Anemia, Fever and Temp regulation Flashcards
What is hemoglobin a measure of?
gm/dl; blood HB concentration
What is MCV?
average volume of red cells, mean corpuscular volume, volume of blood x HCT / #RBC
What is MCHC?
mean corpuscular hemoglobin concentration, HB/HCT,
What is reticulocyte count?
number of reticulocytes/total RBC;
What is hematocrit?
MCV x RBC, volume percent of RBC
What is mean corpuscular hemoglobin?
MCH, HB/RBC, concentration of hemoglobin packed in RBC
What is RDW?
red cell distribution width, measure variation in cell size, increased in sickle cell and nutritional deficiencies
What is anisocytosis?
RBC unequal size
What is poikilocytosis?
abnormally shaped
What is polychromasia?
abnormal increase in # of RBC premature in blood
what is hypochromia? How is this determined?
hypopigmentation; pale area more than 1/3 of RBC
What is microcytic? macrocytic? What cell is used for size comparison?
small RBC; large RBC; compare size to WBC
What is microcytic anemia?
Hb is decreased below normal and the MCV less than 80fl, MCHC may or may not be decreased if so hypochromic
What are the three general causes of microcytic anemia?
abnormality in iron metabolism, globin metabolism, and porphyrin metabolism
What are the causes of iron metabolism?
inadequate iron intake, chronic blood loss, and anemia of chronic disease
What are the causes of inadequate iron intake in microcytic anemia?
pediatric age, pregnant moms (iron uptake by fetus, suboptimal stores before pregnancy), otherwise inadequate iron intake in adults rare cause of microcytic anemia
What are the causes of chronic blood loss in microcytic anemia?
most common is GI; GI- ulcer, colon or gastric carcinoma, hiatal hernia, esophageal varices, ulcerative colitis, crohn disease, leiomyoma, salicylate, meckel diverticulum, hookworm, angiodysplasia; Female gential- dysfunctional uterine bleed, endometrial hyperplasia/carcinoma, excessive menses; Pulmonary- carcinoma, chronic infection; Urinary- bladder cancer, chronic infection
What are the causes of anemia of chronic disease? what amount are microcytic? normocytic?
rheumatoid arthiritis and other autoimmune disorders, cancer, chronic infection, severe tissue injury; 30% micro, 70% normo
What are the reasons for anemia of chronic disease?
impaired Fe flow into RBC- hepcidin triggers degrade. iron exporter (ferroportin) thus limiting egress from enterocytes and macrophages (limits Fe for microorganisms), may lead to anemia- infection, malignancy, and inflammation; decreased RBC survival, insufficient erythropoietin to stimulate RBC production
What are the types of thalassemia’s?
inherited, heterogeneous group, alpha and beta chain most common, in minor not anemia but have microcytosis, major= severe anemia
What are the features of Hemeglobin E?
SE Asia, most common globin abnormality, HgbS, beta chain abnormality, homo (marked hypochromia, microcytosis with little or no anemia) and heterozygous
What us serum ferritin? Decreased means? What can falsely increase?
principle storage form of iron; decrease in iron stores; chronic disease, when acute phase reactant increases (surgery, febrile illness, liver cell necrosis), oral or parenteral iron administration
What is iron-binding capacity?
IBC is a reflection of transferrin levels, although transferrin can be directly measured
What are causes of normocytic anemia?
chronic disease (most common), acute blood loss, marrow replacement (myeloplastic anemia), aplastic anemia, renal failure, hemolytic anemia
What are the causes of increased reticulocyte count in normocytic anemia? normal or decreased reticulocyte count?
acute blood loss, hemolytic anemia; anemia of chronic disease, renal failure, aplastic anemia, myelophthisic anemia (marrow replacement by infiltrative disease such as cancer and histoplasmosis)
What are the features of folate or B12 deficiency causing megaloblastic anemia?
