Damjanov Chapter 3

Question 1

Hereditary hemochromatosis is a common ____ disorder marked by ____ storage caused by abnormal absorption of what where? What are many of the cases due to?

Answer 1

Autosomal recessive; iron; iron in the intestines;

mutations of the HFE gene

Question 2

HFE gene is linked to what locus on which chromosome? What is the mutation?

Answer 2

HLA-A locus on short arm of chromosome 6;

cysteine-to-tyrosine substitution at aa 282

Question 3

Activity of DMT-1 and ferroportin is normally suppressed by what? In hereditary hemochromatosis, levels of this are high or low?

Answer 3

Hepcidin; low

Question 4

What primes transferrin and HFE gene product for iron absorption via enterocytes?

Answer 4

Transferrin sensor cells

Question 5

Excess iron can (3):

Answer 5

1. excreted in the urine
2. aggregate into hemosiderin granules
3. formation of free radicals (inactivate enzymes involved in oxidative respiration, protein syntehsis, transmembrane transport; fibrosis; carcinogenesis because of potential DNA mutations made)

Question 6

In the liver, iron accumulates in what three things? Deposits of iron pigment lead to ____, gradually progressing to frank _____. Clinically what are the changes?

Answer 6

Kupffer cells, hepatocytes, bile duct cells;
fibrosis, cirrhosis;
hepatomegaly, portal hypertension with splenomegaly, esophageal varices (HEP)

Question 7

For HH, what color does the skin turn? What are two reasons why?

Answer 7

Brown;

accumulation of hemosiderin in macrophages and accumulation of melanin in epidermis

Question 8

Endocrine gland consequences of HH? Where else can HH affect?

Answer 8

Diabetes (accumulation of hemosiderin in pancreas), thyroid, gonads, also testicular atrophy and reduced testosterone;
Joints: calcification of synovium and deposits of hemosiderin causing joint injury (2nd, 3rd MCP joints in particular); iron in myocardium leading to cardiomyopathy, heart dilatation, conduction problems

Question 9

In HH, what happens to total plasma iron, transferrin sat, serum ferritin, urinary iron excretion?

Answer 9

They all go up

Question 10

Tests for HH are performed as a ______ to avoid what? Deposits of ____ in the liver can be estimated subjectively via what? What provides the final diagnosis of HH?

Answer 10

battery; false positives and negatives;
iron; livery biopsy stained with Prussian blue reacting with HEMOSIDERIN;
Genetic testing

Question 11

Hyperuricemia is defined empirically as

Answer 11

an elevation of uric acid conc in blood over 7 mg/dL

Question 12

T/F: if you have hyperuricemia, you have a high prob of developing gout?

Answer 12

False: 90% of persons with hyperuricemia won’t develop gout

Question 13

Although breakdown of ____ occurs in all tissues, ____ is produced only in organs, like the ____ and _____, that contain xanthine oxidoreductase

Answer 13

nucleic acids; uric acid; liver and intestines;

Question 14

Uric acid is derived how? How is it eliminated?

Answer 14

1. 2/3 derived from purine degradation; remaining third comes from diet
2. 2/3 of uric acid eliminated from blood in urine, and remaining 1/3 through intestines

Question 15

Solubility of ____ decreases at low temp, accounting for deposition of ____ in what tissue?

Answer 15

monosodium urate; urate crystals; joint tissue of big toe

Question 16

List ways that uric acid is overproduced? Underexcreted?

Answer 16

1. Primary: think Lesch-Nyhan
2. Secondary: tumor lysis syndrome after chemo (release of purines); leukemia, lymphoma, chronic hemolytic anemia can cause hyperuricemia);
3. excrete <700 mg of uric acid/day, like chronic renal disease
4. Drugs (e.g. thiazides, aka diuretics); levodopa and cytclosporine
5. Toxins: e.g. lead, affecting uric acid excretion in proximal tubules
6. Metabolic disturbances: lactic acidosis, hyperparathyroidism, hypothyroid

Question 17

Traces how hyperuricemia leads to tissue injury: steps

Answer 17

1. Hyperuricemia from overproduction or underexcretion
2. Microtophus formation (MS phosphate deposits)
3. Release of monosodium urate crystals
4. Chemotaxis and irritation of the joint
5. Neutrophil exudation (make oxygen radicals, arachidonic acid derivatives, cytokines)
6. Phagocytosis of crystals
7. Release of lysosomes and mediators
8. Inflammation and tissue injury

Question 18

Where can gout form due to MSU deposition?

