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The study of disease, a discipline bridging clinical practice and basic science
Refer to the cause of disease
The mechanism of development of disease
Identify changes in the gross or microsocpic appearance
What is another term for oxygen deficiency?
Blood supply deficiency
What are the causes of cell injury?
- 1. Hypoxia - oxygen deficient
- 2. Physical Agent (i.e. trauma, radiation)
- 3. Chemical and Drugs (i.e. chemical can cause pH imbalance, Drugs can damage liver)
- 4. Microbiological Agents (i.e. bacteria, virus', parasites, etc)
- 5. Other (i.e. genetics, malnutrition, immune response)
What is a form of Reversible Cell Injury?
Cellular Swelling / Fluid Retention (Hydropic Change)
Cell nuclei become darker and smaller
This is a form of Irreversible Cell Injury
Cell nuclei "ruptures"
This is a form of Irreversible Cell Injury
Total nucleic breakdown
This is a form of Irreversible Cell Injury
What are forms for Irreversible Cellular Injury?
Shrinkage in size of cell by loss of cell substance
What are some causes of atrophy?
- Reduced Functional Demand (i.e. Stroke)
- Insufficient Nutrients
- Inadequate Supply of Oxygen
- Persistent Cell Injury
Increase in the size of a cell accompanied by an augmented functional capacity
What are some causes of Hypertrophy?
- Physiologic - Pregnancy and the stretching of the uterus
- Pathologic - Congestive Heart Failure
Increase in the number of cells in an organ or tissue
What are some causes of Hyperplasia?
- Physiologic - hormonal stimulation (i.e. breast growth in puberty)
- Pathologic - endometriosis
One adult cell type is replaced by another. May be a precancerous lesion.
What are some causes of Metaplasia?
Lung epithelial cells have changed to squamous cells through many years of smoking
Is the reaction of the microcirculation to any injury characterized by movement of fluid and leukocytes from the blood into extravascular tissues
What are some forms of inflammation?
- Active Hyperemia - Increased blood supply in the effected area
- Cellular Exudation - WBC's exit to tissue (site of inflammation)
What is the difference between Edema and Effusion?
- Edema - fluid in tissues
- Effusion - fluid in cavities
- These are both forms of Inflammatory Edema
A form of Inflammatory Edema in the Effusion category.
Fluid is clear due to low cell count and low protein content
A form of Inflammotory Edema in the Effusion category.
Fluid is cloudy / turbid due to high cell count and high protein content
A form of Inflammatory Edema in the Effusion category.
Fluid containing Red Blood Cells (RBC) is found in the cavity.
The adhesion of white blood cells (WBC) to the epithelial cells of blood vessels that occurs at the site of an injury during the early phases of
Margination and Adherence (two forms of cellular recruitment)
WBC move from intravascular to extravascular at the site of inflammation where "battle" ensues. At the this point WBC's can perform one of two processes 1. engulf pathogen 2. release chemical that attracts more WBC's to the scene.
The process of cellular devouring.
These cells identify the pathogen, then engulf's the pathogen
What are some systematic manifestations of inflammation?
- 1. Fever
- 2. Leukocytosis (excess of WBC, typically found in bacterial infections)
- 3. Leukopenia (defeciency of WBC, typically found in viral infection)
Cells that multiply constantly throughout life due to the lack of G0 Phase (Cell cycle) (i.e. skin cells, cells in the Gastrointestinal Tract (GI Tract), blood cells in the bone marrows)
Labile Cells (Unstable Cells)
Cells that remain primarily in the G0 phase of the Cell Cycle. They are normally renewed very slowly but are capable of more rapid renewal after tissue loss (i.e. endocrine, liver, proximal renal tubules)
Cells that do not have the ability to multiply. If lost then there is no replacement of its same kind. Scar tissue replaces theses kinds of cells (i.e. brain cells / neurons, heart muscles cells)
What is the process of Wound Healing?
- 1. Wound Contraction
- 2. Repair
- 3. Regeneration
A form of "Fibrin Plug" Formation
Process of blood vessel production.
Cell growth in the affected area
Cells other than the original that are replaced due to injury of the original cells present. These new cells have no function.
Scar Tissue / Scar Formation
The renewal of the lost tissues or part in which the missing cells are replaced by identical ones.
Healing of wounds with Apposed Edges (edges of wound are close to each other); minor tissue loss, no scar tissue formation, typically found in patient that have undergone surgery.
Healing of wounds with Separated Edges; tissue loss can occur and may be contaminated with bacteria, typically found in patients who have experienced trauma.
Which type of hypersensitivity is involved with allergic reactions? Which type of antibody is associated with this types? What types of cells do these antibodies attach to?
Which type of hypersensitivity is involved with extensive cross linking? Which type of antibody(s) is associated with this types?
Diseases of this type include - Rheumatiod arthritis, Systemic Lupus Erythematosus, serum sickness, glomerulo-nephritis
The cross linking / complexes refers to the antibody-antigen-anitbody chains that form. A build up of these can cause an inflammatory response
Which cells are affected by HIV?
- CD4 / Thelper Lymphocytes
- Since CD4's are involved in all aspects of immunity (assits B cells, NK cells, monocytes) the virus greatly impairs immune function
- Infected patients can be asymptomatic for up to 10 years while their CD4 count continues to drop. As the CD4 count reaches levels below 200 cells per Liter symptoms start to appear.
- If the ratio of CD4:CD8 is less than 1:1, the diseases progresses rapidly
What is Persistent Generalized Lymphadenopathy?
Infection of lymph nodes after 3+ months of HIV infection
AIDS patients don't die from the virus but due to opportunistic infections. Give some examples.
- Jirovecii - a form of Pneumonia
- Cryptococcal Meningitis
- Staphylococcus aureus
- Kaposi Sarcoma - AIDS associated Cancer attack GI Tract or Lungs
Any new and abnormal growth, specifically a new growth of tissue in which the growth is uncontrolled and progressive.
A new growth of tissue
A neoplastic disease that which is fatal. Exhibits invasiveness and metastasis.
A malignant growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastasis.
Any group of tumors usually arising from connective tissue
Tumors that do not penetrate (invade) adjacent tissue borders, nor do they spread (metastasize) to different sites
Tumors that invade tissues and metastasize to distant sites. From these distant sites they metastasize and further invade.
What is the tumor marker that is tested in cases of Liver cancer?