maturation pattern in bone marrow, nuclear:cytoplasmic dyssynchrony, especially in RBC series, lab assessmentbegins with folate and B12 levels depending on hist and PE, schilling test- abnormal in B12 deficiency
what are the causes of drug-induced perturbed DNA synthesis?
antineoplastics, immunosuppressive, and antiretroviral
What are the causes of non-megaloblastic macrocytic anemia?
liver disease, hypothyroidism, bone marrow regeneration following blood loss or hemolysis with increased reticulocyte counts, myelophthisic anemia, myeloproliferative disease, multiple myeoloma, some causes of sideroblastic anemia
what neural structures are involved in thermoregulation? Which is the “thermostat”?
hypothalamus and limbic -> <- spinal cord and sympathetic ganglia; hypothalamus (esp. preoptic region, thermosensitive neurons)
What are mechanisms of heat production in the body?
mitochondrial oxidative phosphorylation (ADP->ATP, >50%), skeletal muscles during exercise ~25%, shivering in adult humans, and brown adipose tissue
where is brown adipose tissue located? characteristics? physiological role?
esp. near neck and scapulae; brown, profuse vasculature, numerous mitochondria (uncoupling protein 1, UCP1), thermoregulation in newborns and small mammals, possibly energy metabolism in adults (BAT activity inversely related to BMI)
What is the function of UCP1 in brown fat?
leaky inner membrane, energy released as heat, not stored as ATP, regulated by T3 locally
How is brown fat activated?
adrenergic neuron to B3 adrenergic receptor-> cAMP-> nucleus-> increase UCP1 production-> increase in heat
Where is heat lost? percent for each site?
skin 80-90%, 10% from lung
What is the mechanism for fine adjustment of temperature from hypothalamus?
sense absolute and change in temp of blood, autonomic nerves to skin BV, inc. BV diameter-> inc. heat loss -> dec. body temp OR dec. BV diameter-> dec. heat loss-> inc. body temp
What is the mechanism for coarse adjustment of temperature from hypothalamus?
thermal skin receptors relay to hypothalamus which relays signals; autonomic neurons-> sweating-> dec. body temp OR somatic neurons-> shivering-> inc. body temp
What causes hyperthermia? other name and clinical features?
abnormal thermoregulation; heat stroke- warm dry skin, no sweat, inc. temp, delirium, coma, organ failure, cardiac arrhythmia, death
treatment for hyperthermia? risk groups?
rehydration, immersion in cool bath, not antipyretics; s/p CVA, cord injury, low mobility, low sweating (drugs or skin disorder), and diuretics
what is normal body temp? What is the upper limits of normal?
old- 37C and 98.6F; new- 36.8C or 98.2F (men 98.1, women 98.4), 37.7C or 99.9F
What are some things that cause normal body temperature variation? slight elevation?
normal diurnal variation (circadian T rhythm,0.5C -0.9F, high point 4-6p, low point 2-6a); menstruation, 1st trimester, ovulation, giant meal, hard exercise (1-4 deg), ambient temp >85F)
what are the bodies high->low gradients? Regional variants of temp?
core-> epidermis, thrunk-> extremeties, hand-> fingertips, flexor->extensor surface; heart, brain and GI-37, scrotum 32, fingertips 20-25
How does regional body temp effect infections?
mycobacterium leprae grow best at ~31C (affects ears, nose, fingers and toes), sporothrix grows best at 25C (affects extremities, rarely organs, heat to treat), rhinovirus grows best at 33C (temp of nasopharynx
How does regional temp variation effect rash development?
some spread warm to cool (trunk to extremities, i.e. VZV) some spread cool to warm (extremities to trunk, i.e. rickettsia rickettsi)
What are exogenous pyrogens? How do they work?
microbes or their products, ligands for TLR, stimulate cells to make endogenous pyrogens (macrophage, monocyte, PMNs, glial cells, neurons
What are endogenous pyrogens? How do they work?