Answer 18

Pinna of ear, elbow, kidneys, fingers, infrapatellar tendon, Achilles, big toe (podagra)

Question 19

Prolonged hyperuricemia can affect function of what? What are formed in acid urine?

Answer 19

Renal tubules; uric acid stones

Question 20

Effects of alcohol in dose dependent manner:

Answer 20

1. Sedation (50 mg/dL)
2. Loss of motor coordination (50-150 mg/dL)
3. Delirium (150-200 mg/dL)
4. Unconsciouness and coma or respiratory arrest (300-400 mg/dL)

Question 21

Three ways to metabolize alcohol in liver cells:

Answer 21

1. CYP2E (liver SER)
2. Alcohol DH
3. Catalase in peroxisomes

Question 22

Increased ratio of NADH/NAD means what?

Answer 22

1. Lactic acidosis
2. hypoglycemia
3. Beta oxidation of fatty acid reduced and triglycerid formation enhanced, leading to fatty change in liver cells (could progress to steatohepatitis and then cirrhosis)

Question 23

Someone who is a chronic alcohol drinker typically associated with ____, and without alochol, they can develop what? Symptoms of this?

Answer 23

tolerance; alcohol withdrawal syndrome;

the shakes, perhaps delirium tremens, seizures, and death

Question 24

Chronic alcoholics have a deficiency in what nutrient and what are the symptoms you might see?

Answer 24

B1 (thiamine):

1. Wernicke’s (confusion, ophthalmoplegia, nystagmus, ataxia, and peripheral sensory-motor neuropathy)
2. Peripheral neuropathy
3. Korsakoff’s psychosis (amnesia, inability to learn, confabulation)

Question 25

Chronic alcohol intake can have adverse effects on

Answer 25

skeletal muscle (rhabdomyolysis with increased CK, and renal tubular necrosis) and heart (cardiomyopathy and you see beri-beri heart; tachycardia could ensue with a holiday heart)

Question 26

Cardiogenic shock can be caused by what?

Answer 26

1. Decreased preload (venous return of blood in RA reduced) 2. Mech obstruction of venous return (e.g. thromboemboli of pulmonary veins and tension pneumothorax) 3. Impaired diastolic dilatation of the ventricles (pericardial tamponade, ventricular tachyarrhythmia, hypertrophic cardiomyopathy 4. Contractile insufficiency: Pump failure occurring with MI, myocarditis, dilated cardiomyopathy 5. Valvular obstruction: increased afterload 6. Valvular insufficiency: incomplete closure of valves

Question 27

Hypovolemic shock can occur due to what?

Answer 27

1. Bleeding 2. Fluid loss (ECF due to e.g. severe body burns) 3. Pooling of fluid in intestines (paralytic ileus or intestinal volvulus) 4. Pooling of fluid in body cavities (ascites and hydrothorax) 5. Anasarca (increased vascular perm with septic or anaphylactic shock)

Question 28

Distributive shock results from ____, increasing the ___ of the vascular system; list causes

Answer 28

vasodilation; capacitance; 1. sepsis: SIRS, with TNF, IL, NO, acting on vessels to cause their dilation and leading to pooling of blood in peripheral circulation 2. Anaphylactic shock: type I hypersens reaction to foreign proteins (substances released from mast cells coated with IgE) 3. Neurogenic shock (brain trauma and intracranial hemorrhage) 4. Drugs (vasoactive drugs can cause massive dilation)

Question 29

Shock leads to multiple organ failure, including what manifestations?

Answer 29

1. DIC 2. Diffuse alveolar damage of ARDS (lungs edematous and show widespread deposits of fibrin along alveolar lining) 3. Renal tubular necrosis: low urinary output 4. Centrolobular necrosis of liver (increased AST and ALT) 5. Iscehmic necroses in myocardium: hypoperfusion of the heart and later pump failure 6. Edema and focal ischemic changes in the brain

Question 30

For HIV and acute retroviral syndrome, what does this entail?