αFP - alpha-fetoprotein
What is the tumor marker that is tested in cases of cancers of the pancreas, liver, colon and kidney?
- CEA - carcinoembryonic antigen
- Clinically speaking, it tests for colo-rectal cancers
- This test is not good for early stages of these types of cancers but can be used in a monitoring capacity
What is the tumor marker that is tested in cases of cancers of the prostate?
PSA - prostate-specific antigen
What is the tumor marker that is tested in cases of cancers of the pancreas?
- CA 19-9
- This test gives more details for pancreas than CEA
What is the tumor marker that is tested in cases of ovarian cancer?
A condition where plaque builds up in medium-sized and large arteries. The plaque contains lipids, inflammatory cells, smooth muscles cells, and connective tissue.
- Plaque comes in 2 form - stable and unstable
- Stable - form slowly over several decades
- Unstable - vuneralbe to spontaneous rupture
What are some risk factors associated with atherosclerosis?
- Dyslipidemia - High LDL or Low HDL
- C-reactive protein (CRP) - cannot detect severity but predicts likelihood of ischemic events
Impairment of blood flow through the coronary arteries, most commonly by atheromas.
- Coronary Artery Disease (CAD)
A temporary sudden narrowing of one of the coronary arteries (the arteries that supply blood to the heart). It slows or stops blood flow through the artery and starves part of the heart of oxygen-rich blood.
Chest pain due to ischemia (a lack of blood, thus a lack of oxygen supply and waste removal) of the heart muscle, generally due to obstruction or spasm of the coronary arteries (the heart's blood vessels)
Angina Pectoris - usually aggrevated upon exertion (i.e. strong emotions, after a meal, cold weather)
This condition is a result of acute obstruction of coronary artery.
ACS - Acute Coronary Syndrome (i.e. unstable angina, STEMI, NSTEMI)
Cardiac markers are released in the bloodstream after myocardial cell necrosis (heart muscle cell death) that can be tested for, what are these markers?
- Creatinine kinase (CK-MB) - cardiac enzyme
- Troponin I & T - cell contents
What is the range of systolic BP and / or diastolic BP to constitute hypertension?
Accounting for 90–95% of all cases of hypertension
Environmental factors include dietry Salts, obesity, stress, sendentary lifestyle, tobacco, alcohol, long use of birth-control
- Primary Hypertension
- Increased Na making cells more sensitive to sympathetic stimulation (Sympathetic NS increases BP)
- Severe hypertension leads to damage to cardiovascular system, brain, and kidneys
- Increased risk of CAD, MI, stroke, renal failure
- History of other symptoms (CAD, HF, stroke, renal dysfunction, peripheral arterial disease, dyslipidemia, diabetes, gout)
- 4th heart sound (a 3rd heart sound can be heard in young adults / teenagers)
- Retinal changes (i.e. narrowing, hemorrhages, exudates, arteriole constriction / sclerosis / hemorrhages / exudates, papilledema
- Multiple measurements of BP
- Urinalysis of creatinine ratio
- Blood tests for fasting lipids, creatinine, K
- Aldosterone if K is low
- LV hypertrophy
- Sometimes TSH (thyroid-stimulating hormone)
Accounting for 5% of all cases of hypertension
Due to chronic kidney disease
Most Congestive Heart Failure (CHF) is due to impairment of what?
- LV Failure due to CAD / hypertension (cough and asthma occurs in this case)
- RV Failure due to a prior LV failure (congestion occurs in this case)
A state in which blood flow to the perfusion of peripheral tissues are inadequate to sustain life because of insufficient cardiac output or maldistribution of peripheral blood flow, usually associated with hypotension and oliguria (no / low urine production)
- Hand and Feet are cold, moist, cyanotic (blue / purple) and pale
- Tachypnea (rapid breathing)
- Systolic BP < 90 mm HG / unobtainable
- Urine flow < 30 mL/h
Name the 3 types of shock and their differences.
- Hypovolemic Shock - low volume of intravascular blood
- Vasodilatory Shock - low volume of intravascular blood due to vasodilation
- Cardiogenic Shock - low output of blood due to low intravascular volume
An acute infection of lung parenchyma (functional parts of an organ) including alveolar spaces and interstitial tissue
- Symptoms: cough, fever, sputum production, exudates, shortness of breath, sometimes chest pain
- These signs / symptoms can lead to progressive pneumonia, pericarditis, septic arthritis, endocarditis, meningitis (bacterial)
What is the most common bacteria that causes pneumonia in adults over 30?
Streptococcus pneumoniae (gram-positive, accounts of 2/3 of bateremic pneumonias, most common in patients of extreme age / winter-time)
Major pulmonary pathogens in infants / children are due to viruses
A pulmonary disease characterized by reversible airway obstruction, airway inflammation, and increased airway responsiveness to a variety of stimuli
- Asthma - due to spasm of airway smooth muscle, edema of airway mucosa, increased mucus secretion, infiltration of airway walls, desquamation of the airway epithelium
- Symptoms: wheezing, coughing, shortness of breath, tachypnea, tachycardia
What are some examples of Chronic Obstructive Pulmonary Disease (COPD)?
- Chronic Bronchitis - 3+ months in each of 2 successive years
- Emphysema - enlargement of airspaces with destruction of their walls
- Airflow Obstruction
- Risk Factors:
- Air pollution
- Hyperresponsive airways (allergic)
- α-1-antitrypsin deficiency (enzyme inhibitor of elastase; can be found on chromosome 14)
What are signs / symptoms of emphysema?
- α-1-antitrypsin deficiency
- cough, purulent sputum, wheezing, dyspnea, hemoptysis, cyanosis
- hypoxemia (possibly leading to respiratory acidosis)
- hypercapnia (high CO2 in the blood)
- "barrel-chest" (increase in diameter of chest)
Tumors of this region may be primarily metastatic from other sites in the body. They are typically malignant.
These cancer cells deprive healthy tissue of oxygen and nutrients.
- Tumors of the Lung
- Bronchogenic Carcinoma (95% of lung cancer cases) - arise from epithelial or lining cells of bronchi / bronchioles
- Mesothelioma - cancers that arise from the pleura
Bronchogenic carcinomas has two basic types. Name them and their differences.