cytokines (IL-1beta, IL6, TNF alpha, IFN gamma), work at hypothalamic level- increase cyclooxygenase which increases PGEs-> reset thermostat higher
what role does PGE2 play in fever?
levels high in hypothal and 3rd ventricle, highest near circumventricular organs (network of large capillaries, pyrogen-> endothelial rxn= 1st step), triggers release cAMP-> induces release of monoamine NT, hypotalmic reset up, causes myalgia, arthralgia in peripheral tissues
What are endogenous cryogens? Examples?
affect firing of thermosensitive neurons (help control upper limit of body T), arginine vasopressin, alpha-MSH, neurochem (epi and NE), glucocorticoids and their inducers (CRF, ACTH)
What are acute phase proteins? What effects change in levels?
rise or fall by 25%, altered due to production by hepatocytes; substantial- infection, trauma, surgery, burns, tissue infarction, inflammatory states; moderate- hard exercise, heatstroke, and childbirth; small- psychological stress and psychiatric illness
What are some examples of acute phase proteins?
C-reactive protein, amyloid A, haptoglobin, fibrinogen, and procalcitonin
What are some other acute phase reactions?
neuroendocrine, hematopoietic, and metabolic
What does CRP bind and do?
binds phosphocholine on B and to pahgocytes, activates complement
What is amyloid A, it binds to and does what?
apolipoproteins that bind lipoproteins, inc. adhesion and chemotaxis of phagocytes, ?inflammation in coronary arteries?, 2ndary amyloidosis if chronic
What is haptoglobin? What does it do?
anti-inflammatory antioxidant, aids wound healing
What is fibrinogen? What does it do?
coagulation component, affects rate of RBC fall in plasma (erythrocyte sedmentation rate, ESR, or sed rate)
What is procalcitonin? What does it do?
prohormone (thyroid C cell response to hypercalcemia), inc. w/ B infection (IL1-beta), rises faster than ESR or CRP, falls quick if infection responds to Rx, no increase if viral (PCT sytnh. inhibited by IFN-gamma), biomarker for respiratory infection
What occurs in the neuroendocrine acute phase response?
inc. CRH, ACTH and corticol; inc. adrenal secretion of catecholamines
What occurs in the hematopoietic acute phase response?
anemia of chronic disease, leukocytosis, thrombocytosis
What occurs in the metabolic acute phase response?
dec. muscle and negative nitrogen balance, dec. gluconeogenesis
what are the benefits of fever?
preserved thru evolution (all vertebrates and some invertebrate), prevent fever (inc. death in animals), high temps inihibit B growth (Rx syphilis and gonorrhea), associated cytokines can aid host defense
What are some harmful effects of fever?
seizures (103F or 40C, infants and young kids, prob rate of rise, high fever any age ~105), increased metabolic demands (dec. LV stroke volume and work), loss of brain function (>106F or 41C any age)
What is the host perspective on fever? species perspective?
effect either good or bad; mediates speedy recovery from mild-moderate infection and hastens death of hopelessly infected who pose epidemiologic threat
When and with what do you treat fever?
controversial- probly ok; high fever in very young (prevent seizures or metabolis demands too great; ASA (avoid under 21-Reye’s), acetaminophen, NSAIDS- inhibit COX-> dec. PGE2, 4-6hrs round the clock; steroids- inhibit CO and mRNA for cytokine synthesis
What is the cause and treatment of intermittent fever?
pyogenic abcess, prn ASA; 2 daily spikes- military TB, GC endocarditis, salmonellosis, malaria, visceral leishmaniasis (Kala azar)
What are some causes of recurrent fever (cycle of fever and afebrile) days? weeks?
malaria, meningiococemia, cholangitis, dengue f., yellow f., Colorado tick f., relapsing f. (borrelia) and influenza; Hodgkins disease (pel-ebstein fever), brucellosis, relapsing F. (Borrelia), ocassionally TB
What are some general features of drug fever?
