate Buffering: Renal system compensates by…

Producing acidic/alkaline urine (kidneys)

Protein buffering (+2 types)

• Proteins carry negative charges, allow them to bind w/ H+ and act as buffers

  • Intracellular buffering: Hgb serves as primary buffer, helping to maintain pH by binding with excess H+  

  • Plasma buffering: while Bicarb is the major plasma buffer, proteins (Hgb + albumin) contribute to buffering in bloodstream

Cellular ion exchange

Exchanges of K+ for H+ in acidosis + alkalosis

• Acute acidosis accompanied by hyperkalemia

Acid-Base Imbalances (normal pH + Pressure + Acidosis/Alkalosis)

Normal arterial blood pH: 7.35-7.45

• Obtained by arterial blood gas (ABG) sampling (pressure of gases in bloodstream)

• PaO2: pressure of oxygen in arterial blood (80-100 mm Hg)

• PaCO2: pressure of carbon dioxide in arterial blood (35-45 mm Hg)

• HCO3-: amnt of bicarb in the blood (22-26 mEq/liter)

• SaO2: saturation of Hgb with oxygen (95-100%)

Acidosis: systemic increase in H+ concentration / decrease in bicarbonate (base)

Alkalosis: systemic decrease in H+ concentration / increase in bicarbonate

Respiratory Acidosis: Etiology

Failure of respiratory system to remove/exhale CO2 from body fluids as fast as it is produced by cells- excess of CO2 in blood (hypercapnia)

Respiratory Acidosis: Caused by

Caused by any interference with breathing (COPD, respiratory muscle weakness/paralysis, brainstem trauma, over-sedation)

Respiratory Acidosis: Compensation

Kidneys attempt to REABSORB BICARB and EXCRETE H+ 

Respiratory Alkalosis: Etiology

Loss of CO2 from lungs faster than it is produced by cells; can be breathing too fast; hypocapnia 

Respiratory Alkalosis: Caused by

High altitudes, hypermetabolic states, early salicylate intoxication, anxiety or panic disorder, improper use of mechanical ventilators

Respiratory Alkalosis: Compensation

Kidneys attempt to REABSORB max H+ and EXCRETE BICARB

Metabolic acidosis: Etiology

Abnormal accumulation of non carbonic acids/abnormal loss of bases

Metabolic acidosis: Occur in.. / Clinical…

Occur in: lactic acidosis, diabetic ketoacidosis, renal failure causing acid buildup, diarrhea or vomiting with loss of bicarb

Clinical: Headache, lethargy, Kussmaul’s breathing (deep rapid respirations)

Metabolic acidosis: Compensation

Hyperventilation and renal excretion of excess acid

Metabolic Alkalosis: Etiology

Bicarb concentration increased, from loss of metabolic acids (Cl-)

Metabolic Alkalosis: Caused by

Vomiting, gastric suctioning, excessive bicarb intake, hyperaldosteronism w/ hypokalemia, diuretic therapy

Metabolic Alkalosis: Compensation

Hypoventilation, the lungs retain CO2

Overview of Electrolytes

• Electrolytes are in both ECF + ICF compartments but different concentrations

• All electrolytes move across compartments but must be in balance for health

Overview of Electrolytes: Intracellular

Cation

• ⭐️Potassium (K+)

• Magnesium (Mg)

• Calcium (Ca+)

Anion

• Phosphate (HPO-)

Overview of Electrolytes: Extracellular

Cation

• ⭐️Sodium (Na+)

• Calcium (Ca+)

Anion

• Chloride (Cl-)

• Bicarbonate (HCO3-)

Isotonic alterations

• TBW change with proportional electrolyte change 

• Isotonic fluid loss (dehydration + hypovolemia)

• Isotonic fluid excess (hypervolemia)

Isotonic (isoosmolar imbalance) Mechanism?

Gain/loss of ECF resulting in concentration = 0.9% sodium chloride (salt) solution (normal saline); no shrinking or swelling of cells

Hypertonic (hyperosmolar imbalance) Mechanism?

Imbalance that results in an ECF >0.9% salt solution, water loss/solute gain; cells shrink

Hypotonic (hypoosmolar imbalance Mechanism?

Imbalance that results in an ECF <0.9% salt solution; water gain/solute loss; cells swell

Hypertonic alterations (definition + causes)

Hypernatremia- related to sodium (Na+) gain / water loss

• ⭐️Inadequate free water intake, inappropriate administration of hypertonic saline solution, oversecretion of aldosterone, decreased ADH secretion (diabetes insipidus), Cushing's syndrome

Water movement from ICF to the ECF - intracellular dehydration 

Manifestations: seizures, muscle twitching, hyperreflexia

What is potassium essential for

Transmission + conduction of nerve impulses, normal cardiac rhythms, and skeletal + smooth muscle contraction

What does potassium regulate

ICF osmolality + deposits glycogen in liver + skeletal muscle

What regulates potassium balance?