- Small Cell Carcinoma (SCC) (20% of all cases): distinctive small round-to-oval cells that resemble lymphocytes, grows much more rapidly then NSCC
- Non-Small Cell Carcinoma (NSCC): adenocarcinoma (35%), squamous cell carcinoma (30%), large cell carcinoma (10%) -- early detection and treatment leads to better prognosis
Globally, lung cancer is the most frequent type of cancer in which patients?
In the United States, which cancer is currently the second most common cancer diagnosed in both genders?
- Lung Cancer: in both genders (Prostates cancer comes 1st in males and Breast cancer comes 1st in females)
- African-Americans and Caucasian males carry the greatest risk for developing lung cancer
- Lung cancer is extremely difficult to detect in early stages
- 1-year survival rate - up to 42%
- 5-year survival rate - up to 15%
- Intrathoracic: cough (60% of patients), hemoptysis (coughing up blood - very bad sign), chest pain
- Extrathoracic: anorexia, unintended weight loss, lack of energy
- Risk Factors:
- Smoking (including second-hand)
- Exposure to asbestos
- Radon gas
- Genetic factors
- Air pollution
Decrease in the number of RBC's and Hb (hemoglobin) content caused by blood loss, deficient erythropoiesis (RBC production), excessive hemolysis (RBC destruction), or any combination of the above.
- Men - RBC < 4.5 million/μL; Hb < 14 g/dL; Hct < 42%
- Women - RBC < 4 million/μL; Hb < 12 g/dL; Hct <37%
What are the signs / symptoms of Acute Posthemorrhagic Anemia (Anemia caused by Blood Loss)?
- Weak and rapid pulse
- Rapid respiration
- *This anemia is normacytic in nature (normal-sized cells)
Deficient or defective heme or globin synthesis produces which type of anemia?
- Iron (Fe) Deficient Anemia (Microcytic type (small-cell RBC population))
- Total normal body Fe: Men - 3.5g; Women - 2.5g
- Signs / Symptoms: pica (ingesting non-foods (dirt, paint)), pagophagia (craving for ice), glossitis (tongue inflammation)
- Diagnosis criteria: absent marrow stores of Fe
- *Ascorbic Acid helps with Fe absorption
B12 deficiency caused by loss of intrinsic factor secretion
- Pernicious Anemia (Anemia caused by Vitamin B12 Deficiency; Macrocyctic type)
- Normally B12 is complexed with intrinsic factors and absorbed through the ileum
- Signs / Symptoms: splenomegaly, hepatomegaly, GI manifestations, Glossitis, neurologic involvement
- Diagnostic findings: achlorhydria (decreased acid production in stomach
This anemia is similar in manifestations to Pernicious Anemia. What is it? How are the two diagnostically different?
- Folate Deficient Anemia
- B12 has neurologic signs, B9 does not
This type of anemia has a shortened RBC life span (normal is ~120 days). The bone marrow production can no longer compensate for the shortened RBC survival.
- Anemia Caused by Excessive Hemolysis
- Signs / Symptoms: Hemolysis and Erythoropoiesis (due to reticulocytosis (hyperactive bone marrow))
Chronic hemolytic anemia occuring almost exlusively in blacks and characterized by malformed RBC's caused by homozygous inheritance of Hb S (due to amino acid "mistake")
- Sickle Cell Anemia
- The malformed shape caused obstruction in vessels and may cause tissue death due to hypoxia; destruction occurs soon after entering circulation
The most common inherited hemolytic disorder. It results from unbalanced Hb synthesis caused by decreased production of at least one globin polypeptide chain.
Thalassemia (common in Mediterranean, African, SE Asian ancestry)
This cancer takes up space in the bone marrow making "normal" cell production lower.
Leukemia - due to 1. Epstein-Barr Virus 2. T-cell leukemia / lymphoma virus
What is the most common malignancy in children ages 3-5 yrs?
ALL - Acute Lymphoblastic Leukemia
Abnormal, excessive generation of thrombin and fibrin in the circulating blood
- DIC - Disseminated Intravascular Coagulation
- Too slow - excessive clotting may lead to vein thrombosis (DVT)
- Too fast - bleeding
What is the difference between aPTT and PT?
- Shared - Factors I, II, V, X
- aPTT - Factors VII, IX, XI, XII
- PT- Factor VII
This portion of the brain modulates the activities of the anterior and posterior lobes of the pituitary.
This hormone stimulates synthesis and secretion of both throid-stimulating hormone and prolactin.
Thyrotropoin-releasing hormone (TRH)
This hormone stimulate the release of ACTH from the pituitary. The ACTH stimulates the adrenal cortex to secrete cortisol and androgens.
Corticotropin-releasing hormone (CRH)
This hormone regulates the structure and function of the thyroid gland and stimulates synthesis and release of thyroid hormones. The synthesis and secretion of this hormone are controlled by stimulatory action of the hypothalamic hormone TRH and by suppressing negative feedback action of circulating thryoid hormone from the periphery.
Thyroid-stimulating hormone (TSH)
The portion of the brain secretes antidiuretic hormone (ADH, vasopressin) and oxytocin.
The major action of this hormone is to promote water conservation by the kidney. At high concentration it also causes vasoconstriction.
Antidiuretic horome (ADH)
A clinical condition encompassing several specific diseases, characterized by hypermetabolism and elevated blood serum levels of free thyroid hormones (T3, T4).
- Hyperthyroidism - may be result of increased synthesis and secretion of thyroid hormones (T3, T4) from the thyroid gland, caused by thyroid gland stimulators in the blood or autonomous thyroid hyperfunction.
- Characterized by goiter, exophthalmos (bulging of eye), pretibial myxedema
- Ingestion of excess quantities of thyroid hormones can also lead to this.
- Excess Iodine ingestion can also cause this.
- Thyroiditis may also cause this.
- *All patients with hyperthyroidism have essentially undetectable serum TSH levels.
- Widened pulse pressure (the difference between systole and diastole; i.e. 120/70 = 50; 130/60 = 70)
- Warm, fine, moist skin, tremors, eye signs, nervousness / shaking, increased activity
This condition is the most common cause of hyperthyroidism.
Grave's Disease - an antibody against thyroid TSH receptor, which results in continuous stimulation of the gland to synthesis and secrete excess quantities of T3 and T4.