common cause, only sign of drug rxn in 3-5%, increased risk w/ more drugs taken (esp. elderly), increased risk w/ HIV
What are the mechanisms of drug fever?
hypersensitivity, altered thermoregulatory mechanisms, directly related to administration, related to pharmacologic effect, idiosyncratic reactions
What are the features of drug fever due to hypersensitivity?
most common, Ag-Ab complex formation, T-cell response, usually in 3 days, but up to years, may see: rash, uticaria, mucosal ulcers, liver, kidney, lung, bone marrow dysfunction
What are the features of drug fever due to altered thermoregulation?
exogenous thyroid hormone (inc. metabolic rate-> inc heat production), anticholinergics (dec. sweating-> dec. heat loss), and sympathomimetics (inc. vasoconstriction-> dec. heat loss; amphetamine and cocaine)
What are the features of drug fever due to drug administration?
IV fluid contaminated with endotoxin, chemical phlebitis, local inflammation at injection site, low-grade fever after vaccines, intrinsic pyrogenic prop. (amphotericin B, bleomycin)
What are the features of drug fever due to pharmacologic effect?
chemotherapy (dying cells pyrogens-> cytokine release; Jarish-Herxheimer rxn (Antibiotic rxn-> dead bugs-> induce cytokines), may see rash, symptoms worse (syphilis, brucellosis, enteric fever)
What are the idiosyncratic rxns that cause drug fever?
malignant hyperthermia, neuroleptic malignant syndrome (NMS), serotonin syndrome, glucose-6-phosphate dehydrogenase deficiency
What are the features of malignant hyperthermia?
(rare), T >40C, muscle rigidity, metabolic acidosis, and BP instability, occurs during anesthesia (halothalene, succinylcholine), autosomal dominant in 50%, mutation in ryanodine receptor (Ca channel in skeletal muscle SR)
What are the features of NMS?
high fever, muscle rigidity, altered mental state and dysautonomia (BP up and down), >25 drugs (all deplete CNS dopamine), major tranqs (haloperidol), significant mortality, RX: DC drug, dantrolene, bromocriptine
what are the features of serotonin syndrome?
agitation, hyperthermia, diaphoresis, tachycardia, rigidity (similar to NMS), inc. stimulation of 5HT1A receptors (SSRI meds, inc. risk if given with linezolid), also LSD, lithium, L-dopa, and MAO-inhibitors
What are the features of drug fever with G-6-PD deficiency?
fever with: primaquine, quinine sulfate and sulfonamides, hemolytic anemia is more worrisome
What is fever of unknown origin? setting?
> 38C (101F) every day or repeatedly, 3wk duration (eliminates self-limited cause), no Dx after > 2 visits or 3d in hospital; community, clinic, or hospital
What are the leading causes of fever of unknown origin?
infection (30-40%), Neoplasm (20-30%), collagen or vascular (10-15%), granulomatous (5-10%), Misc (10-20%), and unknown (10-15%)- SQ fecal injection to induce, etc
What infections are a leading cause of FUO?
occult abscesses, TB, endocarditis, CMV
What neoplasms are a leading cause of FUO?
leukemia, lymphoma, myeloma, hyerpnephroma, and hepatoma
What collagen or vascular conditions are a leading cause of FUO?
SLE, RA, rheumatic fever, arteritis
What granulomatous diseases are a leading cause of FUO?
sarcoidosis, granulomatous hepatitis, IBD
What are the miscellaneous leading causes of FUO?
drug, PE, thermoregulatory disorder, endocrine disorder (hyperthyroid, Addison’s, pheochromocytoma), factitious/fraudulent
What are the common causes of nosocomial FUO?
hospital acquired infections, post-op complications, and drug fever
What are the common causes of FUO in cancer or transplant patient?
majority infection!, cause documented in only 50%
What are the common causes of FUO in HIV or AIDS patient?
HIV primary infection, mycobacterial (TB or NTM esp MAI), CMV- toxoplasmosis, lymphoma