⭐️Kidneys, aldosterone, and insulin secretion, and changes in pH regulate K+balance

• Insulin promotes uptake of K+ by stimulation the Na+, K+, ATPase pump, facilitating the movement of K+ into the liver and muscle cells along with glucose, which helps regulate blood glucose levels after eating 

Calcium + Phosphate; what are they controlled by?

1. PTH: increases plasma calcium levels via kidney reabsorption 

2. Vit D: fat-soluble steroid; increases calcium absorption from GI tract

3. Calcitonin: Decreases plasma calcium levels

Hypocalcemia (causes + manifestations)

• Calcium lower than 9.0 mg/dL / ionized levels lower than 5.5

• Causes: inadequate intestinal absorption, decreases in PTH + Vit D, blood transfusions 

• Manifestations

  • Increased neuromuscular excitability (partial depolarization)

  • Muscle spasms (partially in hands, feet, facial muscles), Chvostek + Trousseau signs, convulsions, tetany 

Theories of pain (4)

• Specificity pain: amount of pain related to the amount of a tissue injury 

  • Accounts for many types of injuries, does not explain psychologic contributions to pain/chronic pain 

• Pattern theory: describes roles of nerve impulses interpreted by CNS 

  • Does not account for all pain experiences

• Gate control theory: explains complexities of the pain phenomenon

  • Pain is modulated by a “gate” in the cells of the substantia in the spinal cord

• Neuromatrix theory (expands on gate control theory)

  • Brain produces patterns of nerve impulses drawn from various inputs including genetic, psychologic, and cognitive experiences 

  • Illustrates plasticity (the adaptable change in structure + function) of the brain

  • Sensory inputs to the brain produce patterns of pain, but stimuli may independently originate in the brain with no external input

Pain is modulated by a “gate” in the cells of the ______ in the spinal cord

substantia

Describe the fibers that either block/allow pain signals to reach the brain

• Large myelinated A-delta fibers + small unmyelinated C fibers respond to a broad range of painful stimuli, such as mechanical, thermal, and chemical. These nociceptive transmissions open the gate. 

• Stimuli from nonnociceptive transmissions, such as touch and larger A-beta fibers close the gate

Neuroanatomy of pain: Afferent Neurons/ Interpretive centers/ Efferent neurons

1. Afferent neurons: sensory nerves

   • Begin in PNS, travel to spinal gate in dorsal horn, then ascend to higher centers in the CNS (primarily via spinothalamic tract)

   • Carry temp, touch, proprioception, vibration, and pressure sensations into the spinal cord 

2. Interpretive centers

   • Located in brainstem, midbrain, diencephalon, and cerebral cortex

3. Efferent neurons: motor nerves

   • Descend from CNS to the dorsal horn of the spinal cord, with corticospinal tract contributing to pain modulation through descending pathways from motor cortex

Nociceptors

• Free nerve endings in the afferent PNS that selectively respond to chemical, mechanical and thermal stimuli

• Processing of potentially harmful stimuli

Nociceptors- A-delta fibers/ C fibers

1. A-delta fibers are large and lightly myelinated.

   • Conduct impulses rapidly + cause the first, short-lived acute experience of pain

   • Causes reflex withdrawal of affected body part from stimulus before pain sensation is perceived

2. C fibers are small and unmyelinated

   • Conduct impulses slowly and cause longer lasting, persistent dull, aching, or burning sensations

Neuroanatomy of Pain- Pain threshold/ pain tolerance

• Pain threshold- lowest intensity of pain a person can recognize

  • Intense pain at one location may increase threshold in another location

    • One with many painful sites may only report most painful

    • After dominant pain is diminished, one may identify other painful areas 

• Pain tolerance- Greatest intensity of pain  one can endure 

  • Individualized; varies among people and in the same person over time

Acute pain description

Protective mechanisms

• Immediate sensation after injury; transient 

• Alerts an individual to a condition/experience that’s immediately harmful to body

• Begins suddenly + relieved after pain stimulus is removed; lasts <3 months

Acute Somatic Pain

• Arises from joints, muscle, bone, and skin 

• A-delta fibers: pain is sharp and well localized

• C-fibers: pain is dull, aching, throbbing, and poorly localized

Acute visceral Pain

• Arises from internal organs + lining of body cavities

• Poorly localized as a result of fewer #’s of nociceptors

Referred Pain

• Pain in an area is removed/distant from its point of origin 

• Area of referred pain is supplied by same spinal segment as actual site

• Can be acute/chronic

Chronic pain

No protective purpose

• Prolonged pains sensation after injury has healed (>3-6 mo)

• Caused by dysregulation of nociception + pain modulation processes

• Neuroplasticity: brain’s ability to reorganize itself by forming new neural connects in response to persistent pain signals 

• May be persistent/intermittent; may be sudden/develop insidiously 

• May cause behavioral + psychologic changes, such as depression + anxiety