Thyroid hormone deficiency
The most common form is probably an autoimmune disease
- Hypothyroidism (myxedema)
- Low count of T4 and T3 affects cell metabolism
- The second most common form is posttherapeutic hypthyroidism
- Dull facial expression
- Speech is slow
- Facial puffiness
- Cold intolerance
- Coarse, dry, scally, thick skin
- Intellectual impairment
An insidious, usually progressive disease resulting from adrenocortical hypfunction.
70% of cases are due to idiopathic atrophy of the adrenal cortex, probably caused by autoimmune processes.
Could also be caused by destruction of adrenal gland by granuloma (i.e. TB)
There is an increased excretion of Na and decreased excretion of K, chiefly in the urine
- Addison's Disease
- Signs / Symptoms: weakness, fatigue, hypotension
Clinical abnormalities due to chronic exposure to excesses of cortisol.
Hyperfunction of adrenal cortex may be ACTH-dependent.
May be independent of ACTH regulation (i.e. production of cortisol by an adrenocortical adenoma or carcinoma)
- Cushing's Syndrome
- Sign / Symptoms: rounded "moon" facies, truncal obesity, distal extremities and fingers are usually reduced resistance to infection, increased glucose tolerance
Impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia, polyphagia, and ployuria. Later complications include vascular disease, peripheral neruopathy, and predisposition to infection. Diagnosis is by measuring plasma glucose.
- Diabetes Mellitus (DM)
- Symptoms: Hyperglycemia, Polyuria, Polydipsia, Polyphagia, Hypotension, Dehydration (severe enough can cause weakness, fatigue)
- Type 1 present symptomatic hyperglycemia and sometimes ketoacidosis (DKA)
- Type 2 may present symptomatic hyperglycemia but are often asymptomatic
- Microvascular complications (affecting small vessels)
- Macrovascular complications (affecting large vessels)
- *Patients with poorly controlled DM are prone to bacterial and fungal infections
- *Foot complications (skin changes, ulceration, infection, gangrene)
- FPG - fasting plasma glucose (8-12 hour fast and then take blood
- OGTT - Oral Glucose Tolerance Test (2 hours after ingesting concentrated glucose solution)
- Measure HbA1c (A1c > 6.5%) - reflects the previous 2-3 months glucose levels
Insulin production is absent because of autoimmune pancreatic β-cell destruction.
Type 1 DM - this type accounts for < 10% of all DM cases
Over 90% of patients with Type 1 DM have this present.
HLA - Human Leukocyte Antigen
Insulin secretion is inadequate. Often insulin levels are very high, especially early in the disease.
Hyperglycemia develops when insulin secretion can no longer compensate for insulin resistance.
Obesity and weight gain are important determinant of insulin resistance
- Type 2 DM
- Risk Factors:
- Age > 45 years
- Sedentary Lifestyle
- Family History of DM
- History of impaired glucose regulation
- Gestational DM / delivered baby > 4.1 kg (~9 lbs)
- History of hypertension / dyslipidemia
What are the 3 most common manifestations of Microvascular DM?
- Retinopathy - most common cause of adult blindness in US
- Nephropathy - leading cause of chronic renal failure in the US
- Neuropathy - resulting from nerve ischemia
What are some manifestations of Macrovascular DM?
- Angina pectoris and MI
- Transient ischemic attacks and strokes
- Peripheral arterial disease
An acute complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis.
Diabetic Ketoacidosis (DKA)
Glucose intolerance that appears for the first time during pregnancy
Gestational Diabetes (GDM)
What is the term for Vomiting of Blood?
What is the term for Passage of Gross Blood through the rectum?
What is the term for Passage of Black Tarry Stool?
Melena (100-200 mL of Blood in the Upper GI can produce this case)
This particular GI issue is usually tested for and not easily visible.
- Occult chronic bleeding from the GI Tract
- *Tests include: Dectection of Blood in Feces (typically patients >= 60 yrs); Iron Deficiency is also an indication (in cases of sufficent bleeding)
Where is the source of bleeding in cases of GI bleeding?
- Upper GI Sources: esophagus, stomach, mouth
- Lower GI Sources: SI, LI, Rectum
- Sign / Symptoms: Shock, Anemia, change if pulse / BP
The GI mucosa is protected by several distinct mechanisms. What are they?
- 1. Mechanical production of mucus and HCO3- (barrier against acid)
- 2. Epithelial cells remove excess hydrogen ions
- 3. Mucosal blood flow removes excess acid
This form of gastritis can be caused by drugs (i.e. NSAID's, aspirin), alcohol, stress.
- Acute Gastritis
- *the stress is acute
- Risk Factors:
- Severe Burns
- CNS Trauma
- Sepsis (whole-body inflammatory state, "blood poisoning")
This form of gastritis can be caused by H. pylori leading gastric ulcersw and gastric adenocarcinoma.
- Chronic Gastritis (primary cause of gastritis, highest concentration found in antrum (stomach)
- *very common chronic infection worldwide; most frequently aquired in childhood
- Found in conditions which are unsanitary (oral-oral / fecal-oral transmission)
What test can you perform to check of H. pylori?
Rapid Urease Test (RUT) - gastric biopsy specimen is dropped in solution, if solution changes color then positive for H. pylori, 90% accurate)
What are the causes of Peptic Ulcer Disease (PUD), in order?
- 1. H. pylori
- 2. Acid hypersecretion
- 3. NSAID's (i.e. aspirin)
- Two Kinds of Ulceration: Gastric, Duodenal
What is the mechanism by which H. pylori casues mucosal injury, in order?
- 1. Ammonia
- 2. Cytotoxins
- 3. Mucolytic enzymes
- 4. Cytokines
What are the Signs / Symptoms of PUD?
- Epigastric pain - relieved by food / antacids
- Burning sensation
- Chronic and Recurrent
- Gastric Ulcers - Pain after eating (~30 mins after)
- Duodenal Ulcers - Pain after eating (~2-3 hours after)
What is happening, physiologically, in the cases of Acute Pancreatitis?
- Due to the obstruction of this site, the juices have no where to go and the pancreas swells (inflammation)
- Can be due to Biliary Tract disease, alcoholism (>= 80% of hospital admissions), drugs, pancreatic enzymes eating away at organ
- Elevated WBC count
- Severe Abdominal Pain, which radiates through back
- Laboratory testing of Serum amylase (carbs) and lipase (fats) concentrations can give impression on severity of condition
Inflammation of the lining of the stomach and intestines, predominantly manifested by upper GI tract symptoms (anorexia, nausea, vomiting), diarrhea, and abdominal discomfort.