Answer 30

Abs to HIV-related antigen gp120 by ELISA after 12 weeks;

Question 31

In latency phase of HIV, what could develop?

Answer 31

1. Lymphadenopathy 2. Mucocutaneous infections (genital or oral herpes, VZV, hairy leukoplakia) 3. Skin diseases (seborrheic dermatitis and psoriasis) 4. Bacterial pneumonia (strep pneumoniae)

Question 32

AIDS dominated by what?

Answer 32

1. CNS (HIV encephalophathy with dementia and maybe low pressur hydrocephalus, aseptic meningitis, opportunistic infections like Toxoplasma, CMV, cryptococcus, TB, and lastly peripheral neuropathy) 2. Repiratory system: think pneumocystis jiroveci, TB, candida, aspergillus flavus, blastomyces dermtitidis 3. GI: Can see N/V, oral infections like herpes labialis and herpes simplex virus, thrush, hairy leukoplakia, esophagitis, diarrhea (M avium intra, cryptosporidium, Giardia, campylobacter, C diff), and liver disease 4. Hematopoietic and lymphoid systems: lymph node enlargement, TAL, lymphoma 5. Skin: itching, maybe cat-scratch disease, HSV, HPV leading to warts, Kaposi's sarcoma

Question 33

In SLE, what are the most common sites of immune complex deposition?

Answer 33

Glomerular basement membranes, serosal surfaces of thoracic and abdo organs, synovial membranes of the joints, choroid plexus of lateral cerebral ventricles, or choroids of the eyes

Question 34

In SLE, what do cytotoxic antibodies target? How else can they be cytotoxic mechanistically?

Answer 34

RBC's, leukocytes, platelets, or endothelial cells; | can activate complement and kill cells through complement-mediated mechs or facilitating cell destruction by macrophages

Question 35

Patterns in which antibodies can bind to nuclear antigens as seen in SLE:

Answer 35

1. Diffuse pattern: entire nucleus stains due to nonselectivity with nucleic acid and protein of chromatin 2. Speckled pattern: Ab's bind proteins like histones and ribonucleoproteins 3. Rim pattern: e.g. ds DNA

Question 36

Secondary antiphospholipid Ab syndrome due to what?

Answer 36

Lupus anticoagulant (antiphospholipid antibodies react with phospholipids complexed plasma proteins)

Question 37

SLE can be monitored by decreased what, and appearance of what in the urine?

Answer 37

Complement; | RBCs, RBC casts, WBC casts, and increased serum concentration of BUN and creatinine

Question 38

Most lung cancers originate from ___ and are called ____; How do lung cancers usually metastasize?

Answer 38

bronchial epi; bronchogenic; | To local lymph nodes and hematogenous metastases lead to brain, liver, bones, and often adrenal glands

Question 39

Signs and symptoms of lung cancer are:

Answer 39

1. Cough (bronchial inflammation and irritation of nerve endings in bronchi) 2. Dyspnea: major bronchi obstructed; 3. Chest pain: compression of nerve endings in pleura or major nerves, like Pancoast or Horner's 4. Weightloss, fatigue, anorexia 5. Fever: inflammation occurring in bronchi due to irritation by tumor 6. Hemoptysis 7. Clubbing of fingers (hypertrophic pulmonary osteoarthropathy) 8. Hoarseness: compression of left recurrent laryngeal nerve 9. SVC syndrome: compression of SVC by mediastinal extension or lymph node invovement 10. Hepatomegaly, bone pain, neurologic symptoms

Question 40

Most common endocrine paraneoplastic syndromes in patients with small-cell carcinoma are...; common finding is squamous cell carcinoma is

Answer 40

SIADH, Cushing's, Lambert-Eaton; PTHrP

Question 41

Patients with radiological examination is essential for

Answer 41

diagnosis of lung cancer as well as for its staging and follow-up after treatment, and need to secure diagnosis by biopsy and pathologic examination