- Gastroenteritis - can be due to bacterial, viral, parasitic
- Can be due to person to person contact (E. coli, Salmonella, Norwalk virus)
- Signs / Symptoms - sudden onset and sometimes dramatic, anorexia, nausea, vomiting, borborygmi, abdominal cramps, diarrhea (with or without blood and mucus)
This virus can cause infections year round. 40% of outbreaks of gastroenteritis is in children and adults.
This virus causes approximately 90% of epidemic nonbacterial outbreaks of gastroenteritis around the world.
This virus typically occurs during the winter month (Nov / Dec). Severe cases are hospitalized with serious diarrhea, usually in children under 2 years. This virus causes dehydrating diarrhea in young children (3-15 months). Most infectious in the late fall and winter months.
What are the major causes of gastroenteritis, in order?
- 1. Enterotoxins - impair intestinal absorption and can provoke secretion of electrolytes and water
- 2. Penetration of mucosa (due to Shigella, Salmonella, E. coli species)
- 3. Chemical toxins (i.e. poisonous mushrooms, potatoes, seafood)
- 4. Heavy metals (i.e. arsenic, lead, mercury (Hg), cadmium)
- 5. Drugs (i.e. broad spectrum antibiotics altering normal gut flora)
This bacteria can occur when one ingests undercooked beef or unpasteurized milk. Can be transmitted fecal-orally.
Escherichia Coli (E. coli O157:H7)Signs / Symptoms - severe abdominal cramps and watery diarrhea that may become grossly bloody within 24 hours.
This condition is caused by staphylococcal enterotoxin, not by staphylococcus itself. Food handlers with skin infections contaminate food left at room temperature.
- Staphylococcal Food Poisoning
- Sign / Symptoms - severe nausea and vomiting (2-8 hours after eating food containing toxins; attack is brief, often lasting 12 hours)
Acute inflammation of colon caused by C. difficile and antibiotic abuse.
- Antibiotic-Associated Colitis - an alteration of normal colonic flora that allows overgrowth of C. difficile
- *almost any antibiotic can lead to C. difficlie
Fake membrane consisting of fibrin, WBCs and necrotic epithelial cells
This inflammatory bowel disease primarily affects the small intestines but may be found in other parts of the GI tract.
Crohn's Disease / Regional Enteritis
What are the causes of Crohn's Disease, in order?
- 1. Genetic
- 2. Immune response (due to environmental, dietary, or infectious agents)
- 3. Smoking*seen in Nothern Europeans, Angelo-Saxons; most common among Jews
An abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect.
A pattern of inflammation in a "tubular" organ like colon or vessels which involves the whole thickness of the tubule wall (obstruction).
Obstruction of small intestines which are in segments ("skip areas")
- Segments of diseased
- 35% Ileitis
- 45% Ileocolitis
- 10% Jejunoileitis
- Signs / Symptoms: Chronic Lower GI issues, chronic diarrhea, abdominal pain
- *If colon alone is affected, it is clinically indistinguishable from that of ulcerative colitis.
A motility disorder involving the entire GI tract, causing recurring upper and lower GI symptoms, including variable degrees of abdominal pain, constipation and / or diarrhea, and abdominal bloating.
- Irritable Bowel Syndrome (IBS): No pathologic cause can be found. Caused by emotional / stress, diet (high protein, low fiber), drugs, hormones affect GI motility.
- *It is believed that the circular and longitudinal muscles of the small bowel and sigmoid are particularly susceptible to motor abnormalities, but this is only a hypothesis.
- Pain relieved by defecation
- Alternating pattern of constipation and diarrhea
- Abdominal distention
- Mucus in stool
- Sensation of incomplete evacuation after defecation
- *There are two major IBS types - constipation predominant IBS and diarrhea predominant IBS
- The Rome Criteria: abdominal pain relieved with defecation and a varying pattern of altered stool frequency of form, bloating, or mucus
- *Any pathologic disorders should be ruled out
Incompetence of the lower esophageal sphincter allows reflux of gastric contents into the esophagus, causing burning pain. Prolonged refulx may lead to chronic esophagitis, and in worst cases, cancer.
Gastroesophageal Refulx Disease (GERD)
The most common malignant tumor in the proximal two-thirds of the esophagus
- Squamous Cell Carcinoma (common in parts of Asia & S. Africa)
- 4-5 times more common in blacks than whites
- Risk factors include alcohol ingestion, smoking, achalasia (incompetent sphincter muscles), human papillomavirus (HPV)
The most common malignant tumor in the distal one-third of the esophagus
- 4 times more common among whites than blacks
- Risk factors include smoking
What are the signs and symptoms of Esophageal Cancer?
- Early stage: asymptomatic
- Dysphagia (trouble swallowing) - progressivly degrades to the point that swallowing saliva is difficult
- Poor Prognosis (5 yr survival < 5%)
This plays a significant role in causing stomach cancer.
- Helicobacter pylori (H. pylori)
- Gastric adenocarcinoma accounts for 95% of malignant tumors of the stomach
What are signs and symptoms of Stomach Cancer?
- Satiety (always feeling full), Obstruction, Bleeding (late stage)
- Diagnosed through endoscopy, then CT11,000 deaths (low) in U.S. annually (7th most common cause of death from cancer)
- Extremly high in Japan and China75% of patients, age > 50 yrs
- Blood tests including CBC should be done to assess anemia
- CEA should be measured before and after surgery
What are the common causes of Stomach Cancer?
- 1. H. pylori
- 2. Autoimmune atrophic gastritis and various genetic factors
- 3. Gastric polyps - precursors to cancer
- 4. Chronic gastritis leading to ulcers
An extremely common form of cancer. Symptoms include blood in stool or change in bowel habits
Screenings for fecal occult blood (FOB) are done (annually after age 50 yrs).
Diagnosis through colonoscopy (instead of sigmoidoscop)
- Colorectal Cancer
- 153,000 cases and 52,000 deaths annually
- New cases on the rise but still not beating Lung Cancer rise
- Age > 40 yr rising and tapering off age 60-70 yrs
- 70% of cases occur in the rectum and sigmoid
- 95% adenocarcinomas
What is the etiology of Colorectal Cancer?
- 1. Transformation of Adenomatous polyps
- 2. Chronic Ulcerative Colitis
- 3. Diet (High Protein / Fat / Refined Carbs, Low Fiber).
- Signs / Symptoms: occult (hidden) bleeding, fatigue and weakness due to severe anemia, alternating constipation and increased stool frequency or diarrhea
The largest and most metabolically complex organ.Has a remarkable capacity for regeneration in response to injury of this organ.
The liver consists of many microscopic functional units
These make up the bulk of the liver
Hepatocytes (parenchymal (functional part) cells)
What are the important function of hepatocytes?
- 1. Regulation of carbohydrate homeostasis
- 2. Excretion of Bile
- 3. Clotting factors
- 4. Serum Albumin
- 5. Formation of Urea
- 6. Detoxification of Drugs
Increased bilirubin production
Decreased liver uptake / conjugation
Decreased biliary excretion
Are found in what condtion?
What compounds are tested for in cases of liver conditions?
- ALP (alkaline phasphatase - found in liver, bone, placenta): this compound is detected when there is an impairment of bile formation
- GGT (gamma-glutamyl transpeptidase): the compound is detected when there is an obstruction of the common ducts
- AST (aspartate transaminase): indicates liver injury (rises in cases of MI, heart failure, muscle injury, CNS disease)
- ALT (alanine aminotransferase): found in liver cells indicating liver disease
- Serum Albumin: decreased in chronic liver disease
- Serum Ig: rises in cases of chronic liver disease
- αFP (alpha fetoprotein): increase indicates primary hepatcellular carcinoma
Excessive accumulation of lipid in hepatocytes. The most common response of the liver to injury. The most common cause of macrovascular type of this condition
- Fatty Liver
- Pathogenesis: triglycerides accumulate in the liver because of increased input through synthesis from FFA (free fatty acids) or decreased export as VLDL from the hepatocytes. Increased triglyceride synthesis may result from increased delivery or availability of FFA or from decreased oxidation of FFA in the liver
- Due to:
- 1. Alcoholism
- 2. Obesity
- 3. Diabetes
- Pathology: Triglycerides accumulate as large droplets displacing nuclei making cells look "fat"
A spectrum of clinical syndromes and pathologic changes in the liver caused by alcohol (ethanol). This condition is #1 associated with Fatty Liver Disease.
- Alcoholic Liver Disease
- Pathogenesis: major factor is the quantity of alcohol consumed, patients nutritional status, genetic, and metabolic traits
- If consumed in large quantities & regularly for years will produce liver injury; Women - 20g, Men- 60g
- Greater susceptibility in females
- Over 90% of Alcohol is metabolized by the liver
- Alcohol eventually metabolizes into Acetaldehyde (which can cause lipid metabolism problem)
- Pathology: simple accumulation of neutral fat in hepatocytes to cirrhosis and hepatocellular carcinoma
- Sign / Symptoms: Patient with a fatty liver are usually asymptomatic
- Tests show an increase in GGT (detects obstruction of common duct)
- AST & ALT are elevated too, but AST > ALT in elevation
Diffuse disorganization of normal hepatic structure by regenerative nodules that are surrounded by fibrotic tissue.
- Cirrhosis: due to chronic alcohol abuse (Asia & Africa get cirrhosis due to HBV leading to death)
- 1. Involve entire liver
- 2. Fibrosis (irreversible), even with regenerating nodules
- 3. Usually irreversible damage
- Pathogenesis: Cirrhosis is end stage of many forms of liver injury, fibrosis & regenerating nodules (no chance of recovery)
- "Bridges" connect hepatic artery and portal vein to hepatic venules, restoring intrahepatic circulation; increased portal vein pressure leads to portal hypertension
- Signs / Symptoms: portal hypertension with variceal bleeding, ascites, or liver failure;
- Many patients with cirrhosis are typically asymptomatic
- Other: weakness, anorexia, malaise, weight loss
- Dramatic presentation: massive GI bleeding from esophageal varices (second to portal hypertension)
- Firm liver with blunt edge is typical, splenomegaly, palmar erythma (due to vasodilation of skin), testicular atrophy
- Complications: Splenomegaly, jaundice, ascites, hepatocellular carcinoma
- Decreased Serum Albumin and prolonged PT (clotting), modest elevation of ALT, hypersplenism also can lead to leukopenia and thrombocytopenia
- Ultrasound may reveal textual abnormalities
An inflammation of the liver characterized by diffuse or patchy necrosis affecting all acini (berry-shaped cell clusters)
- Hepatitis: major causes hepatic viruses, alcohol, and drugs
- Pathology: hepatocellular necrosis, mononuclear inflammatory infiltrate
- Signs / Symptoms:
- 1. Nausea & vomiting / anorexia
- 2. Fever
- 3. Jaundice
- Lab finding: Increased levels of Bilirubin, ALT, AST
- Prognosis: Usually resolves 4-6 weeks (acute state)
Diffuse liver inflammation caused by specific hepatotropic viruses
- Acute Viral Hepatitis
- General Manifestations: fever, diarrhea, anorexia, and abdominal pain, juandice (liver-specific symptoms)
- Elevated Ig, ALT, AST, Bilirubin levels
A single-stranded RNA virus.
Viral antigen found in Serum, Stool, and Liver (fecal-oral transmisssion)
Incubation period: 15-60 days
No Chronic State associated with this strain
Most common in children and yound adults IgM antibodies appear in the acute stage but diminish within several weeks, followed by the development of protective IgG antibodies appear in the late / chronic state of disease, which persist usually for life.
- Hepatitis A virus (HAV)
- Diagnosis: IgM antibody detection
A double-stranded DNA virus
Associated with infective Dane particle
Transmission: Blood and Body Fluid
Incubation period: 45-180 days
Has a Chronic State associated with this strain
- Hepatitis B virus (HBV) - chronicity is more prevalent than in HCV strain
- Diagnosis: HBsAg in serum
Associated with Hepatitis B
Associated with a viral surface coat on Dane particles
Presence in serum is usually first evidence of Acute HBV and implies infectivity of blood.
Incubation period: 1-6 weeks
It's antibody counterpart appears weeks to months later
It's detection indicates past HBV infection and relative immunity.
- HBsAg (Hepatitis B surface Antigen)
Associated with Hepatitis B
Associated with a viral core on in Dane particles
Found in infected liver cells but undetectable in serum / blood; biopsy is best route
Acute infection - IgM predominates
Chronic infection - IgG predominates
- HBcAg (Hepatitis B core Antigen)
Associated with Hepatitis B
1. Found only in HBsAg-positive serum
2. Reflects more viral replication, greater infectivity of the blood and a greater likelihood of progression to chronic liver disease
3. Antibodies against this points to relatively lower infectivity and usually indicates a benign outcome (better prognosis).
- HBeAg (Hepatitis B e Antigen)
A single-stranded RNA virus
Transmission: Blood and Body Fluid
Incubation period: 14-160 days
Has a Chronic State associated with this strain
Highest likeliness of Chronic States (75+%)
Can be obtained through medical procedures (i.e. transfusions (80%), surgery)
- Hepatitis C virus (HCV)
- Diagnosis: anti-HCV serum antibody
A single-stranded defective-RNA virus
Transmission: Blood and Body Fluids
Incubation period: 30-180 days
Has a Chronic State associated with this strain
Must have HBV to get this strain
Hepatitis D virus (HDV)
A single-stranded RNA virus
Transmission: Waterborne (Fecal-Oral route)
Incubation period: 15-60 daysSevere forms possible in pregnant women (which can lead to death)
No Chronic State associated with this strain
Typically found in developing countries
Must have HAV to get this strain
Hepatitis E virus (HEV)
What is the most common type of primary liver cancer?
- Hepatocellular Carcinoma
- HBV is largely responsible
- Fungal Aflatoxins has a factor
- Chronic HCV has a factor
- α-FP in serum
- Ultrasound, CT, MRI
- Liver biopsy
- Prognosis and Treatment: Surgical Resection is best but only in some cases. Death often occurs in a few months
- Radioactivity / Chemotherapy usually unsucessful
Metastatic cancer is the most common hepatic malignancy (from elsewhere: lung, breast, colon, pancreas, stomach)
Formation or presence of calculi (gallstones) in the gallbladder. Cholesterol is the major contributing factor to this condition (bile can not compensate for the excess cholesterol leading to formation of these)
- Factors include:
- 1. Female sex
- 2. Obesity
- 3. Increased age (over 40-50 years)
- 4. Western Diet (high protein, low fiber)
- 5. Family History
- Signs / Symptoms: mostly asymptomatic
- Stones may traverse the cystic duct with or without symptoms of obstruction (persistent obstruction leads to inflammation
- Roller coaster ride of pain (pain increasing and decreasing for several hours)
- Nausea & Vomiting
- Pain in epigastrium / Right upper quandrant (liver region) radiating to the right lower scapula
- Diagnosis: Ultrasound
A chronic systemic autoimmune disease that primarily involves the joints
- Rheumatiod Arthritis (nodules develop in ~30% of patient with this RA)
- Peripheral Joints: (i.e. wrists, metacarpophalangeal joints) are symmetrically inflamed (synovial fluid (10K-50K WBCs/μLis turbid, yellow and sterile), leading to progressive destruction of articular structures (leading to degeneration) usually accompanied by systemic symptoms
- Precise cause is unknown; a genetic predisposition has been identified, environmental factors / geographic location may play a role
- Immune complexes (Type III Sensitivity) produced by synovial lining cells and in inflamed blood vessel. Plasma cells produce antibodies (rheumatiod factor (RF)) that contribute to these complexes
- Elevated ESR (erythrocyte sedimentation rate) and C-reactive protein indicate inflammations
- Sign / Symptoms: Insidious onset, often beginning with systemic joint symptoms (primarily affecting small joints such as in the hands and feet - can affect large joints but rare; general fatigue; morning stiffness lasting over 60 mins; low-grade fever (whole body)
- Diagnosis: Serum RF / anti-cyclic citrullinated peptide antibody (anti-CCP antibody - 70% of RA patients have antibodies to human y-globulin however, SLE patients will test positive for this as well), X-rays
How to diagnose a patient with RA?
- Must have at least 4 of the following and must be present for at least 6 weeks
- Arthritis of 3+ joints
- Arthritis of hand joints
- Morning stiffness for over an 1+ hours
- Rheumatoid nodules
- Systemic Arthritis
- Imaging changes (i.e. X-ray)
- Serum RF (positive in <5% of cases)
What disorders can simulate RA?
- Crystal-induced arthritis (Gout)
- SLE (Systemic Lupus Erythematosus)
This releases inflammatory mediators, which erode cartilage, subchondral bone, articular capsule, and ligaments?
- Hyperplastic synovial tissue / pannus
There are several common forms of fixed deformities in RA. Please identify?
The most common joint disorder, often becomes symptomatic in the 40s-50s and is nearly universal by age 80.
A chronic arthropathy characterized by disruption and potential loss of joint cartilage along with other joint changes, including some hypertrophy (osteophyte formation). Symptoms include gradually developing pain aggravated or triggered by activity, stiffness < 30 mins of awakening and after inactivity.
- Osteoarthritis (OA) / Degenerative Joint Disease (affecting older people)
- Pathophysiology: microfractures plus tissue growth leads to osteophytes / bone spurs entering the articular surface
- Subchondral bone stiffens, then undergoes infarction, and develops subchondral cysts. Attempts to repair causes subchondral sclerosis and osteophytes at joint margins
- Sign / Symptoms: Beginning with one or a few joints desribed as a deep ache. Pain worse on weight bearing, but eventually will become constant. Stiffness follows awakening or inactivity but lasts < 30 mins and lessens with movement.
- Lab Findings:
- Not triggered through inflammation
- WBC count low / normal
- Blood work
- RA - negative
- RF - negative
- ESR Normal
- Anti-CCP - negative
- Imaging: X-ray may not detect; may show articular destruction; density of bone by bone spur location
There are two kinds of OA, what are they and what are differences?
- Primary (Idiopathic) OA: Localized in certain joints
- Secondary OA: trauma, congential joint abnormalities, metabolic defects, endocrine and neuropathic diseases
A chronic, multisystem, inflammatory disorder of autoimmune etiology occurring predominantly in young women (70-90%). In genetically predisposed people, environmental triggers that cause autoimmune reactions.
Common symptoms: arthritis, malar and other skin rashes; ascites; pleuritis or pericarditis; renal or CNA involvement; hematologic cytopenia
- Systemic Lupus Erythmatosus (SLE)
- Joint symptoms: intermittent arthralgias to acute polyarthritis (90% of all cases)
- Most polyarthritis is nondestructive and nondeforming
- Skin and mucosal symptoms: malar butterfly erythema (color change /w protrusion), asbsence of papules and pustules helps distinguish SLE from rosacea; firm, maculopapular lesions (color change /w no protrusion), exposed areas of the face
- Cardiopulmonary symptoms: recurrent pleurisy / -itis, pericarditis, myocarditis
- Adenopathy and splenic symptoms: Splenomegaly (10%) leading to cytopenia
- Neurologic symptoms: Mild headaches, personality changes, ischemic stroke, subarachnoid hemorrhage, seizures, psychoses
- Renal symptoms: chronic glomerulitis, proteinuria
- Obstetric symptoms: miscarriage
- Hemoatologic symptoms: anemia, leukopenia, thrombocytopenia
- Diagnosis: broad spectrum cytopenia, autoantibodies / serum markers
- Lab findings: Antinuclear antibodies (ANA) / florescent test, positive for this in high titers > 1:80 occur in > 98% of patients
- Anti-double-stranded DNA antibodies (checked if positive for ANA)
- Tests for broad-spectrum cytopenia
- Serum complement (C3, C4) often depressed in active disease
- ESR is elevated frequently during disease
- Urinalysis: checked for RBCs, WBCs suggest active nephritis
- Prognosis: 10-yr survival in most developed countries > 95%
- Treatment: Corticosteriods and immunosuppressants for severe disease
What is the criteria to classify a patient as having SLE?
- At least 4 of these are required (but not necessarily)
- Malar rash
- Discoid rash
- Oral ulcers
- Serositis (pleuritis, pericarditis, ascites)
- Renal disorder
- Leukopenia < 4000/μL, lymphopenia < 1500/μL, thrombocytopenia < 100,000/μL
- Neurologic disorder
- Positive test for anti-DNA, anti-Smith, antiphospholipid antibodies
- ANA in high titers
A progressive metabolic bone disease that decreases bone density, skeletal weakness leads to fractures particularly in the thoracic and lumbar spine (T6-T8), wrist, and hip, acute or chronic back pain common
- Primary type (due to increased bone destruction): women postmenopause (95%), eldery men (~80%); estrogen def, decreased Ca intake, low Vit D levels, secondary hyperparathyroidism (parathyroid produces osteoclasts) contribute to primary type
- Risk Factors:
- 1. Estrogen def
- 2. Underweight = lower bone density
- 3. Physical inactivity
- 4. Smoking
- 5. Family history
- 6. Insufficient dietary intake of Ca, P and Vit D
- Symptoms: asymptomatic til fracture
- Diagnosis: Dual-energy X-ray absorptiometry (DEXA) for all women > 50
Precipitation of monosodium urate crystals into tissue, usually in and around joints, most often causing recurrent acute or chronic arthritis. Acut arthritis is initially monarticular and often involves the "big toe" / podagra.
- Symptoms: acute pain (primarily and at night), tenderness, warmth, redness, swelling, tense, shiny, purplish, fever, tachycardia, chills, and malaise
- Risk factors: hyperuricemia (urate levels elevate due to decreased excretion, increased production, increased purine intake), acute gouty arthritis may be triggered by trauma, infections, purine-rich food or alcohol
- Chronic gout can lead to Tophi
- Diagnosis: crystals in synovial fluid
In cases of Acute Infectious Arthritis (usually bacterial), what is the course of treatment?
Intravenous antibiotics and drainage of pus from joints
How to diagnose a patient with Bone and Joint tumors?
- Persistent or progressive unexplained pain
- MRI / CT
- Bone Scan
- Children often have primary and benign tumorsAdults > 40 often have metastatic tumors more common than primary malignant
Benign adenomatous hyperplasia of the perurethral prostate gland, causing variable degrees of bladder outlet obstruction.
50% of men 51-60 and >80% of men > 80
- Benign Prostatic Hyperplasia / Hypertrophy (BPH): may be due to hormonal changes assoc. /w aging
- Symptoms: urinary frequency, urgency, nocturia, decreased size and force of the urinary system produce hesitancy and intermittency
- Diagnosis: Serum PSA elevated (30-50% of patients)
A syndrome characterized pathologically by diffuse inflammarotry changes in the glomeruli adn clinically by abrupt-onset hematuria with RBC/WBC casts, and, often, hypertension, edema, and azotmia (elevated BUN and Creatinine)
Most common in children > 3 and in young adults
Lesions of glomeruli become enlarged and hypercellular
- Acute Nepthritic Syndrome / Acute Glomerulonephritis / Postinfectious Glomerulonephtitis (think infection)
- group A β-hemolytic streptococci
- Symptoms: hematuria (50% of cases), oliguria, edema, hypertension, renal failure
- Diagnosis: Antistreptolysin-O (ASO) best indicator of URIs; C3, C4 diminished during active disease
- Prognosis: usually good if initial renal damage in not severe and the source of antigenemia can be reduced or removed
A predictable complex that results from a severe, prolonged increase in glomerular permeability for protein.
Most common age 1.5-4 yrs
- Nephrotic Syndrome (think proteinuria)
- Symptoms: frothy urine due to protein, focal edema (trouble breathing)
- Complications: severe proteinuria, protein malnutrition
- Lab findings: proteinuria > 2g/m2/day, hypoalbuminemia
The most common bacterial infection in all age groups.
Amoung patients 20-50 yrs. Fiftyfold greater in women.
E. coli most common bacterium isolated and account for 80% of community-aquired infections
- UTI (Urinary Tract Infection)
- Cystitis: bladder inflammation, frequent urgent burning painful turbid urination; body fever
- Prevention: voiding after intercourse, cranberry juice reduce bacteria
What is the term for inflammation of urethra?
What is the term for inflammation of bladder?
What is the term for inflammation of prostate?
What is the term for inflammation of the outlet of the kidney?
The clinical condition resulting from chronic derangement and insufficiency of renal excretory and regulatory function (uremia).
Low GFR (glomerular filtration rate) indicate increase plasma concentrations of creatinine and urea
- Chronic Renal Failure (CRF)
- Endstage: diabetic nephropathy, hypertensive nephroangiosclerosis (hypertension)
- Symptoms: elevated BUN and creatinine; nocturia
- Dialysis helps
The process of removing toxins directly from the blood (hemodialysis)